text:
[18F]-fluoride positron emission tomography for imaging condylar hyperplasia.
Laverick, S; Bounds, G; Wong, Wai Lup
The management of condylar hyperplasia depends on the diagnosis of continued growth in the affected condyle, and there is currently no satisfactory way of imaging it. [(18)F]-fluoride positron emission tomography (PET) was included in the investigation of 5 patients who were suspected of having condylar hyperplasia, and the results were correlated with the operative findings. The technique correctly identified condylar hyperplasia in all patients. Our results suggest that [(18)F]-fluoride PET is a valid way of assessing patients with condylar hyperplasia. PMID:18926607
Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis
Cartlidge, Timothy R.G.; Jenkins, William S.A.; Adamson, Philip D.; Robson, Phillip; Lucatelli, Christophe; Van Beek, Edwin J.R.; Prendergast, Bernard; Denison, Alan R.; Forsyth, Laura; Rudd, James H.F.; Fayad, Zahi A.; Fletcher, Alison; Tuck, Sharon; Newby, David E.; Dweck, Marc R.
Background— 18F-Fluoride positron emission tomography (PET) and computed tomography (CT) can measure disease activity and progression in aortic stenosis. Our objectives were to optimize the methodology, analysis, and scan–rescan reproducibility of aortic valve 18F-fluoride PET-CT imaging. Methods and Results— Fifteen patients with aortic stenosis underwent repeated 18F-fluoride PET-CT. We compared nongated PET and noncontrast CT, with a modified approach that incorporated contrast CT and ECG-gated PET. We explored a range of image analysis techniques, including estimation of blood-pool activity at differing vascular sites and a most diseased segment approach. Contrast-enhanced ECG-gated PET-CT permitted localization of 18F-fluoride uptake to individual valve leaflets. Uptake was most commonly observed at sites of maximal mechanical stress: the leaflet tips and the commissures. Scan–rescan reproducibility was markedly improved using enhanced analysis techniques leading to a reduction in percentage error from ±63% to ±10% (tissue to background ratio MDS mean of 1.55, bias −0.05, limits of agreement −0·20 to +0·11). Conclusions— Optimized 18F-fluoride PET-CT allows reproducible localization of calcification activity to different regions of the aortic valve leaflet and commonly to areas of increased mechanical stress. This technique holds major promise in improving our understanding of the pathophysiology of aortic stenosis and as a biomarker end point in clinical trials of novel therapies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026. PMID:27733431
Bone metabolic activity measured with positron emission tomography and [[sup 18]F] fluoride ion in renal osteodystrophy: Correlation with bone histomorphometry
Messa, C.; Goodman, W.G.; Hoh, C.K.; Choi, Y.; Nissenson, A.R.; Salusky, I.B.; Phelps, M.E.; Hawkins, R.A. )
The authors evaluated the bone metabolic activity in patients with renal osteodystrophy using positron emission tomography and [[sup 18]F] fluoride ion. Eight patients had secondary hyperparathyroidism (HPT), and three had low-turnover bone disease. Eleven normal subjects were also studied, and three of the eight HPT patients were reevaluated after therapy. A rate constant (K) describing the net transport of [[sup 18]F] fluoride ion into a bound compartment in bone was calculated using both a three-compartment model and Patlak graphical analysis. Values of K were compared with biochemical data and with histomorphometric indices. The results indicate that K is significantly higher (P < 0.01) in HPT patients than in normal subjects and patients with low-turnover bone disease. Values of K correlated with serum alkaline phosphatase (r = 0.81) and PTH (r = 0.93) levels and with histomorphometric indices of bone formation rate (r = 0.84, P < 0.01) and eroded perimeter (r = 0.77, P < 0.05). Values of K decreased by 40 and 30%, respectively, in two patients who underwent parathyroidectomy and medical therapy. Positron emission tomography studies of bone using [[sup 18]F] fluoride ion can differentiate low turnover from high turnover lesions of renal osteodystropy and provide quantitative estimates of bone cell activity that correlate with histomorphometric data.
Calcified peritoneal metastasis identified on 18F-fluoride positron emission tomography/computed tomography: Importance of extraosseous uptake of F-18 fluoride
Verma, Priyanka; Chandra, Piyush; Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Rangarajan, Venkatesh
F-18 NaF positron emission tomography/computed tomography (PET/CT) is used for the evaluation of malignant and nonmalignant osseous disease. Extraosseous uptake of 18 fluoride-NaF has been observed in the arterial vasculature, gastrointestinal tract, and genitourinary tract. We describe a case of a woman with carcinoma of unknown primary in whom F-18 NaF PET/CT showed tracer uptake in the calcified peritoneal metastasis. Extraosseous findings on F-18 NaF PET/CT, though rare, may be visualized and may result in important management changes. PMID:27095869
Magnetic Droplet Microfluidics as a Platform for the Concentration of [18F]Fluoride and Radiosynthesis of Sulfonyl [18F]Fluoride.
Fiel, Somewhere A; Yang, Hua; Schaffer, Paul; Weng, Samuel; Inkster, James A H; Wong, Michael C K; Li, Paul C H
The radioisotope 18F is often considered the best choice for positron emission tomography (PET) owing to its desirable chemical and radiochemical properties. However, nucleophilic 18F-fluorination of large, water-soluble biomolecules, based on C-F bond formation, has traditionally been difficult. Thus, several aqueous fluorination approaches that offer significant versatility in radiopharmaceutical synthesis with sensitive targeting vectors have been developed. Furthermore, because 18F decays rapidly, production of these 18F-labeled compounds requires an automated process to reduce production time, reduce radiation exposure, and minimize losses due to the transfer of reagents during tracer synthesis. Herein, we report the use of magnetic droplet microfluidics (MDM) as a means to concentrate [18F]fluoride from the cyclotron target solution, followed by the synthesis of an 18F-labeled compound on a microfluidic platform. Using this method, we have demonstrated 18F preconcentration in a small-volume droplet through the use of anion exchanging magnetic particles. By using MDM, the preconcentration step took approximately 5 min, and the [18F]fluoride solution was preconcentrated by 15-fold. After the preconcentration step, an 18F-labeling reaction was performed on the MDM platform using the S-F bond formation in aqueous conditions to produce an arylsulfonyl [18F]fluoride compound which can be used as a prosthetic group to label PET targeting ligands. The high radiochemical purity of 95±1% was comparable to the 96% previously reported using a conventional method. In addition, when MDM was used, the total synthesis time was improved to 15 min with lower reagent volumes (50-60 μL) used.
Retention of [(18)F]fluoride on reversed phase HPLC columns.
Ory, Dieter; Van den Brande, Jeroen; de Groot, Tjibbe; Serdons, Kim; Bex, Marva; Declercq, Lieven; Cleeren, Frederik; Ooms, Maarten; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy
As [(18)F]fluoride is a starting reagent in the radiosynthesis of most fluorine-18 labeled positron emission tomography (PET) tracers, its chromatographic behavior on reversed phase (RP) HPLC columns is important for the purification performance and accuracy of RP HPLC quality control methods. We have investigated the chromatographic behavior and recovery of [(18)F]fluoride as a function of the type and brand of RP HPLC column, the pH and the composition of the mobile phase. Elution and elution profile of [(18)F]fluoride from six RP-HPLC columns (Waters XBridge C18 3 mm × 100 mm 3.5 μm; Grace Platinum EPS C18 4.6 mm × 100 mm, 3 μm; Waters XTerra C18 4.6 mm × 250 mm, 5 μm; Phenomenex C18 4.6 mm × 150 mm, 5 μm; Hamilton PRP-1 column 4.1 mm × 150 mm, 5 μm; Merck KGaA Chromolith Performance C18 3 mm × 100 mm) eluted with mobile phase composed of phosphate or acetate buffers (pH 2, 3, 4, 5, 7.3 and 9) and acetonitrile or ethanol as organic modifier were characterized. The elution profile was determined by on-line radioactivity measurement in the column eluate and recovery was calculated by comparison of radioactivity eluted with the HPLC column present or absent in the chromatographic flow path. Interestingly, [(18)F]fluoride recovery increased with increasing pH. At pH 3 all packed silica-based columns showed significant retention of fluorine-18, whereas almost no retention was observed on a polymeric PRP-1 column. However at pH 5, [(18)F]fluoride recovery was above 90% for each tested column. In addition, small differences were observed when changing the composition of the mobile phase. We therefore recommend to use a mobile phase with pH > 5 for silica based C18 columns for both quality control and semi-preparative HPLC of fluorine-18 labeled PET radiopharmaceuticals. If required a lower pH can be used in combination with a polymer based HPLC column.
Clinical utility of (18)F-fluoride PET/CT in benign and malignant bone diseases.
Li, Yuxin; Schiepers, Christiaan; Lake, Ralph; Dadparvar, Simin; Berenji, Gholam R
(18)F labeled sodium fluoride is a positron-emitting, bone seeking agent with more favorable skeletal kinetics than conventional phosphate and diphosphonate compounds. With the expanding clinical usage of PET/CT, there is renewed interest in using (18)F-fluoride PET/CT for imaging bone diseases. Growing evidence indicates that (18)F fluoride PET/CT offers increased sensitivity, specificity, and diagnostic accuracy in evaluating metastatic bone disease compared to (99m)Tc based bone scintigraphy. National Oncologic PET Registry (NOPR) has expanded coverage for (18)F sodium fluoride PET scans since February 2011 for the evaluation of osseous metastatic disease. In this article, we reviewed the pharmacological characteristics of sodium fluoride, as well as the clinical utility of PET/CT using (18)F-fluoride in both benign and malignant bone disorders.
A Transmetalation Reaction Enables the Synthesis of [18F]5-Fluorouracil from [18F]Fluoride for Human PET Imaging
Translation of new 18F-fluorination reactions to produce radiotracers for human positron emission tomography (PET) imaging is rare because the chemistry must have useful scope and the process for 18F-labeled tracer production must be robust and simple to execute. The application of transition metal mediators has enabled impactful 18F-fluorination methods, but to date none of these reactions have been applied to produce a human-injectable PET tracer. In this article we present chemistry and process innovations that culminate in the first production from [18F]fluoride of human doses of [18F]5-fluorouracil, a PET tracer for cancer imaging in humans. The first preparation of nickel σ-aryl complexes by transmetalation from arylboronic acids or esters was developed and enabled the synthesis of the [18F]5-fluorouracil precursor. Routine production of >10 mCi doses of [18F]5-fluorouracil was accomplished with a new instrument for azeotrope-free [18F]fluoride concentration in a process that leverages the tolerance of water in nickel-mediated 18F-fluorination. PMID:27087736
Analysis of bone mineralization on uncemented femoral stems by [18F]-fluoride-PET
Purpose We present the first study using fluoride-positron emission CT (F-PET/CT) to analyze mineralization of bone in the femur adjacent to uncemented stems following total hip arthroplasty (THA). We studied patients who were operated bilaterally for osteoarthritis with 2 different stems during the same surgical session. Patients and methods THA was performed bilaterally during the same surgical session in 8 patients with bilateral osteoarthritis of the hip. An SL-PLUS stem was inserted in one hip and a BetaCone stem was inserted in the contralateral hip, with randomization of side and sequence. A second group of 12 individuals with a normal healthy hip was used as reference for normal bone metabolism. Clinical and radiographic evaluation was performed preoperatively, postoperatively, and at 2 years. We used [18F]-fluoride-PET/CT to analyze bone mineralization adjacent to the stems 1 week, 4 months, and 12 months after surgery. We modified the Polar Map system to fit the upper femur for analysis and presentation of the PET results from 12 regions of interest adjacent to the whole stem. Results The clinical results were good at 2 years. By radiography, all stems were stable. At PET analyses 1 week after surgery, the activity was higher for the SL-PLUS group than for the BetaCone group. The activity was statistically significantly higher for both stems than the reference values at 4 months, and was most pronounced in the upper femur. At one year, the activity had declined more for the BC group than for the SL group. Interpretation The bone mineralization activity varied between different regions for the same stem and between different time periods for each group. F-PET/CT is a novel and valuable tool for analysis of bone mineralization patterns around uncemented femoral stems in detail. The combination of PET/CT analysis and the modified Polar Map system may provide a useful tool for future studies of metabolic bone responses to prosthetic implants. PMID:23506163
Fluorine-18 labeling of small molecules: the use of 18F-labeled aryl fluorides derived from no-carrier-added [18F]fluoride as labeling precursors.
Wuest, F
The favourable long-half life, the ease of production and the low energy of the emitted positron make 18F an ideal radionuclide for PET imaging. Radiochemistry of 18F basically relies on two distinctive types of reactions: nucleophilic and electrophilic reactions. All syntheses of 18F-labeled radiotracers are based on either [18F]fluoride ion or [18F]fluorine gas as simple primary labeling precursors which are obtained directly from the cyclotron. They can be applied either directly to the radiosynthesis or they can be transformed into more complex labeling precursors enabling the multi-step build-up of organic tracer molecules. The topic of this review is a survey on the application of several 18F-labeled aryl fluorides as building blocks derived from no-carrier-added (n.c.a.) [18F] fluoride to build up small monomeric PET radiotracers at high specific radioactivity by multi-step synthesis procedures.
[Bone scanning with sodium 18F-fluoride PET and PET/CT. German guideline Version 1.0.].
Hellwig, D; Krause, B-J; Schirrmeister, H; Freesmeyer, M
In nuclear medicine, bone scanning is based on the principle of scintigraphy using bone-seeking radiopharmaceuticals which accumulate in sites of increased bone formation. From a historical point of view, (18)F-fluoride was one of the first osteotropic tracers which was replaced by (99m)Tc-labelled polyphosphonates. With the development of modern PET equipment the superior diagnostic performance of (18)F-fluoride PET for the detection and characterization of osseous lesions was proven in comparison to conventional bone scanning. Recently, its importance as a substitute of conventional skeletal scintigraphy increased in a time with limited availability of (99)Mo/(99m)Tc. To ensure health care during this period, (18)F-fluoride PET currently became part of common outpatient care. This guideline comprehends recommendations on indications, protocols, interpretation and reporting of (18)F-fluoride PET and PET/CT. PMID:20838734
[(18)F]-Group 13 fluoride derivatives as radiotracers for positron emission tomography.
Chansaenpak, Kantapat; Vabre, Boris; Gabbaï, François P
The field of (18)F chemistry is rapidly expanding because of the use of this radionuclide in radiotracers for positron emission tomography (PET). Until recently, most [(18)F]-radiotracers were generated by the direct attachment of (18)F to a carbon in the organic backbone of the radiotracer. The past decade has witnessed the emergence of a new strategy based on the formation of an (18)F-group 13 element bond. This approach, which is rooted in the field of fluoride anion complexation/coordination chemistry, has led to the development of a remarkable family of boron, aluminium and gallium [(18)F]-fluoride anion complexing agents which can be conjugated with peptides and small molecules to generate disease specific PET radiotracers. This review is dedicated to the chemistry of these group 13 [(18)F]-fluorides anion complexing agents and their use in PET. Some of the key fluoride-binding motifs covered in this review include the trifluoroborate unit bound to neutral or cationic electron deficient backbones, the BF2 unit of BODIPY dyes, and AlF or GaF3 units coordinated to multidentate Lewis basic ligands. In addition to describing how these moieties can be converted into their [(18)F]-analogs, this review also dicusses their incorporation into bioconjugates for application in PET. PMID:26548467
Sultone opening with [18F]fluoride: an efficient 18F-labelling strategy for PET imaging.
Schmitt, Sébastien; Bouteiller, Cédric; Barré, Louisa; Perrio, Cécile
Sultones were subject to ring opening by nucleophilic attack with [(18)F]fluoride to afford easily purified (18)F-labelled hydrophilic sulfonated products in high yields. A two-step sequence including radiofluorination and coupling to lysine was then developed from a bis-sultone precursor as a model approach for the labelling of biopolymers.
Regularized ML reconstruction for time/dose reduction in 18F-fluoride PET/CT studies
NASA Astrophysics Data System (ADS)
De Bernardi, Elisabetta; Magnani, Patrizia; Gianolli, Luigi; Carla Gilardi, Maria; Bettinardi, Valentino
We are proposing a regularized reconstruction strategy for the detection of bone lesions in 18F-fluoride whole body PET images obtained with 1 min/bed using the anatomical information provided by co-registered CT images. Bones are recognized on CT images and then transposed into the PET volume framework. During PET reconstruction, two different priors are used for bone and non-bone voxels: the relative difference prior in bone and the P-Gaussian prior in non-bone. After a tuning of the priors' parameters, the reconstruction strategy has been tested on 6 18F-fluoride PET/CT studies, on a total of 67 lesions. Regularized images provided results comparable to the standard 3 min/bed images, in terms image quality, lesion activity, noise level and noise correlation. The proposed strategy therefore appears to be a useful tool to reduce the acquisition time or the injected dose in 18F-fluoride PET studies.
21-(/sup 18/F)fluoro-16 alpha-ethyl-19-norprogesterone: synthesis and target tissue selective uptake of a progestin receptor based radiotracer for positron emission tomography
Pomper, M.G.; Katzenellenbogen, J.A.; Welch, M.J.; Brodack, J.W.; Mathias, C.J.
We have synthesized 21-(/sup 18/F)fluoro-16 alpha-ethyl-19-norprogesterone (FENP), a high affinity ligand for the progesterone receptor, labeled with the positron-emitting radionuclide fluorine-18 (t1/2 = 110 min). The synthesis proceeds in two steps from 21-hydroxy-16 alpha-ethyl-19-norprogesterone and involves (/sup 18/F)fluoride ion displacement of the 21-trifluoromethanesulfonate (21-triflate). This material is purified by HPLC and is obtained in 4-30% overall yield (decay corrected) within 40 min after the end of bombardment to produce (/sup 18/F)fluoride ion. The effective specific activity, determined by competitive radioreceptor binding assays, is 700-1400 Ci/mmol. In vivo, (/sup 18/F)FENP demonstrates highly selective, receptor-mediated uptake by the uterus of estrogen-primed rats; the uterus to blood and uterus to muscle ratios were respectively 26 and 16 at 1 h and 71 and 41 at 3 h after injection. The high target tissue selectivity of this uptake suggests that this compound may be useful for the in vivo imaging of progestin target tissues and receptor-rich tumors (such as human breast tumors) by positron emission tomography.
Sodium 18F-Fluoride PET/CT of Bone, Joint and Other Disorders
Jadvar, Hossein; Desai, Bhushan; Conti, Peter S.
The use of 18F-sodium fluoride (18F-NaF) with positron emission tomography-computed tomography (PET/CT) is increasing. This resurgence of an old tracer has been fueled by several factors including superior diagnostic performance over standard 99mTc-based bone scintigraphy, growth in the availability of PET/CT imaging systems, increase in the number of regional commercial distribution centers for PET radiotracers, the recent concerns about potential chronic shortages with 99mTc based radiotracers, and the recent decision by the Centers for Medicare and Medicaid Services to reimburse for 18F-NaF PET/CT for evaluation of patients with known or suspected bone metastases through the National Oncologic PET Registry. The major goal of this article is to review the current evidence on the diagnostic utility of 18F-NaF in the imaging assessment of bone and joint in a variety of clinical conditions. PMID:25475379
No-carrier-added (NCA) aryl ([sup 18]F) fluorides via the nucleophilic aromatic substitution of electron rich aromatic rings
Yushin Ding; Fowler, J.S.; Wolf, A.P.
A method for synthesizing no-carrier-added (NCA) aryl [.sup.18 F] fluoride substituted aromatic aldehyde compositions bearing an electron donating group is described. The method of the present invention includes the step of reacting aromatic nitro aldehydes having a suitably protected hydroxyl substitutent on an electron rich ring. The reaction is The U.S. Government has rights in this invention pursuant to Contract Number DE-AC02-76CH00016, between the U.S. Department of Energy and Associated Universities Inc.
Positron Emission Tomography (PET)
Welch, M.J.
Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET. 22 figs.
Positron Emission Tomography (PET)
DOE R&D Accomplishments Database
Welch, M. J.
Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET.
Cardiac Positron Emission Tomography
Geltman, Edward M.
Positron emission tomography (PET) is a new technique for noninvasively assessing myocardial metabolism and perfusion. It has provided new insight into the dynamics of myocardial fatty acid and glucose metabolism in normal subjects, patients with ischemic heart disease and those with cardiomyopathies, documenting regionally depressed fatty acid metabolism during myocardial ischemia and infarction and spatial heterogeneity of fatty acid metabolism in patients with cardiomyopathy. Regional myocardial perfusion has been studied with PET using water, ammonia and rubidium labeled with positron emitters, permitting the noninvasive detection of hypoperfused zones at rest and during vasodilator stress. With these techniques the relationship between perfusion and the metabolism of a variety of substrates has been studied. The great strides that have been made in developing faster high-resolution instruments and producing new labeled intermediates indicate the promise of this technique for facilitating an increase in the understanding of regional metabolism and blood flow under normal and pathophysiologic conditions. ImagesFigure 5.Figure 6.Figure 7.Figure 8.Figure 9. PMID:3879048
Lameka, Katherine; Farwell, Michael D; Ichise, Masanori
Positron emission tomography (PET) is a minimally invasive imaging procedure with a wide range of clinical and research applications. PET allows for the three-dimensional mapping of administered positron-emitting radiopharmaceuticals such as (18)F-fluorodeoxyglucose (for imaging glucose metabolism). PET enables the study of biologic function in both health and disease, in contrast to magnetic resonance imaging (MRI) and computed tomography (CT), that are more suited to study a body's morphologic changes, although functional MRI can also be used to study certain brain functions by measuring blood flow changes during task performance. This chapter first provides an overview of the basic physics principles and instrumentation behind PET methodology, with an introduction to the merits of merging functional PET imaging with anatomic CT or MRI imaging. We then focus on clinical neurologic disorders, and reference research on relevant PET radiopharmaceuticals when applicable. We then provide an overview of PET scan interpretation and findings in several specific neurologic disorders such as dementias, epilepsy, movement disorders, infection, cerebrovascular disorders, and brain tumors. PMID:27432667
Positron emission mammography imaging
Moses, William W.
This paper examines current trends in Positron Emission Mammography (PEM) instrumentation and the performance tradeoffs inherent in them. The most common geometry is a pair of parallel planes of detector modules. They subtend a larger solid angle around the breast than conventional PET cameras, and so have both higher efficiency and lower cost. Extensions to this geometry include encircling the breast, measuring the depth of interaction (DOI), and dual-modality imaging (PEM and x-ray mammography, as well as PEM and x-ray guided biopsy). The ultimate utility of PEM may not be decided by instrument performance, but by biological and medical factors, such as the patient to patient variation in radiotracer uptake or the as yet undetermined role of PEM in breast cancer diagnosis and treatment.
An Investigation of (Diacetoxyiodo)arenes as Precursors for Preparing No-Carrier-Added [(18)F]Fluoroarenes from Cyclotron-Produced [(18)F]Fluoride Ion.
Haskali, Mohammad B; Telu, Sanjay; Lee, Yong-Sok; Morse, Cheryl L; Lu, Shuiyu; Pike, Victor W
Treatment of (diacetoxyiodo)arenes (1a-1u) with cyclotron-produced [(18)F]fluoride ion rapidly affords no-carrier-added [(18)F]fluoroarenes (2a-2u) in useful yields and constitutes a new method for converting substituted iodoarenes into substituted [(18)F]fluoroarenes in just two steps.
A critical study on borosilicate glassware and silica-based QMA's in nucleophilic substitution with [18F]fluoride: influence of aluminum, boron and silicon on the reactivity of [18F]fluoride.
Svadberg, A; Clarke, A; Dyrstad, K; Martinsen, I; Hjelstuen, O K
Leachables of borosilicate glassware and silica-based anion exchange columns (QMAs) may influence nucleophilic substitution with [(18)F]fluoride ([(18)F]F(-)). Aluminum, boron and silicon, all constituents of borosilicate glass, were found as water soluble leachables in a typical PET synthesis setup. Relevant ranges of the leachable quantities were studied based on an experimental design, in which species of the three elements were added to the labeling of the precursor for anti-1-amino-3-[(18)F]fluorocyclobutyl-1-carboxylic acid ([(18)F]FACBC). Levels of 0.4-2 ppm aluminum as AlCl(3) had a strong negative influence on labeling yield while 4-20 ppm of boron as KBO(2) and 50-250 ppm of silicon as Na(2)SiO(3) did not have a significant impact. Interesting interaction effects between the elements were observed, where particularly KBO(2) reduced the negative effect of AlCl(3) on labeling yield. It can be concluded that leachables of borosilicate glassware easily can influence nucleophilic substitution with n.c.a. [(18)F]F(-) and give variable yields.
Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with 18F positron emission tomography
Psaltis, Peter J.
Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of 18Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of 18Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) and sodium 18F-fluoride (18F-NaF). PMID:27500093
A broad overview of positron emission tomography radiopharmaceuticals and clinical applications: what is new?
Vallabhajosula, Shankar; Solnes, Lilja; Vallabhajosula, Brigitte
Positron emission tomography (PET)/computed tomography (CT) is a rapidly expanding imaging modality, thanks to the availability of compact medical cyclotrons and automated chemistry synthesis modules for the production of PET radiopharmaceuticals. Despite the availability of many radiotracers, [(18)F]fluorodeoxyglucose (FDG) is currently the most widely used radiopharmaceutical in PET, and the field of molecular imaging is anxiously awaiting the introduction of new PET radiopharmaceuticals for routine clinical use. During the last five years, several proprietary PET radiopharmaceuticals have been developed by major companies, and these new agents are in different stages of clinical evaluation. These new PET drugs are designed for imaging brain beta amyloid, myocardial perfusion, amino acid transport, angiogenesis, and tumor antigen expression. In addition, the National Cancer Institute, Society of Nuclear Medicine Clinical Trials Network, and the American College of Radiology Imaging Network have been conducting multicenter clinical trials with several nonproprietary PET drugs such as sodium [(18)F]fluoride, [(18)F]fluorothymidine, [(18)F]fluoromisonidazole, and (64)Cu-labeled diacetyl-bis (N(4)-methylthiosemicarbazone. All new PET radiopharmaceuticals, like any other drugs, must be manufactured under current good manufacturing practices as required by the Food and Drug Administration before clinical evaluation (phases I, II, and III) and submission of new drug application. This review briefly describes the chemistry, mechanisms(s) of localization, and clinical application of both proprietary and nonproprietary new PET drugs under multicenter clinical evaluation.
Imaging Prostate Cancer: An Update on Positron Emission Tomography and Magnetic Resonance Imaging
Turkbey, Baris; Choyke, Peter; Capala, Jacek
Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an essential role in the clinical management of patients. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information. Developments in imaging technologies, specifically magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT), have improved the detection rate of prostate cancer. MRI has improved lesion detection and local staging. Furthermore, MRI allows functional assessment with techniques such as diffusion-weighted MRI, MR spectroscopy, and dynamic contrast-enhanced MRI. The most common PET radiotracer, 18F-fluorodeoxyglucose, is not very useful in prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET/CT imaging of prostate cancer. Among these, choline (labeled with 18F or 11C), 11C-acetate, and 18F-fluoride have demonstrated promising results, and other new radiopharmaceuticals are currently under evaluation in preclinical and clinical studies. PMID:20425625
Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with (18)F positron emission tomography.
Scherer, Daniel J; Psaltis, Peter J
Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of (18)Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of (18)Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) and sodium (18)F-fluoride ((18)F-NaF). PMID:27500093
No-carrier-added (NCA) aryl [{sup 18}F]fluorides via the nucleophilic aromatic substitution of electron rich aromatic rings
Ding, Yu-Shin; Fowler, J.S.; Wolf, A.P.
A method for synthesizing no-carrier-added (NCA) aryl [{sup 18}F] fluoride substituted aromatic aldehyde compositions bearing an electron donating group is described. The method includes the step of reacting aromatic nitro aldehydes having a suitably protected hydroxyl substituent on an electron rich ring. The reaction is carried out by nucleophilic aromatic substitution with a no-carrier-added (NCA) [{sup 18}F]fluoride ion. The method can be used to synthesize various no-carrier-added aryl [{sup 18}F]fluoride compositions, including 6-[{sup 18}F]fluoro-L-DOPA, 2-[{sup 18}F]fluorotyrosine, 6-[{sup 18}F]fluoronorepinephrine, and 6-[{sup 18}F]fluorodopamine. In those instances when a racemic mixture of enantiomers is produced by the present invention, such as in the synthesis of 6-[{sup 18}F]fluoronorepinephrine, a preferred method also includes resolution of the racemic mixture on a chiral HPLC column. This procedure results in a high yield of enantiomerically pure [{sup 18}F] labeled isomers, for example [-]-6-[{sup 18}F]fluoronorepinephrine and [+]-6-[{sup 18}F]fluoronorepinephrine.
Reusable electrochemical cell for rapid separation of [18F]fluoride from [18O]water for flow-through synthesis of 18F-labeled tracers
Sadeghi, Saman; Liang, Vincent; Cheung, Shilin; Woo, Suh; Wu, Curtis; Ly, Jimmy; Deng, Yuliang; Eddings, Mark; van Dam, R. Michael
A brass-platinum electrochemical micro flow cell was developed to extract [18F]fluoride from an aqueous solution and release it into an organic based solution, suitable for subsequent radio-synthesis, in a fast and reliable manner. This cell does not suffer electrode erosion and is thus reusable while operating faster by enabling increased voltages. By optimizing temperature, trapping and release potentials, flow rates, and electrode materials, an overall [18F]fluoride trapping and release efficiency of 84±5% (n=7) was achieved. X-ray photoelectron spectroscopy (XPS) was used to analyze electrode surfaces of various metal-metal systems and the findings were correlated with the performance of the electrochemical cell. To demonstrate the reactivity of the released [18F]fluoride, the cell was coupled to a flow-through reactor and automated synthesis of [18F]FDG with a repeatable decay-corrected yield of 56±4% (n=4) was completed in <15 min. A multi-human dose of 5.92 GBq [18F]FDG was also demonstrated. PMID:23474380
Positron emission particle tracking using the new Birmingham positron camera
NASA Astrophysics Data System (ADS)
Parker, D. J.; Forster, R. N.; Fowles, P.; Takhar, P. S.
Since 1985 a positron camera consisting of a pair of multi-wire proportional chambers has been used at Birmingham for engineering studies involving positron emitting radioactive tracers. The technique of positron emission particle tracking (PEPT), developed at Birmingham, whereby a single tracer particle can be tracked at high speed, has proved particularly powerful. The main limitation of the original positron camera was its low sensitivity and correspondingly low data rate. A new positron camera has recently been installed; it consists of a pair of NaI (Tl) gamma camera heads with fully digital readout and offers an enormous improvement in data rate and data quality. The performance of this camera, and in particular the improved capabilities it brings to the PEPT technique, are summarised.
Positron Emission Mammotomography with Dual Planar Detectors
Mark Smith; Raymond Raylman; Stanislaw Majewski
Positron emission mammography (PEM) is usually performed with two stationary planar detectors above and below a compressed breast. There is image blurring normal to the detectors due to the limited angular range of the lines of response. Positron emission mammotomography (PEM-T) with dual planar detectors rotating about the breast can obtain complete angular sampling and has the potential to improve activity estimation.
Positron emission tomography wrist detector
Schlyer, David J.; O'Connor, Paul; Woody, Craig; Junnarkar, Sachin Shrirang; Radeka, Veljko; Vaska, Paul; Pratte, Jean-Francois
A method of serially transferring annihilation information in a compact positron emission tomography (PET) scanner includes generating a time signal representing a time-of-occurrence of an annihilation event, generating an address signal representing a channel detecting the annihilation event, and generating a channel signal including the time and address signals. The method also includes generating a composite signal including the channel signal and another similarly generated channel signal concerning another annihilation event. An apparatus that serially transfers annihilation information includes a time signal generator, address signal generator, channel signal generator, and composite signal generator. The time signal is asynchronous and the address signal is synchronous to a clock signal. A PET scanner includes a scintillation array, detection array, front-end array, and a serial encoder. The serial encoders include the time signal generator, address signal generator, channel signal generator, and composite signal generator.
Positron emission particle tracking using a modular positron camera
NASA Astrophysics Data System (ADS)
Parker, D. J.; Leadbeater, T. W.; Fan, X.; Hausard, M. N.; Ingram, A.; Yang, Z.
The technique of positron emission particle tracking (PEPT), developed at Birmingham in the early 1990s, enables a radioactively labelled tracer particle to be accurately tracked as it moves between the detectors of a "positron camera". In 1999 the original Birmingham positron camera, which consisted of a pair of MWPCs, was replaced by a system comprising two NaI(Tl) gamma camera heads operating in coincidence. This system has been successfully used for PEPT studies of a wide range of granular and fluid flow processes. More recently a modular positron camera has been developed using a number of the bismuth germanate (BGO) block detectors from standard PET scanners (CTI ECAT 930 and 950 series). This camera has flexible geometry, is transportable, and is capable of delivering high data rates. This paper presents simple models of its performance, and initial experience of its use in a range of geometries and applications.
Scintillators for positron emission tomography
Moses, W.W.; Derenzo, S.E.
Like most applications that utilize scintillators for gamma detection, Positron Emission Tomography (PET) desires materials with high light output, short decay time, and excellent stopping power that are also inexpensive, mechanically rugged, and chemically inert. Realizing that this ``ultimate`` scintillator may not exist, this paper evaluates the relative importance of these qualities and describes their impact on the imaging performance of PET. The most important PET scintillator quality is the ability to absorb 511 keV photons in a small volume, which affects the spatial resolution of the camera. The dominant factor is a short attenuation length ({le} 1.5 cm is required), although a high photoelectric fraction is also important (> 30% is desired). The next most important quality is a short decay time, which affects both the dead time and the coincidence timing resolution. Detection rates for single 511 keV photons can be extremely high, so decay times {le} 500 ns are essential to avoid dead time losses. In addition, positron annihilations are identified by time coincidence so {le}5 ns fwhm coincidence pair timing resolution is required to identify events with narrow coincidence windows, reducing contamination due to accidental coincidences. Current trends in PET cameras are toward septaless, ``fully-3D`` cameras, which have significantly higher count rates than conventional 2-D cameras and so place higher demands on scintillator decay time. Light output affects energy resolution, and thus the ability of the camera to identify and reject events where the initial 511 keV photon has undergone Compton scatter in the patient. The scatter to true event fraction is much higher in fully-3D cameras than in 2-D cameras, so future PET cameras would benefit from scintillators with a 511 keV energy resolution < 10--12% fwhm.
Addiction Studies with Positron Emission Tomography
Joanna Fowler
Brookhaven scientist Joanna Fowler describes Positron Emission Technology (PET) research at BNL which for the past 30 years has focused in the integration of basic research in radiotracer chemistry with the tools of neuroscience to develop new scientific
Addiction Studies with Positron Emission Tomography
Joanna Fowler
Brookhaven scientist Joanna Fowler describes Positron Emission Technology (PET) research at BNL which for the past 30 years has focused in the integration of basic research in radiotracer chemistry with the tools of neuroscience to develop new scientific
Stereoselective synthesis and biological evaluation of syn-1-amino-3-[18F]fluorocyclobutyl-1-carboxylic acid as a potential positron emission tomography brain tumor imaging agent.
Yu, Weiping; Williams, Larry; Camp, Vernon M; Malveaux, Eugene; Olson, Jeffrey J; Goodman, Mark M
Amino acid syn-1-amino-3-fluoro-cyclobutyl-1-carboxylic acid (syn-FACBC) 12, the isomer of anti-FACBC, has been selectively synthesized and [(18)F] radiofluorinated in 52% decay-corrected yield using no-carrier-added [(18)F]fluoride. The key step in the synthesis of the desired isomer involved stereoselective reduction using lithium alkylborohydride/zinc chloride, which improved the ratio of anti-alcohol to syn-alcohol from 17:83 to 97:3. syn-FACBC 12 entered rat 9L gliosarcoma cells primarily via L-type amino acid transport in vitro with high uptake of 16% injected dose per 5 x 10(5) cells. Biodistribution studies in rats with 9L gliosarcoma brain tumors demonstrated high tumor to brain ratio of 12:1 at 30 min post injection. In this model, amino acid syn-[(18)F]FACBC 12 is a promising metabolically based radiotracer for positron emission tomography brain tumor imaging.
Radiosynthesis and evaluation of an 18F-labeled positron emission tomography (PET) radioligand for brain histamine subtype-3 receptors based on a nonimidazole 2-aminoethylbenzofuran chemotype
Bao, Xiaofeng; Lu, Shuiyu; Liow, Jeih-San; Zoghbi, Sami S.; Jenko, Kimberly J.; Clark, David T.; Gladding, Robert L.; Innis, Robert B.; Pike, Victor W.
A known chemotype of H3 receptor ligand was explored for development of a radioligand for imaging brain histamine subtype 3 (H3) receptors in vivo with positron emission tomography (PET), namely non-imidazole 2-aminoethylbenzofurans, represented by the compound (R)-(2-(2-(2-methylpyrrolidin-1-yl)ethyl)benzofuran-5-yl)(4-fluorophenyl)methanone (9). Compound 9 was labeled with fluorine-18 (t1/2= 109.7 min) in high specific activity by treating the prepared nitro analog (12) with cyclotron-produced [18F]fluoride ion. [18F]9 was studied with PET in mouse and in monkey after intravenous injection. [18F]9 showed favorable properties as a candidate PET radioligand, including moderately high brain uptake with a high proportion of H3 receptor-specific signal in the absence of radiodefluorination. The nitro compound 12 was found to have even higher H3 receptor affinity, indicating the potential of this chemotype for the development of further promising PET radioligands. PMID:22313227
A Practical One-Pot Synthesis of Positron Emission Tomography (PET) Tracers via Nickel-Mediated Radiofluorination
Zlatopolskiy, Boris D; Zischler, Johannes; Urusova, Elizaveta A; Endepols, Heike; Kordys, Elena; Frauendorf, Holm; Mottaghy, Felix M; Neumaier, Bernd
Recently a novel method for the preparation of 18F-labeled arenes via oxidative [18F]fluorination of easily accessible and sufficiently stable nickel complexes with [18F]fluoride under exceptionally mild reaction conditions was published. The suitability of this procedure for the routine preparation of clinically relevant positron emission tomography (PET) tracers, 6-[18F]fluorodopamine (6-[18F]FDA), 6-[18F]fluoro-l-DOPA (6-[18F]FDOPA) and 6-[18F]fluoro-m-tyrosine (6-[18F]FMT), was evaluated. The originally published base-free method was inoperative. However, a "low base" protocol afforded protected radiolabeled intermediates in radiochemical conversions (RCCs) of 5–18 %. The subsequent deprotection step proceeded almost quantitatively (>95 %). The simple one-pot two-step procedure allowed the preparation of clinical doses of 6-[18F]FDA and 6-[18F]FDOPA within 50 min (12 and 7 % radiochemical yield, respectively). In an unilateral rat model of Parkinsons disease, 6-[18F]FDOPA with high specific activity (175 GBq μmol−1) prepared using the described nickel-mediated radiofluorination was compared to 6-[18F]FDOPA with low specific activity (30 MBq μmol−1) produced via conventional electrophilic radiofluorination. Unexpectedly both tracer variants displayed very similar in vivo properties with respect to signal-to-noise ratio and brain distribution, and consequently, the quality of the obtained PET images was almost identical. PMID:26478840
Lewis acid-assisted isotopic 18F-19F exchange in BODIPY dyes: facile generation of positron emission tomography/fluorescence dual modality agents for tumor imaging.
Liu, Shuanglong; Lin, Tzu-Pin; Li, Dan; Leamer, Lauren; Shan, Hong; Li, Zibo; Gabbaï, François P; Conti, Peter S
Positron emission tomography (PET) is a powerful technique for imaging biological pathways in vivo, particularly those that are key targets in disease processes. In contrast, fluorescence imaging has demonstrated to be a superior method for image-guided surgery, such as tumor removal. Although the integration of PET and optical imaging could provide an attractive strategy for patient management, there is a significant shortage of established platforms/methods for PET/optical probe construction. In this study, various reaction conditions were explored to develop a simple and fast method allowing for the introduction of [(18)F]-fluoride into BODIPY dyes. Through a systematic optimization of the reaction conditions, we found that BODIPY dyes, including commercial amine-reactive BODIPY succinimidyl esters, may be converted into their radioactive analogues in the matter of minutes via a (18)F-(19)F isotopic exchange reaction promoted by a Lewis acid such as SnCl4. An integrin-targeting RGD peptide was also conjugated with [(18)F]BODIPY® R6G , derived from the commercially available BODIPY® R6G fluorescent tag, to provide a [(18)F]-RGD conjugate in 82% yield. In vivo evaluation of this imaging probe showed a discernible tumor uptake in the U87MG xenograft model. The dual modality imaging properties of the probe was confirmed by ex vivo fluorescence and microPET imaging experiments. In summary, in the matter of minutes, BODIPY dyes were converted into their "hot" radioactive analogues via a (18)F-(19)F isotopic exchange reaction promoted by a Lewis acid. This approach, which can be applied to commercial BODIPY dyes, provides easy access to positron emission tomography/fluorescence dual modality imaging agents. PMID:23471211
Advanced Instrumentation for Positron Emission Tomography [PET
DOE R&D Accomplishments Database
Derenzo, S. E.; Budinger, T. F.
This paper summarizes the physical processes and medical science goals that underlay modern instrumentation design for Positron Emission Tomography. The paper discusses design factors such as detector material, crystalphototube coupling, shielding geometry, sampling motion, electronics design, time-of-flight, and the interrelationships with quantitative accuracy, spatial resolution, temporal resolution, maximum data rates, and cost.
Positron emission tomography - a new approach to brain chemistry
Jacobson, H.G.
Positron emission tomography permits examination of the chemistry of the brain in living beings. Until recently, positron emission tomography had been considered a research tool, but it is rapidly moving into clinical practice. This report describes the uses and applications of positron emission tomography in examinations of patients with strokes, epilepsy, malignancies, dementias, and schizophrenia and in basic studies of synaptic neurotransmission.
Positron emission tomography: An overview
Shukla, A. K.; Kumar, Utham
The rate of glucose utilization in tumor cells is significantly enhanced as compared to normal cells and this biochemical characteristic is utilized in PET imaging using FDG as a major workhorse. The PET systems as well as cyclotrons producing positron emitting radiopharmaceuticals have undergone continuous technological refinements. While PET (CT) systems enable fusion images as well as precise attenuation correction, the self-shielded cyclotrons developed provide dedicated systems for in-house production of a large number of PET radiopharmaceuticals. The application of PET images in oncology includes those of pulmonary, colorectal, breast, lymphoma, head & neck, bone, ovarian and GI cancers. The PET has been recognized as promising diagnostic tool to predict biological and physiological changes at the molecular level and hence offer a potential area for future applications including Stem Cell research. PMID:21206635
N-(3-( sup 18 F)fluoropropyl)-N-nordiprenorphine: Synthesis and characterization of a new agent for imaging opioid receptors with positron emission tomography
Chesis, P.L.; Hwang, D.R.; Welch, M.J. )
A series of N-fluoroalkyl (1-5) and N-alkyl (6-8) analogues of the high-affinity opioid receptor antagonist diprenorphine (9) has been synthesized and evaluated with in vitro binding assays. Three of the N-fluoroalkyl compounds were prepared with the positron-emitting radionuclide {sup 18}F (1a, 2a, 5a), and their biodistribution was determined in rats. Compounds 2a and 5a were made by using a two-step labeling procedure, ({sup 18}F)fluoride displacement of an iodoalkyl triflate followed by N-alkylation, that required 2 h and proceeded in 4-6% overall radiochemical yield at the end of synthesis. The effective specific activity of compounds 2a and 5a, determined by competitive receptor binding assay, was 840-1820 Ci/mmol. Compound 1a was made by the same two-step procedure, with the bromoalkyl triflate, in 0.3-0.6% radiochemical yield at an effective specific activity of 106-264 Ci/mmol. Specificity of binding in vivo was measured as the percent injected dose/gram of striatal tissue divided by the percent injected dose/gram of cerebellar tissue. The best striatum to cerebellum ratio (3.32 +/- 0.74 at 30 min) was achieved with N-(3-({sup 18}F)-fluoropropyl)-N-nordiprenorphine (2a, ({sup 18}F)FPND). The high specific binding demonstrated by this compound indicates that it may be useful for in vivo imaging of opioid receptors with positron emission tomography.
Comparisons between glucose analogue 2-deoxy-2-(18F)fluoro-D-glucose and 18F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions
Capitanio, Selene; Bongioanni, Francesca; Piccardo, Arnoldo; Campus, Claudio; Gonella, Roberta; Tixi, Lucia; Naseri, Mehrdad; Pennone, Michele; Altrinetti, Vania; Buschiazzo, Ambra; Bossert, Irene; Fiz, Francesco; Bruno, Andrea; DeCensi, Andrea; Sambuceti, Gianmario; Morbelli, Silvia
AIM: To compare 2-deoxy-2-(18F)fluoro-D-glucose(18F-FDG) and 18F-sodium (18F-NaF) positron emission tomography/computed tomography (PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases. METHODS: A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent 18F-FDG and 18F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity (Se), specificity (Sp), overall accuracy, positive and negative predictive values, error rate, and Youden's index. McNemar's χ2 test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the co-registered CT (sclerotic, lytic, mixed, no-lesions) and the divergent site of disease (skull, spine, ribs, extremities, pelvis). The impact of adding 18F-NaF PET/CT to the work-up of patients was also measured in terms of change in their management due to 18F-NaF PET/CT findings. RESULTS: The two imaging methods of 18F-FDG and 18F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively (McNemar's χ2 = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis (McNemar's χ2 = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, 18F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis (P < 0.002) and vertebral localizations (P < 0.002); 18F-NaF PET/CT was more accurate in detecting sclerotic (P < 0.005) and rib lesions (P < 0.04). 18F-NaF PET/CT led to a
Positron Emission Tomography: Its 65 years
NASA Astrophysics Data System (ADS)
Del Guerra, A.; Belcari, N.; Bisogni, M.
Positron Emission Tomography (PET) is a well-established imaging technique for in vivo molecular imaging. In this review after a brief history of PET there are presented its physical principles and the technology that has been developed for bringing PET from a bench experiment to a clinical indispensable instrument. The limitations and performance of the PET tomographs are discussed, both as for the hardware and software aspects. The status of art of clinical, pre-clinical and hybrid scanners (, PET/CT and PET/MR) is reported. Finally the actual trend and the recent and future technological developments are fully illustrated.
Level Set Method for Positron Emission Tomography
Chan, Tony F.; Li, Hongwei; Lysaker, Marius; Tai, Xue-Cheng
In positron emission tomography (PET), a radioactive compound is injected into the body to promote a tissue-dependent emission rate. Expectation maximization (EM) reconstruction algorithms are iterative techniques which estimate the concentration coefficients that provide the best fitted solution, for example, a maximum likelihood estimate. In this paper, we combine the EM algorithm with a level set approach. The level set method is used to capture the coarse scale information and the discontinuities of the concentration coefficients. An intrinsic advantage of the level set formulation is that anatomical information can be efficiently incorporated and used in an easy and natural way. We utilize a multiple level set formulation to represent the geometry of the objects in the scene. The proposed algorithm can be applied to any PET configuration, without major modifications. PMID:18354724
Positron emission tomography tracers for imaging angiogenesis
Beer, Ambros J.; Wang, Hui; Chen, Xiaoyuan
Position emission tomography imaging of angiogenesis may provide non-invasive insights into the corresponding molecular processes and may be applied for individualized treatment planning of antiangiogenic therapies. At the moment, most strategies are focusing on the development of radiolabelled proteins and antibody formats targeting VEGF and its receptor or the ED-B domain of a fibronectin isoform as well as radiolabelled matrix metalloproteinase inhibitors or αvβ3 integrin antagonists. Great efforts are being made to develop suitable tracers for different target structures. All of the major strategies focusing on the development of radiolabelled compounds for use with positron emission tomography are summarized in this review. However, because the most intensive work is concentrated on the development of radiolabelled RGD peptides for imaging αvβ3 expression, which has successfully made its way from bench to bedside, these developments are especially emphasized. PMID:20559632
Positron Emission Tomography: A Basic Analysis
NASA Astrophysics Data System (ADS)
Kerbacher, M. E.; Deaton, J. W.; Phinney, L. C.; Mitchell, L. J.; Duggan, J. L.
Positron Emission Tomography is useful in detecting biological abnormalities. The technique involves attaching radiotracers to a material used inside the body, in many cases glucose. Glucose is absorbed most readily in areas of unusual cell growth or uptake of nutrients so through natural processes the treated glucose highlights regions of tumors and other degenerative disorders such as Alzheimer's disease. The higher the concentration of isotopes, the more dynamic the area. Isotopes commonly used as tracers are 11C, 18F, 13N, and 15O due to their easy production and short half-lives. Once the tracers have saturated an area of tissue they are detected using coincidence detectors collinear with individual isotopes. As the isotope decays it emits a positron which, upon annihilating an electron, produces two oppositely directioned gamma rays. The PET machine consists of several pairs of detectors, each 180 degrees from their partner detector. When the oppositely positioned detectors are collinear with the area of the isotope, a computer registers the location of the isotope and can compile an image of the activity of the highlighted area based on the position and strength of the isotopes.
Compact conscious animal positron emission tomography scanner
Schyler, David J.; O'Connor, Paul; Woody, Craig; Junnarkar, Sachin Shrirang; Radeka, Veljko; Vaska, Paul; Pratte, Jean-Francois; Volkow, Nora
A method of serially transferring annihilation information in a compact positron emission tomography (PET) scanner includes generating a time signal for an event, generating an address signal representing a detecting channel, generating a detector channel signal including the time and address signals, and generating a composite signal including the channel signal and similarly generated signals. The composite signal includes events from detectors in a block and is serially output. An apparatus that serially transfers annihilation information from a block includes time signal generators for detectors in a block and an address and channel signal generator. The PET scanner includes a ring tomograph that mounts onto a portion of an animal, which includes opposing block pairs. Each of the blocks in a block pair includes a scintillator layer, detection array, front-end array, and a serial encoder. The serial encoder includes time signal generators and an address signal and channel signal generator.
Positron Emission Tomography with improved spatial resolution
Drukier, A.K.
Applied Research Corporation (ARC) proposed the development of a new class of solid state detectors called Superconducting Granular Detectors (SGD). These new detectors permit considerable improvements in medical imaging, e.g. Positron Emission Tomography (PET). The biggest impact of this technique will be in imaging of the brain. It should permit better clinical diagnosis of such important diseases as Altzheimer's or schizophrenia. More specifically, we will develop an improved PET-imager; a spatial resolution 2 mm may be achievable with SGD. A time-of-flight capability(t {approx} 100 psec) will permit better contrast and facilitate 3D imaging. In the following, we describe the results of the first 9 months of the development.
Positron Emission Tomography of the Heart
DOE R&D Accomplishments Database
Schelbert, H. R.; Phelps, M. E.; Kuhl, D. E.
Positron emission computed tomography (PCT) represents an important new tool for the noninvasive evaluation and, more importantly, quantification of myocardial performance. Most currently available techniques permit assessment of only one aspect of cardiac function, i.e., myocardial perfusion by gamma scintillation camera imaging with Thallium-201 or left ventricular function by echocardiography or radionuclide angiocardiography. With PCT it may become possible to study all three major segments of myocardial performance, i.e., regional blood flow, mechanical function and, most importantly, myocardial metabolism. Each of these segments can either be evaluated separately or in combination. This report briefly describes the principles and technological advantages of the imaging device, reviews currently available radioactive tracers and how they can be employed for the assessment of flow, function and metabolism; and, lastly, discusses possible applications of PCT for the study of cardiac physiology or its potential role in the diagnosis of cardiac disease.
Imaging Tumor Metabolism Using Positron Emission Tomography
Lewis, David Y.; Soloviev, Dmitry; Brindle, Kevin M.
Positron emission tomography (PET) is an extraordinarily sensitive clinical imaging modality for interrogating tumor metabolism. Radiolabelled PET substrates can be traced at sub-physiological concentrations, allowing non-invasive imaging of metabolism and intra-tumoral heterogeneity in systems ranging from advanced cancer models to cancer patients in the clinic. There are a wide range of novel and more established PET radiotracers, which can be used to investigate various aspects of tumor metabolism, including carbohydrate, amino acid and fatty acid metabolism. In this review we will briefly discuss the more established metabolic tracers and describe recent work on the development of new tracers. Some of the unanswered questions in tumor metabolism will be considered alongside new technical developments, such as combined PET/MRI machines, that could provide new imaging solutions to some of the outstanding diagnostic challenges facing modern cancer medicine. PMID:25815854
Improved photomultiplier tube for positron emission tomography.
Woldeselassie, T
The paper describes an investigation in which it is shown that small positive voltage pulses applied to an external conductor placed against the photocathode of a photomultiplier tube can be used to switch the photocathode completely off for the duration of the pulses. This suggests that a photomultiplier tube with a multisegment photocathode can be constructed, the individual cathode segments of which can be switched off independently by means of such pulses. A theoretical explanation for the effect is provided with the aid of a simple circuit model for the photocathode. Analysis of the model also shows that it is possible to identify the particular cathode segment in which a photon is detected when a pulse is recorded at the phototube's anode. A phototube with these characteristics can have important implications for positron emission tomography, as it can provide improved spatial resolution, simultaneous multislice capability and the ability to eliminate distortion due to dead-time effects at high count rates.
Positron emission tomography features of hidradenitis suppurativa
Simpson, R C; Dyer, M J S; Entwisle, J; Harman, K E
A 35-year-old male with classical Hodgkin's lymphoma (nodular sclerosing, grade 1 histology, clinical stage 2A) underwent a positron emission tomography (PET) scan to assess response to treatment. Half body CT PET imaging was obtained using a Siemens Biograph scanner from eyes to thighs. 405 MBq of 18-fluorodeoxyglucose (FDG) was injected with acquisition starting at 60 min. There was unexpected intense focal uptake in the superficial subcutaneous tissues of the abdomen, pelvis and lateral chest wall with overlying skin thickening seen on the CT component. This was initially of concern, but the patient was known to have a history of hidradenitis suppurativa (HS). On further examination, the radiological abnormalities corresponded to the clinical sites of involvement. To the best of our knowledge, this is the first documentation of the appearance of HS on PET scan. PMID:21750134
Positron emission tomography and radiation oncology
NASA Astrophysics Data System (ADS)
Fullerton, PhD, Gary D.; Fox, MD, Peter; Phillips, MD, William T.
Medical physics research is providing new avenues for addressing the fundamental problem of radiation therapy-how to provide a tumor-killing dose while reducing the dose to a non-lethal level for critical organs in adjacent portions of the patient anatomy. This talk reviews the revolutionary impact of Positron Emission Tomography on the practice of radiation oncology. The concepts of PET imaging and the development of "tumor" imaging methods using 18F-DG flouro-deoxyglucose are presented to provide the foundation for contemporary research and application to therapy. PET imaging influences radiation therapy decisions in multiple ways. Imaging of occult but viable tumor metastases eliminates misguided therapy attempts. The ability to distinguish viable tumor from scar tissue and necroses allows reduction of treatment portals and more selective treatments. Much research remains before the clinical benefits of these advances are fully realized.
Instrumentation optimization for positron emission mammography
Moses, William W.; Qi, Jinyi
The past several years have seen designs for PET cameras optimized to image the breast, commonly known as Positron Emission Mammography or PEM cameras. The guiding principal behind PEM instrumentation is that a camera whose field of view is restricted to a single breast has higher performance and lower cost than a conventional PET camera. The most common geometry is a pair of parallel planes of detector modules, although geometries that encircle the breast have also been proposed. The ability of the detector modules to measure the depth of interaction (DOI) is also a relevant feature. This paper finds that while both the additional solid angle coverage afforded by encircling the breast and the decreased blurring afforded by the DOI measurement improve performance, the ability to measure DOI is more important than the ability to encircle the breast.
Recent Developments in Positron Emission Tomography (PET) Instrumentation
DOE R&D Accomplishments Database
Derenzo, S. E.; Budinger, T. F.
This paper presents recent detector developments and perspectives for positron emission tomography (PET) instrumentation used for medical research, as well as the physical processes in positron annihilation, photon scattering and detection, tomograph design considerations, and the potentials for new advances in detectors.
Positron Emission Tomography Imaging of Atherosclerosis
Orbay, Hakan; Hong, Hao; Zhang, Yin; Cai, Weibo
Atherosclerosis-related cardiovascular events are the leading causes of death in the industrialized world. Atherosclerosis develops insidiously and the initial manifestation is usually sudden cardiac death, stroke, or myocardial infarction. Molecular imaging is a valuable tool to identify the disease at an early stage before fatal manifestations occur. Among the various molecular imaging techniques, this review mainly focuses on positron emission tomography (PET) imaging of atherosclerosis. The targets and pathways that have been investigated to date for PET imaging of atherosclerosis include: glycolysis, cell membrane metabolism (phosphatidylcholine synthesis), integrin αvβ3, low density lipoprotein (LDL) receptors (LDLr), natriuretic peptide clearance receptors (NPCRs), fatty acid synthesis, vascular cell adhesion molecule-1 (VCAM-1), macrophages, platelets, etc. Many PET tracers have been investigated clinically for imaging of atherosclerosis. Early diagnosis of atherosclerotic lesions by PET imaging can help to prevent the premature death caused by atherosclerosis, and smooth translation of promising PET tracers into the clinic is critical to the benefit of patients. PMID:24312158
Data acquisition with a positron emission tomograph
Freifelder, R.; Karp, J.S.
Positron Emission Tomography (PET) is a clinical imaging modality used in Nuclear Medicine. PET measures functionality rather than anatomical features and is therefore invaluable in the treatment of diseases which are characterized by functional changes in organs rather than anatomical changes. Typical diseases for which PET is used are cancer, epilepsy, and heart disease. While the scanners are not very complex, the performance demands on the devices are high. Excellent spatial resolution, 4-5 mm, and high sensitivity are key to maintaining high image quality. Compensation or suppression of scattered radiation is also necessary for good image quality. The ability to acquire data under high counting rates is also necessary in order to minimize the injected dose to the patient, minimize the patient`s time in the scanner, and finally to minimize blurring due to patient motion. We have adapted various techniques in our data acquisition system which will be reported on in this talk. These include pulse clipping using lumped delay lines, flash ADCs with short sampling time, the use of a local positioning algorithm to limit the number of data words being used in subsequent second level software triggers and calculations, and finally the use of high speed dedicated calculator boards for on-line rebinning and reduction of the data. Modifications to the system to allow for transmission scanning will also be discussed.
Positron emission tomography in generalized seizures
Theodore, W.H.; Brooks, R.; Margolin, R.; Patronas, N.; Sato, S.; Porter, R.J.; Mansi, L.; Bairamian, D.; DiChiro, G.
The authors used /sup 18/F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to study nine patients with clinical absence or generalized seizures. One patient had only absence seizures, two had only generalized tonic-clonic seizures, and six had both seizure types. Interictal scans in eight failed to reveal focal or lateralized hypometabolism. No apparent abnormalities were noted. Two patients had PET scans after isotope injection during hyperventilation-induced generalized spike-wave discharges. Diffusely increased metabolic rates were found in one compared with an interictal scan, and in another compared with control values. Another patient had FDG injected during absence status: EEG showed generalized spike-wave discharges (during which she was unresponsive) intermixed with slow activity accompanied by confusion. Metabolic rates were decreased, compared with the interictal scan, throughout both cortical and subcortical structures. Interictal PET did not detect specific anatomic regions responsible for absence seizure onset in any patient, but the results of the ictal scans did suggest that pathophysiologic differences exist between absence status and single absence attacks.
Resistive plate chambers in positron emission tomography
NASA Astrophysics Data System (ADS)
Crespo, Paulo; Blanco, Alberto; Couceiro, Miguel; Ferreira, Nuno C.; Lopes, Luís; Martins, Paulo; Ferreira Marques, Rui; Fonte, Paulo
Resistive plate chambers (RPC) were originally deployed for high energy physics. Realizing how their properties match the needs of nuclear medicine, a LIP team proposed applying RPCs to both preclinical and clinical positron emission tomography (RPC-PET). We show a large-area RPC-PET simulated scanner covering an axial length of 2.4m —slightly superior to the height of the human body— allowing for whole-body, single-bed RPC-PET acquisitions. Simulations following NEMA (National Electrical Manufacturers Association, USA) protocols yield a system sensitivity at least one order of magnitude larger than present-day, commercial PET systems. Reconstruction of whole-body simulated data is feasible by using a dedicated, direct time-of-flight-based algorithm implemented onto an ordered subsets estimation maximization parallelized strategy. Whole-body RPC-PET patient images following the injection of only 2mCi of 18-fluorodesoxyglucose (FDG) are expected to be ready 7 minutes after the 6 minutes necessary for data acquisition. This compares to the 10-20mCi FDG presently injected for a PET scan, and to the uncomfortable 20-30minutes necessary for its data acquisition. In the preclinical field, two fully instrumented detector heads have been assembled aiming at a four-head-based, small-animal RPC-PET system. Images of a disk-shaped and a needle-like 22Na source show unprecedented sub-millimeter spatial resolution.
Positron emission tomography for the assessment of myocardial viability
Schelbert, H.R. )
The detection of viable myocardium or ischemically injured myocardium with a reversible impairment of contractile function remains clinically important but challenging. Detection of reversible dysfunction and distinction from irreversible tissue injury by positron emission tomography is based on identification of preserved or even enhanced glucose metabolism with F-18 2-fluoro 2-deoxyglucose. Regional patterns of myocardial glucose utilization and blood flow, defined as perfusion-metabolism mismatches or matches, on positron emission tomography in patients with chronic or even acute ischemic heart disease are highly accurate in predicting the functional outcome after interventional revascularization. Compared with thallium-201 redistribution scintigraphy, positron emission tomography appears to be diagnostically more accurate, especially in patients with severely impaired left ventricular function. While larger clinical trials are needed for further confirmation, positron emission tomography has already proved clinically useful for stratifying patients with poor left ventricular function to the most appropriate therapeutic approach.
The Role of Chemistry in Positron Emission Tomography.
ERIC Educational Resources Information Center
Feliu, Anthony L.
Investigates use of positron emission tomography (PET) to study in-vivo metabolic processes. Discusses methodology of PET and medical uses. Outlines the production of different radioisotopes used in PET radiotracers. Includes selected bibliography. (ML)
Positron emission tomography imaging of prostate cancer
Hong, Hao; Zhang, Yin; Sun, Jiangtao; Cai, Weibo
Prostate cancer (PCa) is the second leading cause of cancer death among men in the United States. Positron emission tomography (PET), a non-invasive, sensitive, and quantitative imaging technique, can facilitate personalized management of PCa patients. There are two critical needs for PET imaging of PCa, early detection of primary lesions and accurate imaging of PCa bone metastasis, the predominant cause of death in PCa. Since the most widely used PET tracer in the clinic, 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG), does not meet these needs, a wide variety of PET tracers have been developed for PCa imaging which span an enormous size range from small molecules to intact antibodies. In this review, we will first summarize small molecule-based PET tracers for PCa imaging, which measure certain biological events such as cell membrane metabolism, fatty acid synthesis, and receptor expression. Next, we will discuss radiolabeled amino acid derivatives (e.g. methionine, leucine, tryptophan, and cysteine analogs), which are primarily based on the increased amino acid transport of PCa cells. Peptide-based tracers for PET imaging of PCa, mostly based on the bombesin peptide and its derivatives which bind to the gastrin-releasing peptide receptor, will then be presented in detail. We will also cover radiolabeled antibodies and antibody fragments (e.g. diabodies and minibodies) for PET imaging of PCa, targeting integrin αvβ3, EphA2, the epidermal growth factor receptor, or the prostate stem cell antigen. Lastly, we will identify future directions for the development of novel PET tracers for PCa imaging, which may eventually lead to personalized management of PCa patients. PMID:19946787
Positron Emission Mammography with Multiple Angle Acquisition
Mark F. Smith; Stan Majewski; Raymond R. Raylman
Positron emission mammography (PEM) of F-18 fluorodeoxyglucose (FDG) uptake in breast tumors with dedicated detectors typically has been accomplished with two planar detectors in a fixed position with the breast under compression. The potential use of PEM imaging at two detector positions to guide stereotactic breast biopsy has motivated us to use PEM coincidence data acquired at two or more detector positions together in a single image reconstruction. Multiple angle PEM acquisition and iterative image reconstruction were investigated using point source and compressed breast phantom acquisitions with 5, 9, 12 and 15 mm diameter spheres and a simulated tumor:background activity concentration ratio of 6:1. Image reconstruction was performed with an iterative MLEM algorithm that used coincidence events between any two detector pixels on opposed detector heads at each detector position. This present study compared two acquisition protocols: 2 angle acquisition with detector angular positions of -15 and +15 degrees and 11 angle acquisition with detector positions spaced at 3 degree increments over the range -15 to +15 degrees. Three- dimensional image resolution was assessed for the point source acquisitions, and contrast and signal-to-noise metrics were evaluated for the compressed breast phantom with different simulated tumor sizes. Radial and tangential resolutions were similar for the two protocols, while normal resolution was better for the 2 angle acquisition. Analysis is complicated by the asymmetric point spread functions. Signal- to-noise vs. contrast tradeoffs were better for 11 angle acquisition for the smallest visible 9 mm sphere, while tradeoff results were mixed for the larger and more easily visible 12 mm and 15 mm diameter spheres. Additional study is needed to better understand the performance of limited angle tomography for PEM. PEM tomography experiments with complete angular sampling are planned.
Positron Emission Mammography with Multiple Angle Acquisition
Mark F. Smith; Stan Majewski; Raymond R. Raylman
Positron emission mammography (PEM) of F-18 fluorodeoxyglucose (FbG) uptake in breast tumors with dedicated detectors typically has been accomplished with two planar detectors in a fixed position with the breast under compression. The potential use of PEM imaging at two detector positions to guide stereotactic breast biopsy has motivated us to use PEM coincidence data acquired at two or more detector positions together in a single image reconstruction. Multiple angle PEM acquisition and iterative image reconstruction were investigated using point source and compressed breast phantom acquisitions with 5, 9, 12 and 15 mm diameter spheres and a simulated tumor:background activity concentration ratio of 6:1. Image reconstruction was performed with an iterative MLEM algorithm that used coincidence events between any two detector pixels on opposed detector heads at each detector position. This present study compared two acquisition protocols: 2 angle acquisition with detector angular positions of -15 and +15 degrees and 11 angle acquisition with detector positions spaced at 3 degree increments over the range -15 to +15 degrees. Three-dimensional image resolution was assessed for the point source acquisitions, and contrast and signal-to-noise metrics were evaluated for the compressed breast phantom with different simulated tumor sizes. Radial and tangential resolutions were similar for the two protocols, while normal resolution was better for the 2 angle acquisition. Analysis is complicated by the asymmetric point spread functions. Signal- to-noise vs. contrast tradeoffs were better for 11 angle acquisition for the smallest visible 9 mm sphere, while tradeoff results were mixed for the larger and more easily visible 12 mm and 15 mm diameter spheres. Additional study is needed to better understand the performance of limited angle tomography for PEM. PEM tomography experiments with complete angular sampling are planned.
Radiofluorinated carbohydrates for positron emission tomography.
Mun, Jiyoung
2-Deoxy-2-[(18)F]fluoro-D-glucose (2-(18)FDG) has represented radiofluorinated carbohydrates as the most successful tracer for positron emission tomography (PET). 2-(18)FDG uptake depends on glucose metabolism, which is related to a disease progression. 2-(18)FDG has been widely used in oncology, neurology, cardiology, infectious diseases, and inflammation, to complement anatomical modalities such as CT and MRI. Followed by the success of 2-(18)FDG, various radiofluorinated carbohydrates have been evaluated as PET tracers, which include analogs of D-ribose, D-mannose, D-galactose, D-talose, D-fructose, D-allose, lactose, L-fucose, N-acetylneuraminic acid, and L-ascorbic acid. Among those radiofluorinated carbohydrates, several have implied potential for further development. 2-Deoxy-2-[(18)F]fluoro-D-galactose has been developed to assess liver function and diagnose hepatic carcinoma. 6-Deoxy-6-[(18)F]fluoro-D-fructose showed promising characteristics for diagnosis of breast cancer. Three radiofluorinated analogs of lactose have been designed as the substrates of the overexpressed hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein in peritumoral pancreatic tissue for early diagnosis of pancreatic cancer. The metabolism of 6-[(18)F]fluoro-L-fucose suggested that it is a bioactive analog of L-fucose in the synthesis of glycoconjugate macromolecules. 6-Deoxy-6-[(18)F]fluoro-L-ascorbic acid was evaluated to assess antioxidant function of L-ascorbic acid in rodent models of transient global ischemia and glutathione deficiency.
Radiodefluorination of 3-Fluoro-5-(2-(2-[18F](fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile ([18F]SP203), a Radioligand for Imaging Brain Metabotropic Glutamate Subtype-5 Receptors with Positron Emission Tomography, Occurs by Glutathionylation in Rat Brain
Zoghbi, Sami S.; Siméon, Fabrice G.; Liow, Jeih-San; Brown, Amira K.; Kannan, Pavitra; Innis, Robert B.; Pike, Victor W.
Metabotropic glutamate subtype-5-receptors (mGluR5) are implicated in several neuropsychiatric disorders. Positron emission tomography (PET) with a suitable radioligand may enable monitoring of regional brain mGluR5 density before and during treatments. We have developed a new radioligand, 3-fluoro-5-(2-(2-[18F](fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile ([18F]SP203), for imaging brain mGluR5 in monkey and human. In monkey, radioactivity was observed in bone, showing release of [18F]fluoride ion from [18F]SP203. This defluorination was not inhibited by disulfiram, a potent inhibitor of CYP2E1. PET confirmed bone uptake of radioactivity and therefore defluorination of [18F]SP203 in rats. To understand the biochemical basis for defluorination, we administered [18F]SP203 plus SP203 in rats for ex vivo analysis of metabolites. Radio-HPLC detected [18F]fluoride ion as a major radiometabolite in both brain extract and urine. Incubation of [18F]SP203 with brain homogenate also generated this radiometabolite, whereas no metabolism was detected in whole blood in vitro. LC-MS analysis of the brain extract detected m/z 548 and m/z 404 ions, assignable to the [M+H]+ of S-glutathione (SP203Glu) and N-acetyl-S-L-cysteine (SP203Nac) conjugates of SP203, respectively. In urine, only the [M+H]+ of SP203Nac was detected. MS-MS and MS3 analyses of each metabolite yielded product ions consistent with its proposed structure, including the former fluoromethyl group as the site of conjugation. Metabolite structures were confirmed by similar analyses of SP203Glu and SP203Nac, prepared by glutathione S-transferase reaction and chemical synthesis, respectively. Thus, glutathionylation at the 2-fluoromethyl group is responsible for the radiodefluorination of [18F]SP203 in rat. This study provides the first demonstration of glutathione-promoted radiodefluorination of a PET radioligand. PMID:18806125
Application of mathematical removal of positron range blurring in Positron Emission Tomography
Haber, S.F.; Derenzo, S.E.; Uber, D.
The range of positrons in tissue is an important limitation to the ultimate spatial resolution achievable in Positron Emission Tomography. In this work we applied a Fourier deconvolution technique to remove range blurring in images taken by the Donner 600-Crystal Positron Tomograph. Using phantom data, we found significant improvement in the image quality and the FWHM for both {sup 68}Ga and {sup 82}Rb. These were successfully corrected so that the images and FWHM almost matched those of {sup 18}F which has negligible positron range. However, statistical noise was increased by the deconvolution process and it was not practical to recover the full spatial resolution of the tomograph. 10 refs., 6 figs., 3 tabs.
Application of mathematical removal of positron range blurring in positron emission tomography
Haber, S.F.; Derenzo, S.E.; Uber, D. )
The range of positrons in tissue is an important limitation to the ultimate spatial resolution achievable in positron emission tomography. In this work the authors have applied a Fourier deconvolution technique to remove range blurring in images taken by the Donner 600-crystal positron tomograph. Using phantom data, the authors have found significant improvement in the image quality and the FWHM for both {sup 68}Ga and {sup 82}Rb. These were successfully corrected so that the images and FWHM almost matched those of {sup 18}F which has negligible positron range. However, statistical noise was increased by the deconvolution process and it was not practical to recover the full spatial resolution of the tomograph.
Positron emission tomographic imaging of tumors using monoclonal antibodies
Zalutsky, M.R.
This research project is developing methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). This report describes the development of methods for labeling MAbs and their fragments with positron-emitting halogen nuclides, fluorine-18 and iodine-124. These nulides were selected because of the widespread availability of F-18 and because of our extensive experience in the development of new protein radiohalogenation methods.
[Assessing myocardial perfusion with positron emission tomography].
vom Dahl, J
Positron emission tomography (PET) of the heart has gained widespread scientific and clinical acceptance with regard to two indications: 1) The detection of perfusion abnormalities by qualitative and semiquantitative analyses of perfusion images at rest and during physical or pharmacological stress using well-validated perfusion tracers, such as N-13 ammonia, Rb-82 rubidium chloride, or O-15 labeled water. 2) Viability imaging of myocardial regions with reduced contractility by combining perfusion measurements with substrate metabolism as assessed from F-18 deoxyglucose utilization. This overview summarizes the use of PET as a perfusion imaging method. With a sensitivity > 90% in combination with high specificity, PET is today the best-validated available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. The high diagnostic accuracy and the methological advantages as compared to conventional scintigraphy allows one to use PET perfusion imaging to detect subtle changes in the perfusion reserve for the detection of CAD in high risk but asymptomatic patients as well as in patients with proven CAD undergoing various treatment forms such as risk factor reduction or coronary revascularization. In patients following orthotopic heart transplantation, evolving transplant vasculopathy can be detected at an early stage. Quantitative PET imaging at rest allows for detection of myocardial viability since cellular survival is based on maintenance of a minimal perfusion and structural changes correlate to the degree of perfusion reduction. Furthermore, quantitative assessment of the myocardial perfusion reserve detects the magnitude and competence of collaterals in regions with occluded epicardial collaterals and, thus, imaging of several coronary distribution territories in one noninvasive
Positron emission tomographic imaging of cardiac sympathetic innervation and function
Goldstein, D.S.; Chang, P.C.; Eisenhofer, G.; Miletich, R.; Finn, R.; Bacher, J.; Kirk, K.L.; Bacharach, S.; Kopin, I.J. )
Sites of uptake, storage, and metabolism of ({sup 18}F)fluorodopamine and excretion of ({sup 18}F)fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of ({sup 18}F)-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of ({sup 18}F)fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function.
Clinical oncologic positron emission tomography: an introduction.
Turkington, Timothy G; Coleman, R Edward
PET imaging is a molecular imaging technology that is diffusing into imaging departments quite rapidly. The unique characteristics of positron emitting radionuclides such as fluorine-18 provide high-quality images with reasonable acquisition times. The imaging instrumentation continues to improve with new detector materials and combinations of PET scanners and CT scanners. FDG is now readily available to most hospitals in the United States. Third-party payers now recognize the importance of PET imaging in multiple malignancies. The number of PET scans performed annually will continue to increase as the indications increase and the instrumentation is more available.
Positron Emission Tomography: Human Brain Function and Biochemistry.
ERIC Educational Resources Information Center
Phelps, Michael E.; Mazziotta, John C.
Describes the method, present status, and application of positron emission tomography (PET), an analytical imaging technique for "in vivo" measurements of the anatomical distribution and rates of specific biochemical reactions. Measurements and image dynamic biochemistry link basic and clinical neurosciences with clinical findings suggesting…
Positron emission tomographic imaging of tumors using monoclonal antibodies
Zalutsky, M.R. . Dept. of Radiology)
The overall objective of this research project is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Both diagnostic and therapeutic applications of labeled MAbs could be improved as a result of knowledge obtained through the exploitation of the advantageous imaging characteristics associated with PET. By labeling MAbs with positron-emitting nuclides, it should be possible to quantitate the dynamics of their three-dimensional distribution in vivo. Our long-term goals are to apply this approach. 3 tabs.
Positron emission zone plate holography for particle tracking
NASA Astrophysics Data System (ADS)
Gundogdu, O.
Positron Emission Particle Tracking (PEPT) is a powerful non-invasive technique that has been used extensively for tracking a single particle. In this paper, we present a study of zone plate holography method in order to track multiple particles, mainly two particles. The main aim is to use as small number of events as possible in the order to make it possible to track particles in fast moving industrial systems. A zone plate with 100% focal efficiency is simulated and applied to the Positron Emission Tomography (PET) data for multiple particle tracking. A simple trajectory code was employed to explore the effects of the nature of the experimental trajectories. A computer holographic reconstruction code that simulates optical reconstruction was developed. The different aspects of the particle location, particle activity ratios for enabling tagging of particles and zone plate and hologram locations are investigated. The effect of the shot noise is investigated and the limitations of the zone plate holography are reported.
Positron Emission Tomography: Principles, Technology, and Recent Developments
NASA Astrophysics Data System (ADS)
Ziegler, Sibylle I.
Positron emission tomography (PET) is a nuclear medical imaging technique for quantitative measurement of physiologic parameters in vivo (an overview of principles and applications can be found in [P.E. Valk, et al., eds. Positron Emission Tomography. Basic Science and Clinical Practice. 2003, Springer: Heidelberg]), based on the detection of small amounts of posi-tron-emitter-labelled biologic molecules. Various radiotracers are available for neuro-logical, cardiological, and oncological applications in the clinic and in research proto-cols. This overview describes the basic principles, technology, and recent develop-ments in PET, followed by a section on the development of a tomograph with ava-lanche photodiodes dedicated for small animal imaging as an example of efforts in the domain of high resolution tomographs.
Sydenham's chorea: positron emission tomographic (PET) scan studies.
Aron, Alan M
Two patients with Sydenham's chorea were evaluated with positron emission tomographic (PET) scans in the active phase of the disease. One patient had repeat scanning in the recovery phase. PET scans showed hypermetabolic changes of the caudate nuclei and putamen in the active phase of Sydenham's chorea. The scan reverted to normal in the recovery phase. These changes can afford a basis for comparing concurrent serum antibody studies in the acute and recovery phases of Sydenham's chorea.
Positron emission tomographic map reconstruction using fuzzy-median filter
Mondal, Partha Pratim
Positron emission tomography is widely used in medical physics for the reconstruction of the distribution of radionuclei molecules for analyzing regional physiological functions. The existing maximum a posteriori reconstruction methodologies produce artifacts such as oversmoothing and streaking. In this letter, the author proposes a potential function based on fuzzy-median filter for noise-free image reconstruction. The reconstruction methodology is therefore very useful for obtaining artifact-free reconstruction of biomedical specimens.
Development of an improved positron emission particle tracking system
NASA Astrophysics Data System (ADS)
Stellema, C. S.; Vlek, J.; Mudde, R. F.; de Goeij, J. J. M.; van den Bleek, C. M.
An improved Positron Emission Particle Tracking (PEPT) system has been developed for the non-intrusive investigation of solids flow in a gas-solids Interconnected Fluidised Bed (IFB) reactor. This system tracks continuously the 3D location of a single positron emitting particle. This particle has the same size and density as the solids and can be made as small as 500 μm. The system performance was improved through the use of graded absorbers which enable to filter valuable information from the Compton spectrum. A radiotracer particle moving at 1 m s -1 can be located with a 3D resolution better than 15 mm in a continuous trajectory. For a velocity of 0.1 m s -1 the 3D resolution is better than 5 mm. The obtained results are presented through ensemble-averaged solids' velocity patterns.
RPC: from High Energy Physics to Positron Emission Tomography
NASA Astrophysics Data System (ADS)
Belli, G.; DeVecchi, C.; Giroletti, E.; Musitelli, G.; Nardò, R.; Necchi, M. M.; Pagano, D.; Ratti, S. P.; Riccardi, C.; Sani, G.; Torre, P.; Vitulo, P.; Viviani, C.
A low cost gas-based charged particle detector, the Resistive Plate Counter (RPC) intensively used in fixed target and collider high energy experiments, is proposed as basic detector for Positron Emission Tomography. The performance of RPCs in terms of intrinsic space and time resolution and electronic pulse height response, makes it possible to transform standard RPCs into photon detectors and therefore to compensate for the photon sensitivity of scintillating crystals, when the efficiency of the complex crystal + photomultiplier is turned into standard quantum efficiency (q.e). Prototype multigap glass RPCs were developed which optimize γ detection efficiency and thus might substitute the traditional scintillators setups.
Design of a volume-imaging positron emission tomograph
Rogers, J.G.; Coombes, G.H.; Wilkinson, N.A.; Pate, B.D.; Morrison, K.S.; Stazyk, M.; Harrop, R.; Atkins, M.S.; Dykstra, C.J.; Barney, J.S.
Progress is reported in several areas of design of a positron volume imaging tomograph. As a means of increasing the volume imaged and the detector packing fraction, a lens system of detector light coupling is considered. A prototype layered scintillator detector demonstrates improved spatial resolution due to a unique Compton rejection capability.The conceptual design of a new mechanism for measuring scattered radiation during emission scans has been tested by Monte Carlo simulation. The problem of how to use effectively the resulting sampled scattered radiation projections is presented and discussed.
[Positron emission tomography: a new modality in Brazilian nuclear medicine].
Robilotta, Cecil Chow
In nuclear medicine, radioactive substances are used to diagnose and treat disease. This medical specialty, that can provide information about the human body's physiologic and metabolic processes, has become a key diagnostic tool for the early detection of many different disorders, including various types of cancer. The present article describes the historical milestones in nuclear medicine; the basic physical principles underlying positron emission tomography (PET), which is an imaging method used to map the distribution of radiopharmaceuticals in the body for diagnostic and therapeutic purposes, and the current status of this modality in Brazil.
Quantitative simultaneous positron emission tomography and magnetic resonance imaging
Ouyang, Jinsong; Petibon, Yoann; Huang, Chuan; Reese, Timothy G.; Kolnick, Aleksandra L.; El Fakhri, Georges
Abstract. Simultaneous positron emission tomography and magnetic resonance imaging (PET-MR) is an innovative and promising imaging modality that is generating substantial interest in the medical imaging community, while offering many challenges and opportunities. In this study, we investigated whether MR surface coils need to be accounted for in PET attenuation correction. Furthermore, we integrated motion correction, attenuation correction, and point spread function modeling into a single PET reconstruction framework. We applied our reconstruction framework to in vivo animal and patient PET-MR studies. We have demonstrated that our approach greatly improved PET image quality. PMID:26158055
Studying the pulmonary circulation with positron emission tomography
Schuster, D.P.; Mintun, M.A.
Positron emission tomography and appropriately labeled, short-lived radiopharmaceuticals can be used to study a variety of physiologic processes within the lung. Recently, methods have been developed to measure regional pulmonary blood flow and pulmonary vascular permeability to protein macromolecules. The advantages of these techniques include accurate quantitation, regional data available in an image format, noninvasiveness, and repeatability. These methods have recently been applied to studies of hypoxic vasoconstriction, pulmonary edema, and chronic obstructive lung disease in man and large experimental animals. Although the technology is complex and requires the integration of people from a variety of disciplines, these methods offer a unique opportunity to study in vivo lung physiology.
A Semiconductor-Based Positron Emission Tomography System
NASA Astrophysics Data System (ADS)
Oxley, D. C.; Boston, A. J.; Boston, H. C.; Cresswell, J. R.; Grint, A. N.; Harkness, L. J.; Jones, M.; Judson, D. S.; Nolan, P. J.; Slee, M.; Unsworth, C.; Lazarus, I. H.
This paper shall summarize the research conducted employing the high-purity germanium based small animal imaging system, SmartPET (SMall Animal Reconstructive Tomograph for Positron Emission Tomography). Geant4 simulations of the experimental setup were carried out in order to derive novel analysis procedures and quantify the system limitations. In this paper, we will focus on a gamma ray tracking approach devised to overcome germanium's high Compton scattering cross-section and on imaging challenging and complex phantom geometries. The potential of the developed tools and of the system itself will be discussed.
Direct conversion semiconductor detectors in positron emission tomography
NASA Astrophysics Data System (ADS)
Cates, Joshua W.; Gu, Yi; Levin, Craig S.
Semiconductor detectors are playing an increasing role in ongoing research to improve image resolution, contrast, and quantitative accuracy in preclinical applications of positron emission tomography (PET). These detectors serve as a medium for direct detection of annihilation photons. Early clinical translation of this technology has shown improvements in image quality and tumor delineation for head and neck cancers, relative to conventional scintillator-based systems. After a brief outline of the basics of PET imaging and the physical detection mechanisms for semiconductor detectors, an overview of ongoing detector development work is presented. The capabilities of semiconductor-based PET systems and the current state of these devices are discussed.
Positron Emission Tomography imaging with the SmartPET system
NASA Astrophysics Data System (ADS)
Cooper, R. J.; Boston, A. J.; Boston, H. C.; Cresswell, J. R.; Grint, A. N.; Harkness, L. J.; Nolan, P. J.; Oxley, D. C.; Scraggs, D. P.; Mather, A. R.; Lazarus, I.; Simpson, J.
The Small Animal Reconstruction Tomograph for Positron Emission Tomography (SmartPET) project is the development of a small animal Positron Emission Tomography (PET) demonstrator based on the use of High-Purity Germanium (HPGe) detectors and state of the art digital electronics. The experimental results presented demonstrate the current performance of this unique system. By performing high precision measurements of one of the SmartPET HPGe detectors with a range of finely collimated gamma-ray beams the response of the detector as a function of gamma-ray interaction position has been quantified, facilitating the development of parametric Pulse Shape Analysis (PSA) techniques and algorithms for the correction of imperfections in detector performance. These algorithms have then been applied to data from PET imaging measurements using two such detectors in conjunction with a specially designed rotating gantry. In this paper we show how the use of parametric PSA approaches allows over 60% of coincident events to be processed and how the nature and complexity of an event has direct implications for the quality of the resulting image.
Neutrino emissivity from electron-positron annihilation in hot matter in a strong magnetic field
Amsterdamski, P.; Haensel, P. )
The neutrino emissivity due to electron-positron annihilation in a strong magnetic field is computed. A strong magnetic field can significantly increase the neutrino emissivity at {ital T}{similar to}10{sup 9} K.
The Next Generation of Positron Emission Tomography Radiopharmaceuticals in Oncology
Rice, Samuel L.; Roney, Celeste A.; Daumar, Pierre; Lewis, Jason S.
Although 18F-fluorodeoxyglucose (18F-FDG) is still the most widely used positron emission tomography (PET) radiotracer, there are a few well-known limitations to its use. The last decade has seen the development of new PET probes for in vivo visualization of specific molecular targets, along with important technical advances in the production of positron-emitting radionuclides and their related labeling methods. As such, a broad range of new PET tracers are in preclinical development or have recently entered clinical trials. The topics covered in this review include labeling methods, biological targets, and the most recent preclinical or clinical data of some of the next generation of PET radiopharmaceuticals. This review, which is by no means exhaustive, has been separated into sections related to the PET radionuclide used for radiolabeling: fluorine-18, for the labeling of agents such as FACBC, FDHT, choline, and Galacto-RGD; carbon-11, for the labeling of choline; gallium-68, for the labeling of peptides such as DOTATOC and bombesin analogs; and the long-lived radionuclides iodine-124 and zirconium-89 for the labeling of monoclonal antibodies cG250, and J591 and trastuzumab, respectively. PMID:21624561
The next generation of positron emission tomography radiopharmaceuticals in oncology.
Rice, Samuel L; Roney, Celeste A; Daumar, Pierre; Lewis, Jason S
Although (18)F-fluorodeoxyglucose ((18)F-FDG) is still the most widely used positron emission tomography (PET) radiotracer, there are a few well-known limitations to its use. The last decade has seen the development of new PET probes for in vivo visualization of specific molecular targets, along with important technical advances in the production of positron-emitting radionuclides and their related labeling methods. As such, a broad range of new PET tracers are in preclinical development or have recently entered clinical trials. The topics covered in this review include labeling methods, biological targets, and the most recent preclinical or clinical data of some of the next generation of PET radiopharmaceuticals. This review, which is by no means exhaustive, has been separated into sections related to the PET radionuclide used for radiolabeling: fluorine-18, for the labeling of agents such as FACBC, FDHT, choline, and Galacto-RGD; carbon-11, for the labeling of choline; gallium-68, for the labeling of peptides such as DOTATOC and bombesin analogs; and the long-lived radionuclides iodine-124 and zirconium-89 for the labeling of monoclonal antibodies cG250, and J591 and trastuzumab, respectively.
Development of the LBNL positron emission mammography camera
Huber, Jennifer S.; Choong, Woon-Seng; Wang, Jimmy; Maltz, Jonathon S.; Qi, Jinyi; Mandelli, Emanuele; Moses, William W.
We present the construction status of the LBNL Positron Emission Mammography (PEM) camera, which utilizes a PET detector module with depth of interaction measurement consisting of 64 LSO crystals (3x3x30 mm3) coupled on one end to a single photomultiplier tube (PMT) and on the opposite end to a 64 pixel array of silicon photodiodes (PDs). The PMT provides an accurate timing pulse, the PDs identify the crystal of interaction, the sum provides a total energy signal, and the PD/(PD+PMT) ratio determines the depth of interaction. We have completed construction of all 42 PEM detector modules. All data acquisition electronics have been completed, fully tested and loaded onto the gantry. We have demonstrated that all functions of the custom IC work using the production rigid-flex boards and data acquisition system. Preliminary detector module characterization and coincidence data have been taken using the production system, including initial images.
Takakura, Hiroki; Sunada, Kouichi; Shimizu, Kunihiko
A 72-year-old man presented with fever, dyspnea, and weight loss. He was referred to our hospital for further examination of the cause of the pleural effusions. Chest computed tomography showed pleural effusions, a pericardial effusion, and enlarged lymph nodes in the carina tracheae. We administered treatment for heart failure and conducted analyses for a malignant tumor. The pericardial effusion improved, but the pericardium was thickened. Positron emission tomography-computed tomography (PET-CT) showed fluorine-18 deoxyglucose accumulation at the superior fovea of the right clavicle, carina tracheae, superior mediastinum lymph nodes, and a thickened pericardium. Because these findings did not suggest malignancy, we assumed this was a tuberculous lesion. Echocardiography confirmed this finding as constrictive pericarditis; therefore, pericardiolysis was performed. Pathological examination showed features of caseous necrosis and granulomatous changes. Hence, the patient was diagnosed with tuberculous constrictive pericarditis. PET-CT serves as a useful tool for the diagnosis of tuberculous pericarditis. PMID:27263228
A Review on Segmentation of Positron Emission Tomography Images
Foster, Brent; Bagci, Ulas; Mansoor, Awais; Xu, Ziyue; Mollura, Daniel J.
Positron Emission Tomography (PET), a non-invasive functional imaging method at the molecular level, images the distribution of biologically targeted radiotracers with high sensitivity. PET imaging provides detailed quantitative information about many diseases and is often used to evaluate inflammation, infection, and cancer by detecting emitted photons from a radiotracer localized to abnormal cells. In order to differentiate abnormal tissue from surrounding areas in PET images, image segmentation methods play a vital role; therefore, accurate image segmentation is often necessary for proper disease detection, diagnosis, treatment planning, and follow-ups. In this review paper, we present state-of-the-art PET image segmentation methods, as well as the recent advances in image segmentation techniques. In order to make this manuscript self-contained, we also briefly explain the fundamentals of PET imaging, the challenges of diagnostic PET image analysis, and the effects of these challenges on the segmentation results. PMID:24845019
Central Nervous System Drug Evaluation Using Positron Emission Tomography
Maeda, Jun; Shimada, Hitoshi; Nogami, Tsuyoshi; Arakawa, Ryosuke; Takano, Harumasa; Higuchi, Makoto; Ito, Hiroshi; Okubo, Yoshiro; Suhara, Tetsuya
In conventional pharmacological research in the field of mental disorders, pharmacological effect and dose have been estimated by ethological approach and in vitro data of affinity to the site of action. In addition, the frequency of administration has been estimated from drug kinetics in blood. However, there is a problem regarding an objective index of drug effects in the living body. Furthermore, the possibility that the concentration of drug in blood does not necessarily reflect the drug kinetics in target organs has been pointed out. Positron emission tomography (PET) techniques have made progress for more than 20 years, and made it possible to measure the distribution and kinetics of small molecule components in living brain. In this article, we focused on rational drug dosing using receptor occupancy and proof-of-concept of drugs in the drug development process using PET. PMID:23431048
Brain abnormalities in murderers indicated by positron emission tomography.
Raine, A; Buchsbaum, M; LaCasse, L
Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI.
Positron emission tomography (PET) advances in neurological applications
NASA Astrophysics Data System (ADS)
Sossi, V.
Positron Emission Tomography (PET) is a functional imaging modality used in brain research to map in vivo neurotransmitter and receptor activity and to investigate glucose utilization or blood flow patterns both in healthy and disease states. Such research is made possible by the wealth of radiotracers available for PET, by the fact that metabolic and kinetic parameters of particular processes can be extracted from PET data and by the continuous development of imaging techniques. In recent years great advancements have been made in the areas of PET instrumentation, data quantification and image reconstruction that allow for more detailed and accurate biological information to be extracted from PET data. It is now possible to quantitatively compare data obtained either with different tracers or with the same tracer under different scanning conditions. These sophisticated imaging approaches enable detailed investigation of disease mechanisms and system response to disease and/or therapy.
Newer positron emission tomography radiopharmaceuticals for radiotherapy planning: an overview
Mukherjee, Anirban
Positron emission tomography-computed tomography (PET-CT) has changed cancer imaging in the last decade, for better. It can be employed for radiation treatment planning of different cancers with improved accuracy and outcomes as compared to conventional imaging methods. 18F-fluorodeoxyglucose remains the most widely used though relatively non-specific cancer imaging PET tracer. A wide array of newer PET radiopharmaceuticals has been developed for targeted imaging of different cancers. PET-CT with such new PET radiopharmaceuticals has also been used for radiotherapy planning with encouraging results. In the present review we have briefly outlined the role of PET-CT with newer radiopharmaceuticals for radiotherapy planning and briefly reviewed the available literature in this regard. PMID:26904575
Studies of the brain cannabinoid system using positron emission tomography
Gatley, S.J.; Volkow, N.D.
Studies using radiolabeled psychoactive drugs in conjunction with positron emission tomography (PET) have permitted the imaging of binding sites in the human brain. Similar studies of marijuana have been hampered by the unsuitability of radiolabeled THC for PET studies, and the current unavailability of other in vivo imaging agents for cannabinoid receptors. Recent developments in medicinal chemistry suggest that a PET radiotracer for cannabinoid receptors will soon become available. This chapter briefly reviews these developments, together with the results of PET studies of the effects of marijuana and other abused drugs on brain metabolism. It also reviews PET studies of cocaine binding sites, to demonstrate the kind of investigations that will be possible when a cannabinoid receptor PET radioligand becomes available.
Positron Emission Tomography: state of the art and future developments
NASA Astrophysics Data System (ADS)
Pizzichemi, M.
Positron emission tomography (PET) plays a fundamental role in medical imaging, with a wide range of applications covering, among the others, oncology, neurology and cardiology. PET has undergone a steady technological evolution since its introduction in mid 20th century, from the development of 3D PET in the late 1980s, to the invention of PET/CT in the 1990s and more recently with the introduction of PET/MR scanners. The current research topics aiming to develop the next generation of PET scanners are summarized in this paper, focusing on the efforts to increase the sensitivity of the detectors, as long as improving their timing, spatial and energy resolutions, with the final goal of reducing the amount of radioactive dose received by the patients and the duration of the exams while improving at the same time the detectability of lesions.
Resolution and Sensitivity in Positron Emission Tomography Imaging:. New Frontiers
NASA Astrophysics Data System (ADS)
Sossi, V.
The combination of new detector technologies and rapidly increasing computing power is contributing to major developments in positron emission tomography (PET) imaging. The uniqueness of PET resides in its ability to detect very small concentrations of radioactively labeled tracers specifically designed to investigate selected biological functions. The desire to quantitatively observe increasingly complex biological processes together with the need of furthering research in small animal models of disease are pushing the limits of imaging spatial resolution and sensitivity. Resolution of approximately 10 mm3 is now achievable in human size brain scanners, while 1 mm3 can almost be reached in small animal imaging. Such ability will enable a more detailed exploration of healthy and disease function with the ultimate goal of imaging at a molecular level and of detecting pre-clinical disease induced changes.
Differential diagnosis of depression: relevance of positron emission tomography
Schwartz, J.M.; Baxter, L.R. Jr.; Mazziotta, J.C.; Gerner, R.H.; Phelps, M.E.
The proper differential diagnosis of depression is important. A large body of research supports the division of depressive illness into bipolar and unipolar subtypes with respect to demographics, genetics, treatment response, and neurochemical mechanisms. Optimal treatment is different for unipolar and bipolar depressions. Treating a patient with bipolar depression as one would a unipolar patient may precipitate a serious manic episode or possibly even permanent rapid cycling disorder. The clinical distinction between these disorders, while sometimes difficult, can often be achieved through an increased diagnostic suspicion concerning a personal or family history of mania. Positron emission tomography and the FDG method, which allow in vivo study of the glucose metabolic rates for discrete cerebral structures, provide new evidence that bipolar and unipolar depression are two different disorders.
Chelators for copper radionuclides in positron emission tomography radiopharmaceuticals†
Cai, Zhengxin; Anderson, Carolyn J.
The development of chelating agents for copper radionuclides in positron emission tomography radiopharmaceuticals has been a highly active and important area of study in recent years. The rapid evolution of chelators has resulted in highly specific copper chelators that can be readily conjugated to biomolecules and efficiently radiolabeled to form stable complexes in vivo. Chelators are not only designed for conjugation to monovalent biomolecules but also for incorporation into multivalent targeting ligands such as theranostic nanoparticles. These advancements have strengthened the role of copper radionuclides in the fields of nuclear medicine and molecular imaging. This review emphasizes developments of new copper chelators that have most greatly advanced the field of copper-based radiopharmaceuticals over the past 5 years. PMID:24347474
Positron emission tomography for the evaluation and treatment of cardiomyopathy.
Shah, Palak; Choi, Brian G; Mazhari, Ramesh
Congestive heart failure accounts for tremendous morbidity and mortality worldwide. There are numerous causes of cardiomyopathy, the most common of which is coronary artery disease. Positron emission tomography (PET) has an established and expanding role in the evaluation of patients with cardiomyopathy. The specific application of PET to hypertrophic cardiomyopathy, cardiac sarcoidosis, and diabetic cardiomyopathy has been studied extensively and promises to be a useful tool for managing these patients. Furthermore, evaluating the efficacy of standard treatments for congestive heart failure is important as health care costs continue to rise. Recently, there have been significant developments in the field of cardiovascular stem cell research. Familiarity with the mechanisms by which stem cells benefit patients with cardiovascular disease is the key to understanding these advances. Molecular imaging techniques including PET/CT imaging play an important role in monitoring stem cell therapy in both animals and humans. These noninvasive imaging techniques will be highlighted in this paper.
Positron emission tomography in the study of hepatic encephalopathy.
Lockwood, A H
Positron-emission tomography (PET) is a quantitative technique that produces images of biological or physiological processes. The nature of the image depends on the tracer used: common tracers used to study HE include 18F-fluordeoxyglucose, a marker of glucose metabolism; 15O-water, a marker of cerebral blood flow; and 13N-ammonia, a marker of ammonia metabolism. Combined blood flow and ammonia metabolism studies can be used to calculate the permeability surface area product for ammonia at the blood brain barrier. To take full advantage of PET, the data should be analyzed using one of the several sophisticated image processing and analysis techniques that are available. Thus, PET is an ideal technique to evaluate ammonia metabolism and, because of a close linkage of blood flow and glucose metabolism with neural activity, to investigate the neural response to drugs and other treatments and to examine neural systems that mediate specific tasks that are impaired in patients with HE.
Wilson's disease studied with FDG and positron emission tomography
Hawkins, R.A.; Mazziotta, J.C.; Phelps, M.E.
Four patients with Wilson's disease and eight normal controls were studied with 2-deoxy-2-(/sup 18/F)fluoro-D-glucose (FDG) and positron emission tomography (PET). The patients had diffusely reduced glucose metabolism in all brain regions evaluated compared with controls, with the exception of the thalamus. The ratio of the cerebral metabolic rate for glucose in the lenticular nuclei to hemispheres declined from 1.23 (+/- 0.14 SD) in controls to 1.03 (+/- 0.06) (p less than 0.025) in Wilson's disease patients. Compared with Huntington's disease, the PET FDG results in Wilson's disease indicate relatively less focal involvement of the caudate nucleus, more severe focal changes in the lenticular nuclei, and more significant global changes in glucose metabolism.
Integrated telemedicine applications and services for oncological positron emission tomography.
Kontaxakis, George; Visvikis, Dimitris; Ohl, Roland; Sachpazidis, Ilias; Suarez, Juan Pablo; Selby, Peter; Cheze-Le Rest, Catherine; Santos, Andres; Ortega, Fernando; Diaz, Javier; Pan, Leyun; Strauss, Ludwig; Dimitrakopoulou-Strauss, Antonia; Sakas, Georgios; Pozo, Miguel Angel
TENPET (Trans European Network for Positron Emission Tomography) aims to evaluate the provision of integrated teleconsultation and intelligent computer supported cooperative work services for clinical positron emission tomography (PET) in Europe at its current stage, as it is a multi-centre project financially supported by the European Commission (Information Society, eTEN Program). It addresses technological challenges by linking PET centres and developing supporting services that permit remote consultation between professionals in the field. The technological platform (CE-marked) runs on Win2000/NT/XP systems and incorporates advanced techniques for image visualization, analysis and fusion, as well as for interactive communication and message handling for off-line communications. Four PET Centres from Spain, France and Germany participate to the pilot system trials. The performance evaluation of the system is carried out via log files and user-filled questionnaires on the frequency of the teleconsultations, their duration and efficacy, quality of the images received, user satisfaction, as well as on privacy, ethical and security issues. TENPET promotes the co-operation and improved communication between PET practitioners that are miles away from their peers or on mobile units, offering options for second opinion and training and permitting physicians to remotely consult patient data if they are away from their centre. It is expected that TENPET will have a significant impact in the development of new skills by PET professionals and will support the establishment of peripheral PET units. To our knowledge, TENPET is the first telemedicine service specifically designed for oncological PET. This report presents the technical innovations incorporated in the TENPET platform and the initial pilot studies at real and diverse clinical environments in the field of oncology.
Positron emission tomography in the study of human tumors.
Beaney, R P
To increase our understanding of cancer and improve cancer treatment on a rational basis we need to identify both qualitative and quantitative differences between normal and neoplastic tissue. The multimodality approach to cancer treatment includes radiotherapy, chemotherapy, hyperthermia, and immunotherapy. Most of the data on which we base our therapeutic strategies have been derived from in vitro studies or animal tumor models. More information is required on the physiology of in vivo human tumors and their response to therapy. Positron emission tomography allows the regional tissue concentration of a positron emitting radionuclide to be measured in absolute units. If valid tracer models can be formulated that accurately describe the fate of an administered "biological" tracer then the physiological process under investigation can be measured quantitatively. The sequential inhalation of C15O2, 15O2, and 11CO allows regional tissue blood flow, oxygen utilization and blood volume to be measured in absolute units. Tissue perfusion, a measure of nutrient (eg, oxygen) supply, drug delivery, or a means of heat dissipation, is of immense importance to oncologists. The oxygen-15 technique has been used not only to study regional blood flow and oxygen utilization in both tumor and normal tissue but also their response to therapeutic intervention. In those studies were tracer models are thought to be less than complete (eg, due to insufficient biological data) then only a semiquantitative or qualitative assessment of the pathophysiological state may be possible. In this respect, tumor function has been characterized by the rate of uptake of 18F-2-deoxyglucose. This technique has provided a means of tumor grading and differentiating between radiation-induced tissue necrosis and tumor recurrence. Metabolic imaging with labeled amino acids appears particularly useful in the delineation of tumor extent. Blood brain barrier integrity and the pharmacokinetics of cytotoxic drugs
Production of the PET bone agent (18)F-fluoride ion, simultaneously with (18)F-FDG by a single run of the medical cyclotron with minimal radiation exposure- a novel technique.
Kumar, Rajeev; Sonkawade, Rajendra G; Tripathi, Madhavi; Sharma, Punit; Gupta, Priyanka; Kumar, Praveen; Pandey, Anil K; Bal, Chandrasekhar; Damle, Nishikant Avinash; Bandopadhayaya, Gurupad
Our aim was to establish an easy and convenient procedure for the preparation of fluorine-18-sodium fluoride ((18)F-NaF) for bone positron emission tomography (PET) during routine (18)F-FDG production using the Explora FDG4 radiochemistry module (EFRM) by single run of Cyclotron with negligible radiation exposure. We compared three techniques for (18)F-NaF production during routine PET radiochemistry at our setup. In one method we used synthesis module and in other two methods we did not. In the first and third method, F-18 was directly extracted from the V-vial and in the second method, (18)F-NaF was extracted by post processing from the EFRM. In the first method, F-18 was extracted directly from V-vial manually by opening the V-vial cap. In the second method, Explora FDG-4 Module was used. First, F-18 was transferred from the V-vial. Then, after post processing in EFRM, pure F-18 was obtained in the product vial. In the third method, pure F-18 was obtained in the product vial with the help of a mechanical robotic arm. The above were followed by routine quality control of (18)F-NaF produced by each method. Results of quality control of the (18)F-NaF obtained by all three methods satisfied all parameters prescribed by the United States Pharmacopeia (USP) and the British Pharmacopeia (BP) including biological, physical and chemical specifications. The radiochemical purity was 98.5±1.5% with Rf 0.006. The level of Kryptofix-222 (K222) in (18)F-NaF was within the prescribed limit. Mean pH of (18)F-NaF was 6.0±1.5. The exposure rate around the hot cell was negligible. In conclusion, from the results it was obvious that by our method number three (18)F-NaF was directly obtained from the V-vial using mechanical robotic arms. This method was the most appropriate with minimized radiation exposure to the handling Radiochemist and was also saving time as compared to the other two methods.
Simultaneous iterative reconstruction of emission and attenuation images in positron emission tomography from emission data only.
Landmann, M; Reske, S N; Glatting, G
For quantitative image reconstruction in positron emission tomography attenuation correction is mandatory. In case that no data are available for the calculation of the attenuation correction factors one can try to determine them from the emission data alone. However, it is not clear if the information content is sufficient to yield an adequate attenuation correction together with a satisfactory activity distribution. Therefore, we determined the log likelihood distribution for a thorax phantom depending on the choice of attenuation and activity pixel values to measure the crosstalk between both. In addition an iterative image reconstruction (one-dimensional Newton-type algorithm with a maximum likelihood estimator), which simultaneously reconstructs the images of the activity distribution and the attenuation coefficients is used to demonstrate the problems and possibilities of such a reconstruction. As result we show that for a change of the log likelihood in the range of statistical noise, the associated change in the activity value of a structure is between 6% and 263%. In addition, we show that it is not possible to choose the best maximum on the basis of the log likelihood when a regularization is used, because the coupling between different structures mediated by the (smoothing) regularization prevents an adequate solution due to crosstalk. We conclude that taking into account the attenuation information in the emission data improves the performance of image reconstruction with respect to the bias of the activities, however, the reconstruction still is not quantitative.
Positron emission tomography radiopharmaceuticals for imaging brain Beta-amyloid.
Vallabhajosula, Shankar
Alzheimer's disease (AD) is defined histologically by the presence of extracellular β-amyloid (Aβ) plaques and intraneuronal neurofibrillary tangles in the cerebral cortex. The diagnosis of dementia, along with the prediction of who will develop dementia, has been assisted by magnetic resonance imaging and positron emission tomography (PET) by using [(18)F]fluorodeoxyglucose (FDG). These techniques, however, are not specific for AD. Based on the chemistry of histologic staining dyes, several Aβ-specific positron-emitting radiotracers have been developed to image neuropathology of AD. Among these, [(11)C]PiB is the most studied Aβ-binding PET radiopharmaceutical in the world. The histologic and biochemical specificity of PiB binding across different regions of the AD brain was demonstrated by showing a direct correlation between Aβ-containing amyloid plaques and in vivo [(11)C]PiB retention measured by PET imaging. Because (11)C is not ideal for commercialization, several (18)F-labeled tracers have been developed. At this time, [(18)F]3'-F-PiB (Flutemetamol), (18)F-AV-45 (Florbetapir), and (18)F-AV-1 (Florbetaben) are undergoing extensive phase II and III clinical trials. This article provides a brief review of the amyloid biology and chemistry of Aβ-specific (11)C and (18)F-PET radiopharmaceuticals. Clinical trials have clearly documented that PET radiopharmaceuticals capable of assessing Aβ content in vivo in the brains of AD subjects and subjects with mild cognitive impairment will be important as diagnostic agents to detect in vivo amyloid brain pathology. In addition, PET amyloid imaging will also help test the amyloid cascade hypothesis of AD and as an aid to assess the efficacy of antiamyloid therapeutics currently under development in clinical trials.
Positron emission tomography provides molecular imaging of biological processes
Phelps, Michael E.
Diseases are biological processes, and molecular imaging with positron emission tomography (PET) is sensitive to and informative of these processes. This is illustrated by detection of biological abnormalities in neurological disorders with no computed tomography or MRI anatomic changes, as well as even before symptoms are expressed. PET whole body imaging in cancer provides the means to (i) identify early disease, (ii) differentiate benign from malignant lesions, (iii) examine all organs for metastases, and (iv) determine therapeutic effectiveness. Diagnostic accuracy of PET is 8–43% higher than conventional procedures and changes treatment in 20–40% of the patients, depending on the clinical question, in lung and colorectal cancers, melanoma, and lymphoma, with similar findings in breast, ovarian, head and neck, and renal cancers. A microPET scanner for mice, in concert with human PET systems, provides a novel technology for molecular imaging assays of metabolism and signal transduction to gene expression, from mice to patients: e.g., PET reporter gene assays are used to trace the location and temporal level of expression of therapeutic and endogenous genes. PET probes and drugs are being developed together—in low mass amounts, as molecular imaging probes to image the function of targets without disturbing them, and in mass amounts to modify the target's function as a drug. Molecular imaging by PET, optical technologies, magnetic resonance imaging, single photon emission tomography, and other technologies are assisting in moving research findings from in vitro biology to in vivo integrative mammalian biology of disease. PMID:10922074
[Positron emission tomography (PET) in malignant ovarian tumors].
Fularz, Maciej; Adamiak, Paulina; Czepczyński, Rafał; Jarzabek-Bielecka, Grazyna; Kedzia, Witold; Ruchała, Marek
Accessibility of positron emission tomography integrated with computed tomography (PET/CT) has improved significantly in recent years. PET/CT with the use of 18F-deoxyglucose (FDG) is widely used in patients with ovarian malignancies at different stages of the management. FDG PET/CT shows high diagnostic accuracy in the differentiation of benign and malignant ovarian lesions with the exception of borderline tumors that may cause false negative results. Moreover FDG PET/CT is used in some centers for preoperative staging and determining the prognosis of ovarian cancer However further studies including larger groups of patients are needed to confirm the applicability of FDG PET/CT in case of the two abovementioned indications. Until now, the best documented indication for FDG PET/ CT in patients with ovarian cancer has been the detection of recurrence, especially in subjects with elevated CA 125 marker and negative results of other imaging techniques. This review focuses on the applicability of PET with the use of FDG in ovarian malignancies and points out to the limitations of this method.
Regulation of the compounding of positron emission tomography drugs.
Hung, J C
Controversial aspects of the regulatory framework for compounding drug products used in positron emission tomography (PET) are discussed. The Food and Drug Administration Modernization Act of 1997 (FDAMA), which amends the Federal Food, Drug, and Cosmetic Act (FFDCA), required that FDA establish approval (new drug application [NDA] and abbreviated new drug application [ANDA]) procedures and current good manufacturing practice (CGMP) requirements for PET drugs; this seems to conflict with differentiation between manufacturing and compounding in FFDCA. Compounding by pharmacists is implied in the FDAMA section on PET, but specific mention of "pharmacist" needs to be included. Congress apparently did not intend for compounded PET drugs to be regulated differently from other drugs. Although FDA has waived NDA and ANDA fees for three PET radiopharmaceuticals, revision of FDAMA to exempt PET drug products from regulations placed on manufacturing is needed. Without relief from the current regulations, many academic PET centers are likely to close; this would violate FDAMA's stated intent of making PET available to patients at reasonable cost. Also problematic is FDAMA's prohibition of compounding "regularly or in inordinate amounts" a product that is commercially available; the common PET radiopharmaceutical fludeoxyglucose F 18 injection, for example, is commercially available. A sensible alternative to NDA or ANDA and CGMP requirements would be the enforcement of USP standards for PET drugs by state boards of pharmacy.
Therapy response evaluation with positron emission tomography-computed tomography.
Segall, George M
Positron emission tomography-computed tomography with F-18-fluorodeoxyglucose is widely used for evaluation of therapy response in patients with solid tumors but has not been as readily adopted in clinical trials because of the variability of acquisition and processing protocols and the absence of universal response criteria. Criteria proposed for clinical trials are difficult to apply in clinical practice, and gestalt impression is probably accurate in individual patients, especially with respect to the presence of progressive disease and complete response. Semiquantitative methods of determining tissue glucose metabolism, such as standard uptake value, can be a useful descriptor for levels of tissue glucose metabolism and changes in response to therapy if technical quality control measures are carefully maintained. The terms partial response, complete response, and progressive disease are best used in clinical trials in which the terms have specific meanings and precise definitions. In clinical practice, it may be better to use descriptive terminology agreed upon by imaging physicians and clinicians in their own practice. PMID:21147376
European health telematics networks for positron emission tomography
NASA Astrophysics Data System (ADS)
Kontaxakis, George; Pozo, Miguel Angel; Ohl, Roland; Visvikis, Dimitris; Sachpazidis, Ilias; Ortega, Fernando; Guerra, Pedro; Cheze-Le Rest, Catherine; Selby, Peter; Pan, Leyun; Diaz, Javier; Dimitrakopoulou-Strauss, Antonia; Santos, Andres; Strauss, Ludwig; Sakas, Georgios
A pilot network of positron emission tomography centers across Europe has been setup employing telemedicine services. The primary aim is to bring all PET centers in Europe (and beyond) closer, by integrating advanced medical imaging technology and health telematics networks applications into a single, easy to operate health telematics platform, which allows secure transmission of medical data via a variety of telecommunications channels and fosters the cooperation between professionals in the field. The platform runs on PCs with Windows 2000/XP and incorporates advanced techniques for image visualization, analysis and fusion. The communication between two connected workstations is based on a TCP/IP connection secured by secure socket layers and virtual private network or jabber protocols. A teleconsultation can be online (with both physicians physically present) or offline (via transmission of messages which contain image data and other information). An interface sharing protocol enables online teleconsultations even over low bandwidth connections. This initiative promotes the cooperation and improved communication between nuclear medicine professionals, offering options for second opinion and training. It permits physicians to remotely consult patient data, even if they are away from the physical examination site.
Silicon as an unconventional detector in positron emission tomography
NASA Astrophysics Data System (ADS)
Clinthorne, Neal; Brzezinski, Karol; Chesi, Enrico; Cochran, Eric; Grkovski, Milan; Grošičar, Borut; Honscheid, Klaus; Huh, Sam; Kagan, Harris; Lacasta, Carlos; Linhart, Vladimir; Mikuž, Marko; Smith, D. Shane; Stankova, Vera; Studen, Andrej; Weilhammer, Peter; Žontar, Dejan
Positron emission tomography (PET) is a widely used technique in medical imaging and in studying small animal models of human disease. In the conventional approach, the 511 keV annihilation photons emitted from a patient or small animal are detected by a ring of scintillators such as LYSO read out by arrays of photodetectors. Although this has been successful in achieving ˜5 mm FWHM spatial resolution in human studies and ˜1 mm resolution in dedicated small animal instruments, there is interest in significantly improving these figures. Silicon, although its stopping power is modest for 511 keV photons, offers a number of potential advantages over more conventional approaches including the potential for high intrinsic spatial resolution in 3D. To evaluate silicon in a variety of PET "magnifying glass" configurations, an instrument was constructed that consists of an outer partial-ring of PET scintillation detectors into which various arrangements of silicon detectors are inserted to emulate dual-ring or imaging probe geometries. Measurements using the test instrument demonstrated the capability of clearly resolving point sources of 22Na having a 1.5 mm center-to-center spacing as well as the 1.2 mm rods of a 18F-filled resolution phantom. Although many challenges remain, silicon has potential to become the PET detector of choice when spatial resolution is the primary consideration.
Geoscientific process monitoring with positron emission tomography (GeoPET)
NASA Astrophysics Data System (ADS)
Kulenkampff, Johannes; Gründig, Marion; Zakhnini, Abdelhamid; Lippmann-Pipke, Johanna
Transport processes in geomaterials can be observed with input-output experiments, which yield no direct information on the impact of heterogeneities, or they can be assessed by model simulations based on structural imaging using µ-CT. Positron emission tomography (PET) provides an alternative experimental observation method which directly and quantitatively yields the spatio-temporal distribution of tracer concentration. Process observation with PET benefits from its extremely high sensitivity together with a resolution that is acceptable in relation to standard drill core sizes. We strongly recommend applying high-resolution PET scanners in order to achieve a resolution on the order of 1 mm. We discuss the particularities of PET applications in geoscientific experiments (GeoPET), which essentially are due to high material density. Although PET is rather insensitive to matrix effects, mass attenuation and Compton scattering have to be corrected thoroughly in order to derive quantitative values. Examples of process monitoring of advection and diffusion processes with GeoPET illustrate the procedure and the experimental conditions, as well as the benefits and limits of the method.
Florbetapir positron emission tomography and cerebrospinal fluid biomarkers
Hake, Ann; Trzepacz, Paula T.; Wang, Shufang; Yu, Peng; Case, Michael; Hochstetler, Helen; Witte, Michael M.; Degenhardt, Elisabeth K.; Dean, Robert A.
Background We evaluated the relationship between florbetapir-F18 positron emission tomography (FBP PET) and cerebrospinal fluid (CSF) biomarkers. Methods Alzheimer's Disease Neuroimaging Initiative (ADNI)-GO/2 healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia subjects with clinical measures and CSF collected ±90 days of FBP PET data were analyzed using correlation and logistic regression. Results In HC and MCI subjects, FBP PET anterior and posterior cingulate and composite standard uptake value ratios correlated with CSF amyloid beta (Aβ1-42) and tau/Aβ1-42 ratios. Using logistic regression, Aβ1-42, total tau (t-tau), phosphorylated tau181P (p-tau), and FBP PET composite each differentiated HC versus AD. Aβ1-42 and t-tau distinguished MCI versus AD, without additional contribution by FBP PET. Total tau and p-tau added discriminative power to FBP PET when classifying HC versus AD. Conclusion Based on cross-sectional diagnostic groups, both amyloid and tau measures distinguish healthy from demented subjects. Longitudinal analyses are needed. PMID:25916563
Eyeblink Conditioning in Healthy Adults: A Positron Emission Tomography Study
Andreasen, Nancy C.; Liu, Dawei; Freeman, John H.; Boles Ponto, Laura L.; O'Leary, Daniel S.
Eyeblink conditioning is a paradigm commonly used to investigate the neural mechanisms underlying motor learning. It involves the paired presentation of a toneconditioning stimulus which precedes and co-terminates with an airpuff unconditioned stimulus. Following repeated paired presentations a conditioned eyeblink develops which precedes the airpuff. This type of learning has been intensively studied and the cerebellum is known to be essential in both humans and animals. The study presented here was designed to investigate the role of the cerebellum during eyeblink conditioning in humans using positron emission tomography (PET). The sample includes 20 subjects (10 male and 10 female) with an average age of 29.2 years. PET imaging was used to measure regional cerebral blood flow (rCBF) changes occurring during the first, second, and third blocks of conditioning. In addition, stimuli-specific rCBF to unpaired tones and airpuffs ("pseudoconditioning") was used as a baseline level that was subtracted from each block. Conditioning was performed using three, 15-trial blocks of classical eyeblink conditioning with the last five trials in each block imaged. As expected, subjects quickly acquired conditioned responses. A comparison between the conditioning tasks and the baseline task revealed that during learning there was activation of the cerebellum and recruitment of several higher cortical regions. Specifically, large peaks were noted in cerebellar lobules IV/V, the frontal lobes, and cingulate gyri. PMID:22430943
Imaging pancreatic islet cells by positron emission tomography
Li, Junfeng; Karunananthan, Johann; Pelham, Bradley; Kandeel, Fouad
It was estimated that every year more than 30000 persons in the United States - approximately 80 people per day - are diagnosed with type 1 diabetes (T1D). T1D is caused by autoimmune destruction of the pancreatic islet (β cells) cells. Islet transplantation has become a promising therapy option for T1D patients, while the lack of suitable tools is difficult to directly evaluate of the viability of the grafted islet over time. Positron emission tomography (PET) as an important non-invasive methodology providing high sensitivity and good resolution, is able to accurate detection of the disturbed biochemical processes and physiological abnormality in living organism. The successful PET imaging of islets would be able to localize the specific site where transplanted islets engraft in the liver, and to quantify the level of islets remain alive and functional over time. This information would be vital to establishing and evaluating the efficiency of pancreatic islet transplantation. Many novel imaging agents have been developed to improve the sensitivity and specificity of PET islet imaging. In this article, we summarize the latest developments in carbon-11, fluorine-18, copper-64, and gallium-68 labeled radioligands for the PET imaging of pancreatic islet cells. PMID:27721939
Positron Emission Tomography Detector Development for Plant Biology
Weisenberger, A G; McKisson, J; Stolin, A; Zorn, C; Howell, C R; Crowell, A S; Reid, C D; Majewski, S; Smith, M F
There are opportunities for the development of new tools to advance plant biology research through the use of radionuclides. Thomas Jefferson National Accelerator Facility, Duke University, West Virginia University and the University of Maryland are collaborating on the development of radionuclide imaging technologies to facilitate plant biology research. Biological research into optimizing plant productivity under various environmental constraints, biofuel and carbon sequestration research are areas that could potentially benefit from new imaging technologies. Using 11CO2 tracers, the investigators at Triangle University Nuclear Laboratory / Duke University Phytotron are currently researching the dynamical responses of plants to environmental changes forecasted from increasing greenhouse trace gases involved in global change. The biological research primary focus is to investigate the impact of elevated atmospheric CO2 and nutrients limitation on carbon and nitrogen dynamics in plants. We report here on preliminary results of 11CO2 plant imaging experiments involving barley plants using Jefferson Lab dual planar positron emission tomography detectors to image 11CO2 in live barley plants. New detector designs will be developed based on the preliminary studies reported here and further planned.
The methodology of TSPO imaging with positron emission tomography.
Turkheimer, Federico E; Rizzo, Gaia; Bloomfield, Peter S; Howes, Oliver; Zanotti-Fregonara, Paolo; Bertoldo, Alessandra; Veronese, Mattia
The 18-kDA translocator protein (TSPO) is consistently elevated in activated microglia of the central nervous system (CNS) in response to a variety of insults as well as neurodegenerative and psychiatric conditions. It is therefore a target of interest for molecular strategies aimed at imaging neuroinflammation in vivo. For more than 20 years, positron emission tomography (PET) has allowed the imaging of TSPO density in brain using [(11)C]-(R)-PK11195, a radiolabelled-specific antagonist of the TSPO that has demonstrated microglial activation in a large number pathological cohorts. The significant clinical interest in brain immunity as a primary or comorbid factor in illness has sparked great interest in the TSPO as a biomarker and a surprising number of second generation TSPO radiotracers have been developed aimed at improving the quality of TSPO imaging through novel radioligands with higher affinity. However, such major investment has not yet resulted in the expected improvement in image quality. We here review the main methodological aspects of TSPO PET imaging with particular attention to TSPO genetics, cellular heterogeneity of TSPO in brain tissue and TSPO distribution in blood and plasma that need to be considered in the quantification of PET data to avoid spurious results as well as ineffective development and use of these radiotracers.
Simultaneous laser speckle imaging and positron emission tomography
NASA Astrophysics Data System (ADS)
Gramer, M.; Feuerstein, D.; Backes, H.; Takagaki, M.; Kumagai, T.; Graf, R.
Complex biological systems often require measurements of multiple parameters with high temporal and spatial resolution. Multimodal approaches and the combination of methods are therefore a powerful tool to address such scientific questions. Laser speckle imaging (LSI) is an optical method that monitors dynamic changes in cortical blood flow (CBF) with high temporal resolution. Positron emission tomography (PET) allows for quantitative imaging of physiological processes and is a gold standard method to determine absolute cerebral blood flow. We developed a setup that allows simultaneous measurement with both modalities. Here, we simultaneously measured CBF with PET and LSI in rats and analyzed how the correlation of PET and LSI is modified when (1) different methods are used for the calculation of speckle inverse correlation time (ICT), (2) speckle data is acquired through thinned or craniectomized skull, (3) influence of surface vessels is removed from the speckle data. For the latter, a method for automated vessel segmentation from LSI data was developed. We obtained the best correlation (R² = 0.890, p<0.001) when correcting for surface vessel structures taking into account the contribution of static scatterers while keeping the coherence factor constant. However, using the originally published relation, which allows a 900 times faster computation of blood flow maps, still provided a good correlation (R2 = 0.879, p<0.001). Given the good correlation between LSI and PET we used our data to calibrate the speckle ICT. Thus, LSI provides CBF in absolute units at high temporal resolution.
Characterization of nontransmural myocardial infarction by positron-emission tomography
Geltman, E.M.; Biello, D.; Welch, M.J.; Ter-Pogossian, M.M.; Roberts, R.; Sobel, B.E.
The present study was performed to determine whether positron emission tomography (PET) performed after i.v. 11C-palmitate permits detection and characterization of nontransmural myocardial infarction. PET was performed after the i.v. injection of 11C-palmitate in 10 normal subjects, 24 patients with initial nontransmural myocardial infarction (defined electrocardiographically), and 22 patients with transmural infarction. Depressed accumulation of 11C-palmitate was detected with sagittal, coronal and transverse reconstructions, and quantified based on 14 contiguous transaxial reconstructions. Defects with homogeneously intense depression of accumulation of tracer were detected in all 22 patients with transmural infarction (100%). Abnormalities of the distribution of 11C-palmitate in the myocardium were detected in 23 patients with nontransmural infarction (96%). Thallium scintigrams were abnormal in only 11 of 18 patients with nontransmural infarction (61%). Tomographically estimated infarct size was greater among patients with transmural infarction (50.4 +/- 7.8 PET-g-Eq/m2 (+/- SEM SEM)) compared with those with nontransmural infarction (19 +/- 4 PET-g-Eq, p less than 0.01). Residual accumulation of 11C-palmitate within regions of infarction was more intensely depressed among patients with transmural compared to nontransmural infarction (33 +/- 1 vs 39 +/- 1% maximal myocardial radioactivity, p less than 0.01). Thus, PET and metabolic imaging with 11C-palmitate is a sensitive means of detecting, quantifying and characterizing nontransmural and transmural myocardial infarction.
Usefulness of Positron Emission Tomographic Studies for Gliomas
MIYAKE, Keisuke; OGAWA, Daisuke; OKADA, Masaki; HATAKEYAMA, Tetsuhiro; TAMIYA, Takashi
Non-invasive positron emission tomography (PET) enables the measurement of metabolic and molecular processes with high sensitivity. PET plays a significant role in the diagnosis, prognosis, and treatment of brain tumors and predominantly detects brain tumors by detecting their metabolic alterations, including energy metabolism, amino acids, nucleic acids, and hypoxia. Glucose metabolic tracers are related to tumor cell energy and exhibit good sensitivity but poor specificity for malignant tumors. Amino acid metabolic tracers provide a better delineation of tumors and cellular proliferation. Nucleic acid metabolic tracers have a high sensitivity for malignant tumors and cellular proliferation. Hypoxic metabolism tracers are useful for detecting resistance to radiotherapy and chemotherapy. Therefore, PET imaging techniques are useful for detecting biopsy-targeting points, deciding on tumor resection, radiotherapy planning, monitoring therapy, and distinguishing brain tumor recurrence or progression from post-radiotherapy effects. However, it is not possible to use only one PET tracer to make all clinical decisions because each tracer has both advantages and disadvantages. This study focuses on the different kinds of PET tracers and summarizes their recent applications in patients with gliomas. Combinational uses of PET tracers are expected to contribute to differential diagnosis, prognosis, treatment targeting, and monitoring therapy. PMID:27250577
Quantifying the limitations of small animal positron emission tomography
NASA Astrophysics Data System (ADS)
Oxley, D. C.; Boston, A. J.; Boston, H. C.; Cooper, R. J.; Cresswell, J. R.; Grint, A. N.; Nolan, P. J.; Scraggs, D. P.; Lazarus, I. H.; Beveridge, T. E.
The application of position sensitive semiconductor detectors in medical imaging is a field of global research interest. The Monte-Carlo simulation toolkit GEANT4 [ http://geant4.web.cern.ch/geant4/] was employed to improve the understanding of detailed γ-ray interactions within the small animal Positron Emission Tomography (PET), high-purity germanium (HPGe) imaging system, SmartPET [A.J. Boston, et al., Oral contribution, ANL, Chicago, USA, 2006]. This system has shown promising results in the field of PET [R.J. Cooper, et al., Nucl. Instr. and Meth. A (2009), accepted for publication] and Compton camera imaging [J.E. Gillam, et al., Nucl. Instr. and Meth. A 579 (2007) 76]. Images for a selection of single and multiple point, line and phantom sources were successfully reconstructed using both a filtered-back-projection (FBP) [A.R. Mather, Ph.D. Thesis, University of Liverpool, 2007] and an iterative reconstruction algorithm [A.R. Mather, Ph.D. Thesis, University of Liverpool, 2007]. Simulated data were exploited as an alternative route to a reconstructed image allowing full quantification of the image distortions introduced in each phase of the data processing. Quantifying the contribution of uncertainty in all system components from detector to reconstruction algorithm allows the areas in need of most attention on the SmartPET project and semiconductor PET to be addressed.
Microfluidics for Positron Emission Tomography (PET) Imaging Probe Development
Wang, Ming-Wei; Lin, Wei-Yu; Liu, Kan; Masterman-Smith, Michael; Shen, Clifton Kwang-Fu
Due to increased needs for Positron Emission Tomography (PET) scanning, high demands for a wide variety of radiolabeled compounds will have to be met by exploiting novel radiochemistry and engineering technologies to improve the production and development of PET probes. The application of microfluidic reactors to perform radiosyntheses is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional labeling systems. Microfluidic-based radiochemistry can lead to the use of smaller quantities of precursors, accelerated reaction rates and easier purification processes with greater yield and higher specific activity of desired probes. Several 'proof-of-principle' examples, along with basics of device architecture and operation, and potential limitations of each design are discussed here. Along with the concept of radioisotope distribution from centralized cyclotron facilities to individual imaging centers and laboratories ("decentralized model"), an easy-to-use, standalone, flexible, fully-automated radiochemical microfluidic platform can open up to simpler and more cost-effective procedures for molecular imaging using PET. PMID:20643021
Automated identification of the lung contours in positron emission tomography
NASA Astrophysics Data System (ADS)
Nery, F.; Silvestre Silva, J.; Ferreira, N. C.; Caramelo, F. J.; Faustino, R.
Positron Emission Tomography (PET) is a nuclear medicine imaging technique that permits to analyze, in three dimensions, the physiological processes in vivo. One of the areas where PET has demonstrated its advantages is in the staging of lung cancer, where it offers better sensitivity and specificity than other techniques such as CT. On the other hand, accurate segmentation, an important procedure for Computer Aided Diagnostics (CAD) and automated image analysis, is a challenging task given the low spatial resolution and the high noise that are intrinsic characteristics of PET images. This work presents an algorithm for the segmentation of lungs in PET images, to be used in CAD and group analysis in a large patient database. The lung boundaries are automatically extracted from a PET volume through the application of a marker-driven watershed segmentation procedure which is robust to the noise. In order to test the effectiveness of the proposed method, we compared the segmentation results in several slices using our approach with the results obtained from manual delineation. The manual delineation was performed by nuclear medicine physicians that used a software routine that we developed specifically for this task. To quantify the similarity between the contours obtained from the two methods, we used figures of merit based on region and also on contour definitions. Results show that the performance of the algorithm was similar to the performance of human physicians. Additionally, we found that the algorithm-physician agreement is similar (statistically significant) to the inter-physician agreement.
76 FR 47593 - Guidance for Small Business Entities on Current Good Manufacturing Practice for Positron Emission...
Federal Register 2010, 2011, 2012, 2013, 2014
... Manufacturing Practice for Positron Emission Tomography Drugs; Availability AGENCY: Food and Drug Administration... a guidance for small business entities entitled ``PET Drugs--Current Good Manufacturing Practice... entitled ``PET Drugs--Current Good Manufacturing Practice (CGMP); Small Entity Compliance Guide.''...
77 FR 71802 - Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...
Federal Register 2010, 2011, 2012, 2013, 2014
... HUMAN SERVICES Food and Drug Administration Guidance on Investigational New Drug Applications for... ``Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs.'' The guidance is intended to assist manufacturers of PET drugs in submitting investigational new drug applications (INDs)....
Fuzzy-rule-based image reconstruction for positron emission tomography
NASA Astrophysics Data System (ADS)
Mondal, Partha P.; Rajan, K.
Positron emission tomography (PET) and single-photon emission computed tomography have revolutionized the field of medicine and biology. Penalized iterative algorithms based on maximum a posteriori (MAP) estimation eliminate noisy artifacts by utilizing available prior information in the reconstruction process but often result in a blurring effect. MAP-based algorithms fail to determine the density class in the reconstructed image and hence penalize the pixels irrespective of the density class. Reconstruction with better edge information is often difficult because prior knowledge is not taken into account. The recently introduced median-root-prior (MRP)-based algorithm preserves the edges, but a steplike streaking effect is observed in the reconstructed image, which is undesirable. A fuzzy approach is proposed for modeling the nature of interpixel interaction in order to build an artifact-free edge-preserving reconstruction. The proposed algorithm consists of two elementary steps: (1) edge detection, in which fuzzy-rule-based derivatives are used for the detection of edges in the nearest neighborhood window (which is equivalent to recognizing nearby density classes), and (2) fuzzy smoothing, in which penalization is performed only for those pixels for which no edge is detected in the nearest neighborhood. Both of these operations are carried out iteratively until the image converges. Analysis shows that the proposed fuzzy-rule-based reconstruction algorithm is capable of producing qualitatively better reconstructed images than those reconstructed by MAP and MRP algorithms. The reconstructed images are sharper, with small features being better resolved owing to the nature of the fuzzy potential function.
Simultaneous iterative reconstruction for emission and attenuation images in positron emission tomography.
Glatting, G; Wuchenauer, M; Reske, S N
The quality of the attenuation correction strongly influences the outcome of the reconstructed emission scan in positron emission tomography. Usually the attenuation correction factors are calculated from the transmission and blank scan and thereafter applied during the reconstruction on the emission data. However, this is not an optimal treatment of the available data, because the emission data themselves contain additional information about attenuation: The optimal treatment must use this information for the determination of the attenuation correction factors. Therefore, our purpose is to investigate a simultaneous emission and attenuation image reconstruction using a maximum likelihood estimator, which takes the attenuation information in the emission data into account. The total maximum likelihood function for emission and transmission is used to derive a one-dimensional Newton-like algorithm for the calculation of the emission and attenuation image. Log-likelihood convergence, mean differences, and the mean of squared differences for the emission image and the attenuation correction factors of a mathematical thorax phantom were determined and compared. As a result we obtain images improved with respect to log likelihood in all cases and with respect to our figures of merit in most cases. We conclude that the simultaneous reconstruction can improve the performance of image reconstruction.
Positron emission tomography: a first-hand experience.
Traylor, J
In July 1999, the University of Kansas Hospital installed a positron emission tomography (PET) scanner and added PET to the imaging technologies it offers patients and physicians. The new service is managed by the nuclear medicine section in the department of radiology. Plans are being implemented now to install a cyclotron in March 2000. Prior to installation of the scanner, a radiation area survey was performed in the space being considered for the PET unit. We also needed to address other critical considerations, including the manufacturer's requirements for construction of the scanner room, special electrical needs, and how the system would connect to our existing information network. It is important to work closely with your chief financial officer and chief operations officer from the beginning of the purchasing process so that these administrators have up-to-date, supportive information about PET and the progress of the installation. We made use of a variety of promotional techniques to market the new service, including broadcast e-mail, an open house for potential referring physicians, postings on the nuclear medicine Web site and communication through the local media. We also worked with the major insurance providers that utilize our hospital to educate them about PET and its benefits. In addition, we trained our own billing staff about procedures that optimize reimbursement for PET. In March 2000, University of Kansas Hospital will install the first cyclotron in the state, enabling us to generate the drugs used for PET scanning and potentially to add targets for research PET radiopharmaceuticals. PMID:10787761
Noninvasive imaging of islet grafts using positron-emission tomography
NASA Astrophysics Data System (ADS)
Lu, Yuxin; Dang, Hoa; Middleton, Blake; Zhang, Zesong; Washburn, Lorraine; Stout, David B.; Campbell-Thompson, Martha; Atkinson, Mark A.; Phelps, Michael; Gambhir, Sanjiv Sam; Tian, Jide; Kaufman, Daniel L.
Islet transplantation offers a potential therapy to restore glucose homeostasis in type 1 diabetes patients. However, islet transplantation is not routinely successful because most islet recipients gradually lose graft function. Furthermore, serological markers of islet function are insensitive to islet loss until the latter stages of islet graft rejection. A noninvasive method of monitoring islet grafts would aid in the assessment of islet graft survival and the evaluation of interventions designed to prolong graft survival. Here, we show that recombinant adenovirus can engineer isolated islets to express a positron-emission tomography (PET) reporter gene and that these islets can be repeatedly imaged by using microPET after transplantation into mice. The magnitude of signal from engineered islets implanted into the axillary cavity was directly related to the implanted islet mass. PET signals attenuated over the following weeks because of the transient nature of adenovirus-mediated gene expression. Because the liver is the preferred site for islet implantation in humans, we also tested whether islets could be imaged after transfusion into the mouse liver. Control studies revealed that both intrahepatic islet transplantation and hyperglycemia altered the biodistribution kinetics of the PET probe systemically. Although transplanted islets were dispersed throughout the liver, clear signals from the liver region of mice receiving PET reporter-expressing islets were detectable for several weeks. Viral transduction, PET reporter expression, and repeated microPET imaging had no apparent deleterious effects on islet function after implantation. These studies lay a foundation for noninvasive quantitative assessments of islet graft survival using PET. diabetes | transplantation
Muscle use during double poling evaluated by positron emission tomography.
Bojsen-Møller, Jens; Losnegard, Thomas; Kemppainen, Jukka; Viljanen, Tapio; Kalliokoski, Kari K; Hallén, Jostein
Due to the complexity of movement in cross-country skiing (XCS), the muscle activation patterns are not well elucidated. Previous studies have applied surface electromyography (SEMG); however, recent gains in three-dimensional (3D) imaging techniques such as positron emission tomography (PET) have rendered an alternative approach to investigate muscle activation. The purpose of the present study was to examine muscle use during double poling (DP) at two work intensities by use of PET. Eight male subjects performed two 20-min DP bouts on separate days. Work intensity was ∼ 53 and 74% of peak oxygen uptake (Vo(2peak)), respectively. During exercise 188 ± 8 MBq of [(18)F]fluorodeoxyglucose ([(18)F]FDG) was injected, and subsequent to exercise a full-body PET scan was conducted. Regions of interest (ROI) were defined within 15 relevant muscles, and a glucose uptake index (GUI) was determined for all ROIs. The muscles that span the shoulder and elbow joints, the abdominal muscles, and hip flexors displayed the greatest GUI during DP. Glucose uptake did not increase significantly from low to high intensity in most upper body muscles; however, an increased GUI (P < 0.05) was seen for the knee flexor (27%) and extensor muscles (16%), and for abdominal muscles (21%). The present data confirm previous findings that muscles of the upper limb are the primary working muscles in DP. The present data further suggest that when exercise intensity increases, the muscles that span the lumbar spine, hip, and knee joints contribute increasingly. Finally, PET provides a promising alternative or supplement to existing methods to assess muscle activation in complex human movements.
Positron Emission Tomography for the Assessment of Myocardial Viability
Executive Summary In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities. After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography. A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed. The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis Magnetic Resonance Imaging for the Assessment of Myocardial Viability: An Evidence-Based Analysis Objective The objective of this analysis is to assess the
Clinical positron emission tomography/magnetic resonance imaging applications.
von Schulthess, Gustav K; Kuhn, Felix Pierre; Kaufmann, Philipp; Veit-Haibach, Patrick
Although clinical positron emission tomography (PET)/computed tomography (CT) applications were obvious and have completely replaced PET in oncology, clinical applications of PET/magnetic resonance (MR) are currently not clearly defined. This is due to the lack of clinical data, which is mainly because PET/MR technology is not clinically mature at this point. Open issues are technical and concern ease of obtaining PET attenuation correction maps, dealing with, for example, MR surface coil metal in the PET field-of-view and appropriate workflows leading to a cost-effective examination. All issues can be circumvented by using a shuttle-connected PET/CT-MR system, but the penalty is that simultaneous PET and MR imaging are not possible and potential motion between examinations may occur. Clinically, some systems installed worldwide start to have a reasonable bulk of clinical data. Preliminary results suggest that in oncology, PET/MR may have advantages over PET/CT in head and neck imaging. In liver imaging, more PET-positive lesions are seen on MR than on CT, but that does not mean that PET/MR is superior to PET/CT. Possibly in some settings where a contrast-enhanced PET/CT is needed to be diagnostic, PET/MR can be done without contrast media. Although PET/CT has virtually no role in brain imaging, this may be an important domain for PET/MR, particularly in dementia imaging. The role of PET/MR in the heart is as yet undefined, and much research will have to be done to elucidate this role. At this point, it is also not clear where the simultaneity afforded by a fully integrated PET/MR is really needed. Sequential data acquisition even on separate systems and consecutive software image fusion may well be appropriate. With the increasing installed base of systems, clinical data will be forthcoming and define more clearly where there is clinical value in PET/MR at an affordable price. PMID:23178084
Positron Emission Tomography Imaging Using Radiolabeled Inorganic Nanomaterials
Sun, Xiaolian; Cai, Weibo; Chen, Xiaoyuan
CONSPECTUS Positron emission tomography (PET) is a radionuclide imaging technology that plays an important role in preclinical and clinical research. With administration of a small amount of radiotracer, PET imaging can provide a noninvasive, highly sensitive, and quantitative readout of its organ/tissue targeting efficiency and pharmacokinetics. Various radiotracers have been designed to target specific molecular events. Compared with antibodies, proteins, peptides, and other biologically relevant molecules, nanoparticles represent a new frontier in molecular imaging probe design, enabling the attachment of different imaging modalities, targeting ligands, and therapeutic payloads in a single vector. We introduce the radiolabeled nanoparticle platforms that we and others have developed. Due to the fundamental differences in the various nanoparticles and radioisotopes, most radiolabeling methods are designed case-by-case. We focus on some general rules about selecting appropriate isotopes for given types of nanoparticles, as well as adjusting the labeling strategies according to specific applications. We classified these radiolabeling methods into four categories: (1) complexation reaction of radiometal ions with chelators via coordination chemistry; (2) direct bombardment of nanoparticles via hadronic projectiles; (3) synthesis of nanoparticles using a mixture of radioactive and nonradioactive precursors; (4) chelator-free postsynthetic radiolabeling. Method 1 is generally applicable to different nanomaterials as long as the surface chemistry is well-designed. However, the addition of chelators brings concerns of possible changes to the physicochemical properties of nanomaterials and detachment of the radiometal. Methods 2 and 3 have improved radiochemical stability. The applications are, however, limited by the possible damage to the nanocomponent caused by the proton beams (method 2) and harsh synthetic conditions (method 3). Method 4 is still in its infancy
Evaluating Positron Emission Tomography Use in Differentiated Thyroid Cancer
Esfandiari, Nazanene H.; Papaleontiou, Maria; Worden, Francis P.; Haymart, Megan R.
Background: Using the Surveillance, Epidemiology, and End Results—Medicare database, a substantial increase was found in the use of positron emission tomography (PET) scans after 2004 in differentiated thyroid cancer (DTC) patients. The reason for the increased utilization of the PET scan was not clear based on available the data. Therefore, the indications for and outcomes of PET scans performed at an academic institution were evaluated. Methods: A retrospective cohort study was performed of DTC patients who underwent surgery at the University of Michigan Health System from 2006 to 2011. After identifying patients who underwent a PET scan, indications, rate of positive PET scans, and impact on management were evaluated. For positive scans, the location of disease was characterized, and presence of disease on other imaging was determined. Results: Of the 585 patients in the cohort, 111 (19%) patients had 200 PET scans performed for evaluation of DTC. Indications for PET scan included: elevated thyroglobulin and negative radioiodine scan in 52 scans (26.0%), thyroglobulin antibodies in 13 scans (6.5%), rising thyroglobulin in 18 scans (9.0%), evaluation of abnormality on other imaging in 22 scans (11.0%), evaluation of extent of disease in 33 scans (16.5%), follow-up of previous scan in 57 scans (28.5%), other indications in two scans (1.0%), and unclear indications in three scans (1.5%). The PET scan was positive in 124 studies (62.0%); positivity was identified in the thyroid bed on 25 scans, cervical or mediastinal lymph nodes on 105 scans, lung on 28 scans, bone on four scans, and other areas on 14 scans. Therapy following PET scan was surgery in 66 cases (33.0%), chemotherapy or radiation in 23 cases (11.5%), observation in 110 cases (55.0%), and palliative care in one case (0.5%). Disease was identifiable on other imaging in 66% of cases. PET scan results changed management in 59 cases (29.5%). Conclusions: In this academic medical center, the PET scan was
Novel pulsed particle accelerator for energy dependent positron re-emission experiments.
Grill, Niklas; Piochacz, Christian; Zimnik, Samantha; Hugenschmidt, Christoph
We report on a novel device for particle acceleration based on elevation of the potential energy of beam pulses. This so-called energy elevator is particularly beneficial if both the particle source and the sample have to be near ground potential due to experimental constraints. We applied this new technique to enable depth dependent measurements of re-emitted positrons using the surface spectrometer at the NEPOMUC positron beam facility. First, a two-stage bunching system is used to generate positron pulses with a repetition rate of 5 MHz and a duration of 1.663(5) ns before their energy is raised to several keV. The whole system was shown to work with an exceptional efficiency of 88%. We demonstrated the usability of our setup by investigating the positron re-emission spectra of Ni and Pd as function of positron implantation energy. For Ni the positron work function could be determined to be ΦNi (+)=-1.4(2)eV. In addition, as predicted by theory, our experimental findings imply a positive positron work function for Pd.
Cerebrospinal fluid analysis detects cerebral amyloid-β accumulation earlier than positron emission tomography
Mattsson, Niklas
See Rabinovici (doi:10.1093/brain/aww025) for a scientific commentary on this article. Cerebral accumulation of amyloid-β is thought to be the starting mechanism in Alzheimer's disease. Amyloid-β can be detected by analysis of cerebrospinal fluid amyloid-β42 or amyloid positron emission tomography, but it is unknown if any of the methods can identify an abnormal amyloid accumulation prior to the other. Our aim was to determine whether cerebrospinal fluid amyloid-β42 change before amyloid PET during preclinical stages of Alzheimer's disease. We included 437 non-demented subjects from the prospective, longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI) study. All underwent 18F-florbetapir positron emission tomography and cerebrospinal fluid amyloid-β42 analysis at baseline and at least one additional positron emission tomography after a mean follow-up of 2.1 years (range 1.1–4.4 years). Group classifications were based on normal and abnormal cerebrospinal fluid and positron emission tomography results at baseline. We found that cases with isolated abnormal cerebrospinal fluid amyloid-β and normal positron emission tomography at baseline accumulated amyloid with a mean rate of 1.2%/year, which was similar to the rate in cases with both abnormal cerebrospinal fluid and positron emission tomography (1.2%/year, P = 0.86). The mean accumulation rate of those with isolated abnormal cerebrospinal fluid was more than three times that of those with both normal cerebrospinal fluid and positron emission tomography (0.35%/year, P = 0.018). The group differences were similar when analysing yearly change in standardized uptake value ratio of florbetapir instead of percentage change. Those with both abnormal cerebrospinal fluid and positron emission tomography deteriorated more in memory and hippocampal volume compared with the other groups (P < 0.001), indicating that they were closer to Alzheimer's disease dementia. The results were replicated after
The 511 keV emission from positron annihilation in the Galaxy
Prantzos, N.; Boehm, C.; Bykov, A. M.; Diehl, R.; Ferriere, K.; Guessoum, N.; Jean, P.; Knoedlseder, J.; Marcowith, A.; Moskalenko, I. V.; Strong, A.; Weidenspointner, G.
The first {gamma}-ray line originating from outside the Solar System that was ever detected is the 511 keV emission from positron annihilation in the Galaxy. Despite 30 years of intense theoretical and observational investigation, the main sources of positrons have not been identified up to now. Observations in the 1990s with OSSE/CGRO (Oriented Scintillation Spectrometer Experiment on GRO satellite/Compton Gamma Ray Observatory) showed that the emission is strongly concentrated toward the Galactic bulge. In the 2000s, the spectrometer SPI aboard the European Space Agency's (ESA) International Gamma Ray Astrophysics Laboratory (INTEGRAL) allowed scientists to measure that emission across the entire Galaxy, revealing that the bulge-to-disk luminosity ratio is larger than observed at any other wavelength. This mapping prompted a number of novel explanations, including rather ''exotic'' ones (e.g., dark matter annihilation). However, conventional astrophysical sources, such as type Ia supernovae, microquasars, or x-ray binaries, are still plausible candidates for a large fraction of the observed total 511 keV emission of the bulge. A closer study of the subject reveals new layers of complexity, since positrons may propagate far away from their production sites, making it difficult to infer the underlying source distribution from the observed map of 511 keV emission. However, in contrast to the rather well-understood propagation of high-energy (>GeV) particles of Galactic cosmic rays, understanding the propagation of low-energy ({approx}MeV) positrons in the turbulent, magnetized interstellar medium still remains a formidable challenge. The spectral and imaging properties of the observed 511 keV emission are reviewed and candidate positron sources and models of positron propagation in the Galaxy are critically discussed.
Distinguishing tumor recurrence from irradiation sequelae with positron emission tomography in patients treated for larynx cancer
Greven, K.M.; Williams, D.W. III; Keyes, J.W. Jr.; McGuirt, W.F.; Harkness, B.A.; Watson, N.E. Jr.; Raben, M.; Frazier, L.C.; Geisinger, K.R.; Capellari, J.O.
Distinguishing persistent or recurrent tumor from postradiation edema, or soft tissue/cartilage necrosis in patients treated for carcinoma of the larynx can be difficult. Because recurrent tumor is often submucosal, multiple deep biopsies may be necessary before a diagnosis can be established. Positron emission tomography with 18F-2-fluro-2-deoxglucose (FDG) was studied for its ability to aid in this problem. Positron emission tomography (18FDG) scans were performed on 11 patients who were suspected of having persistent or recurrent tumor after radiation treatment for carcinoma of the larynx. Patients underwent thorough history and physical examinations, scans with computerized tomography, and pathologic evaluation when indicated. Standard uptake values were used to quantitate the FDG uptake in the larynx. The time between completion of radiation treatment and positron emission tomography examination ranged from 2 to 26 months with a median of 6 months. Ten patients underwent computed tomography (CT) of the larynx, which revealed edema of the larynx (six patients), glottic mass (four patients), and cervical nodes (one patient). Positron emission tomography scans revealed increased FDG uptake in the larynx in five patients and laryngectomy confirmed the presence of carcinoma in these patients. Five patients had positron emission tomography results consistent with normal tissue changes in the larynx, and one patient had increased FDG uptake in neck nodes. This patient underwent laryngectomy, and no cancer was found in the primary site, but nodes were pathologically positive. One patient had slightly elevated FDG uptake and negative biopsy results. The remaining patients have been followed for 11 to 14 months since their positron emission studies and their examinations have remained stable. In patients without tumor, average standard uptake values of the larynx ranged from 2.4 to 4.7, and in patients with tumor, the range was 4.9 to 10.7. 18 refs., 3 figs., 1 tab.
Molecular Imaging of Transporters with Positron Emission Tomography
NASA Astrophysics Data System (ADS)
Antoni, Gunnar; Sörensen, Jens; Hall, Håkan
Positron emission tomography (PET) visualization of brain components in vivo is a rapidly growing field. Molecular imaging with PET is also increasingly used in drug development, especially for the determination of drug receptor interaction for CNS-active drugs. This gives the opportunity to relate clinical efficacy to per cent receptor occupancy of a drug on a certain targeted receptor and to relate drug pharmacokinetics in plasma to interaction with target protein. In the present review we will focus on the study of transporters, such as the monoamine transporters, the P-glycoprotein (Pgp) transporter, the vesicular monoamine transporter type 2, and the glucose transporter using PET radioligands. Neurotransmitter transporters are presynaptically located and in vivo imaging using PET can therefore be used for the determination of the density of afferent neurons. Several promising PET ligands for the noradrenaline transporter (NET) have been labeled and evaluated in vivo including in man, but a really useful PET ligand for NET still remains to be identified. The most promising tracer to date is (S,S)-[18F]FMeNER-D2. The in vivo visualization of the dopamine transporter (DAT) may give clues in the evaluation of conditions related to dopamine, such as Parkinson's disease and drug abuse. The first PET radioligands based on cocaine were not selective, but more recently several selective tracers such as [11C]PE2I have been characterized and shown to be suitable as PET radioligands. Although there are a large number of serotonin transporter inhibitors used today as SSRIs, it was not until very recently, when [11C]McN5652 was synthesized, that this transporter was studied using PET. New candidates as PET radioligands for the SERT have subsequently been developed and [11C]DASB and [11C]MADAM and their analogues are today the most promising ligands. The existing radioligands for Pgp transporters seem to be suitable tools for the study of both peripheral and central drug
Maturational changes in cerebral function in infants determined by /sup 18/FDG positron emission tomography
Chugani, H.T.; Phelps, M.E.
2-Deoxy-2(/sup 18/F)fluro-D-glucose positron emission tomography performed in human infants during development revealed progressive changes in local cerebral glucose utilization. In infants 5 weeks of age and younger, glucose utilization was highest in the sensorimotor cortex, thalamus, midbrain-brainstem, and cerebellar vermis. By 3 months, glucose metabolic activity had increased in the parietal, temporal, and occipital cortices and the basal ganglia, with subsequent increases in frontal and various association regions occurring by 8 months. These functional changes measured with positron emission tomography are in agreement with behavioral, neurophysiological, and anatomical alterations known to occur during infant development. 32 references, 2 figures, 1 table.
New techniques for positron emission tomography in the study of human neurological disorders: Progress report, December 15, 1987-June 14, 1988
Kuhl, D.E.
A brief progress report is presented describing the preparation and animal testing of /sup 11/C scopolamine and /sup 18/F fluoride. Additional studies entitled ''Automated Arterial Blood Sampling System for PET,'' Rapid Data Analysis Schemes for Functional Imaging in PET,'' and ''Tracer Kinetic Modeling in PET Measures of Cholinergic Receptors'' are described
Positron Emission Tomography for the Assessment of Myocardial Viability
Executive Summary Objective The objective was to update the 2001 systematic review conducted by the Institute For Clinical Evaluative Sciences (ICES) on the use of positron emission tomography (PET) in assessing myocardial viability. The update consisted of a review and analysis of the research evidence published since the 2001 ICES review to determine the effectiveness and cost-effectiveness of PET in detecting left ventricular (LV) viability and predicting patient outcomes after revascularization in comparison with other noninvasive techniques. Background Left Ventricular Viability Heart failure is a complex syndrome that impairs the contractile ability of the heart to maintain adequate blood circulation, resulting in poor functional capacity and increased risk of morbidity and mortality. It is the leading cause of hospitalization in elderly Canadians. In more than two-thirds of cases, heart failure is secondary to coronary heart disease. It has been shown that dysfunctional myocardium resulting from coronary heart disease (CAD) may recover contractile function (i.e. considered viable). Dysfunctional but viable myocardium may have been stunned by a brief episode of ischemia, followed by restoration of perfusion, and may regain function spontaneously. It is believed that repetitive stunning results in hibernating myocardium that will only regain contractile function upon revascularization. For people with CAD and severe LV dysfunction (left ventricular ejection fraction [LVEF] <35%) refractory to medical therapy, coronary artery bypass and heart transplantation are the only treatment options. The opportunity for a heart transplant is limited by scarcityof donor hearts. Coronary artery bypass in these patients is associated with high perioperative complications; however, there is evidence that revascularization in the presence of dysfunctional but viable myocardium is associated with survival benefits and lower rates of cardiac events. The assessment of left
77 FR 21783 - Guidance on Media Fills for Validation of Aseptic Preparations for Positron Emission Tomography...
Federal Register 2010, 2011, 2012, 2013, 2014
... the same title was announced in the Federal Register on September 30, 2011 (76 FR 60847), and Docket... HUMAN SERVICES Food and Drug Administration Guidance on Media Fills for Validation of Aseptic... guidance entitled ``Media Fills for Validation of Aseptic Preparations for Positron Emission...
76 FR 60847 - Draft Guidance on Media Fills for Validation of Aseptic Preparations for Positron Emission...
Federal Register 2010, 2011, 2012, 2013, 2014
... HUMAN SERVICES Food and Drug Administration Draft Guidance on Media Fills for Validation of Aseptic... guidance entitled ``Media Fills for Validation of Aseptic Preparations for Positron Emission Tomography... is announcing the availability of a draft guidance entitled ``Media Fills for Validation of...
Brain tumor imaging with synthesized /sup 18/F-fluorophenylalanine and positron emission tomography
Mineura, K.; Kowada, M.; Shishido, F.
Two patients with cerebral gliomas were studied with 18F-fluorophenylalanine, newly synthesized by the electrophilic substitution reaction, using positron emission tomography. The tracer accumulated markedly in the tumor lesion and delineated the extent of the lesion. This new tracer will be promising in the diagnosis of gliomas.
Detection of scalene lymph node metastases from lung cancer. Positron emission tomography.
Scott, W J; Gobar, L S; Hauser, L G; Sunderland, J J; Dewan, N A; Sugimoto, J T
Preliminary data indicate that positron emission tomography (PET) following injection of fluorodeoxyglucose F18 (FDG) is sensitive and specific for detecting malignant cells in chest tumors and mediastinal lymph nodes. We report a case of non-small cell lung cancer metastatic to clinically normal scalene lymph nodes that was correctly staged by FDG-PET. PMID:7705136
Positron Emission Tomography Methods with Potential for Increased Understanding of Mental Retardation and Developmental Disabilities
ERIC Educational Resources Information Center
Sundaram, Senthil K.; Chugani, Harry T.; Chugani, Diane C.
Positron emission tomography (PET) is a technique that enables imaging of the distribution of radiolabeled tracers designed to track biochemical and molecular processes in the body after intravenous injection or inhalation. New strategies for the use of radiolabeled tracers hold potential for imaging gene expression in the brain during development…
Attention Performance in Autism and Regional Brain Metabolic Rate Assessed by Positron Emission Tomography. Brief Report.
ERIC Educational Resources Information Center
Buchsbaum, M. S.; And Others
This evaluation of seven high functioning adults with autism utilized positron emission tomography on a visual vigilance task. Although the subjects, as a group, did as well as normal controls on the task, there was a lack of normal hemispheric asymmetry in glucose metabolic rate. A heterogeneous etiology for autism is suggested to explain…
Assessment of patient selection criteria for quantitative imaging with respiratory-gated positron emission tomography.
Bowen, Stephen R; Pierce, Larry A; Alessio, Adam M; Liu, Chi; Wollenweber, Scott D; Stearns, Charles W; Kinahan, Paul E
The objective of this investigation was to propose techniques for determining which patients are likely to benefit from quantitative respiratory-gated imaging by correlating respiratory patterns to changes in positron emission tomography (PET) metrics. Twenty-six lung and liver cancer patients underwent PET/computed tomography exams with recorded chest/abdominal displacements. Static and adaptive amplitude-gated [[Formula: see text
77 FR 8262 - Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...
Federal Register 2010, 2011, 2012, 2013, 2014
... HUMAN SERVICES Food and Drug Administration Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft...
The Neural Correlates of Driving Performance Identified Using Positron Emission Tomography
ERIC Educational Resources Information Center
Horikawa, E.; Okamura, N.; Tashiro, M.; Sakurada, Y.; Maruyama, M.; Arai, H.; Yamaguchi, K.; Sasaki, H.; Yanai, K.; Itoh, M.
Driving is a complex behavior involving multiple cognitive domains. To identify neural correlates of driving performance, [^1^5O]H"2O positron emission tomography was performed using a simulated driving task. Compared with the resting condition, simulated driving increased regional cerebral blood flow (rCBF) in the cerebellum, occipital, and…
Positron Emission Tomography in Cochlear Implant and Auditory Brainstem Implant Recipients.
ERIC Educational Resources Information Center
Miyamoto, Richard T.; Wong, Donald
Positron emission tomography imaging was used to evaluate the brain's response to auditory stimulation, including speech, in deaf adults (five with cochlear implants and one with an auditory brainstem implant). Functional speech processing was associated with activation in areas classically associated with speech processing. (Contains five…
Asymmetric 511 keV Positron Annihilation Line Emission from the Inner Galactic Disk
NASA Technical Reports Server (NTRS)
Skinner, Gerry; Weidenspointner, Georg; Jean, Pierre; Knodlseder, Jurgen; Ballmoos, Perer von; Bignami, Giovanni; Diehl, Roland; Strong, Andrew; Cordier, Bertrand; Schanne, Stephane; Winkler, Christoph
A recently reported asymmetry in the 511 keV gamma-ray line emission from the inner galactic disk is unexpected and mimics an equally unexpected one in the distribution of LMXBs seen at hard X-ray energies. A possible conclusion is that LMXBs are an important source of the positrons whose annihilation gives rise to the line. We will discuss these results, their statistical significance and that of any link between the two. The implication of any association between LMXBs and positrons for the strong annihilation radiation from the galactic bulge will be reviewed.
Three-dimensional imaging of hidden objects using positron emission backscatter
Lee, Dongwon; Cowee, Misa; Fenimore, Ed; Galassi, Mark; Looker, Quinn; Mcneil, Wendy V; Stonehill, Laura; Wallace, Mark
Positron emission backscatter imaging is a technique for interrogation and three-dimensional (3-D) reconstruction of hidden objects when we only have access to the objects from one side. Using time-of-flight differences in detected direct and backscattered positron-emitted photons, we construct 3-D images of target objects. Recently at Los Alamos National Laboratory, a fully three-dimensional imaging system has been built and the experimental results are discussed in this paper. Quantitative analysis of images reconstructed in both two- and three-dimensions are also presented.
An improved algorithm for tracking multiple, freely moving particles in a Positron Emission Particle Tracking system
NASA Astrophysics Data System (ADS)
Yang, Z.; Fryer, P. J.; Bakalis, S.; Fan, X.; Parker, D. J.; Seville, J. P. K.
Positron Emission Particle Tracking (PEPT) is a powerful technique and capable of following a single tracer accurately and non-invasively in flow and mixing processes. It has been recently extended to observe the rotation of a large particle via tracking three small positron-emitting tracers mounted, with fixed separation distances, on the surface. The Multiple-Positron Emission Particle Tracking technique has been successfully used to study the rotational and translational behaviours of a large particle in a multiphase flow; however, it was not capable of following multiple freely moving particles. This paper presents an improved Multiple-Positron Emission Particle Tracking technique that is able to track more than one particle without constraint in separation distance between the particles. It consists of an improved algorithm for location calculation, particle identification and time reconstruction. The information obtained can be used to understand the interactions and relative motions of particles with different sizes, densities and material textures in multiphase systems, and is particularly useful in pharmaceutical, chemical and metallurgical engineering studies.
Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems.
Vaquero, Juan José; Kinahan, Paul
Positron emission tomography (PET) imaging is based on detecting two time-coincident high-energy photons from the emission of a positron-emitting radioisotope. The physics of the emission, and the detection of the coincident photons, give PET imaging unique capabilities for both very high sensitivity and accurate estimation of the in vivo concentration of the radiotracer. PET imaging has been widely adopted as an important clinical modality for oncological, cardiovascular, and neurological applications. PET imaging has also become an important tool in preclinical studies, particularly for investigating murine models of disease and other small-animal models. However, there are several challenges to using PET imaging systems. These include the fundamental trade-offs between resolution and noise, the quantitative accuracy of the measurements, and integration with X-ray computed tomography and magnetic resonance imaging. In this article, we review how researchers and industry are addressing these challenges.
Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems.
Vaquero, Juan José; Kinahan, Paul
Positron emission tomography (PET) imaging is based on detecting two time-coincident high-energy photons from the emission of a positron-emitting radioisotope. The physics of the emission, and the detection of the coincident photons, give PET imaging unique capabilities for both very high sensitivity and accurate estimation of the in vivo concentration of the radiotracer. PET imaging has been widely adopted as an important clinical modality for oncological, cardiovascular, and neurological applications. PET imaging has also become an important tool in preclinical studies, particularly for investigating murine models of disease and other small-animal models. However, there are several challenges to using PET imaging systems. These include the fundamental trade-offs between resolution and noise, the quantitative accuracy of the measurements, and integration with X-ray computed tomography and magnetic resonance imaging. In this article, we review how researchers and industry are addressing these challenges. PMID:26643024
Positron Emission Tomography (PET) for Imaging Body Chemistry
Krohn, Ken
PET is a nuclear medicine technology for imaging chemical processes as they are occurring in the human body. This distinguishes it from conventional radiographic and NMR imaging, which depict anatomic changes that generally occur secondary to chemical changes. As our knowledge about human genomics and molecular biology increases and as we develop new approaches to therapy based on this biochemical information, it becomes increasingly important to be able to image important chemical processes occurring in vivo. Methods exist for imaging metabolic rates for energy utilization, cellular proliferation, and protein synthesis. The sending and receiving function of neurotransmitters can be imaged to test for mismatch in their communication function. Gene transfection can be imaged with PET reporters. All of these approaches allow the physician to better select the appropriate treatment for an individual patient, rather than basing treatment on historical experience for a population of similar patients. The technology for PET requires synthesis of positron emitting radioactive molecules, most commonly labeled with C-11 (20.4m) and F-18 (109.8 m) which are made on site with an accelerator. FNAL was involved in developing new RFQ technology for making PET isotopes. The technology also requires better imaging technology, including scintillators, and more robust algorithms for image reconstruction and data analysis.
Signal transduction images in human brain by positron emission tomography
Imahori, Y.; Fujii, R.; Ueda, S.
Analysis of changes in intracellular signal transduction will provide clear images of the projected target neurons. We have recently developed a technique which allows second-messenger imaging of changes in intracellular signal transduction which is activated in parallel with phosphoinositide (PI) turnover. Using carbon-11-labeled 1,2-diacylglycerol (DAG), we have recently succeeded in making an image of intracellular signal transduction during the course of synaptic transmission in human brains. When five healthy volunteers were examined by this technique, they had high activity in the associate field, in particular the prefrontal area. In the absence of paradigm loading, the associate field was unilaterally active, and human subjects showed predominant activity in the right prefrontal area. Activation of the ipsilateral supraorbital region and the superior temporal area was also seen at the same time. In conclusion, no previous study has directly demonstrated the unilateral predominance of the activity in the associate fields (projected target area) and the accompanying areas. Unlike the conventional positron-labeled compounds which did not permit visualization of activation of the associate fields, our technique can measure the PI turnover, as a postsynaptic response, and thus provide clear images of the projected target nerve cells in relation to higher cortical function in human brain.
Positron emission tomography detects tissue metabolic activity in myocardial segments with persistent thallium perfusion defects
Brunken, R.; Schwaiger, M.; Grover-McKay, M.; Phelps, M.E.; Tillisch, J.; Schelbert, H.R.
Positron emission tomography with /sup 13/N-ammonia and /sup 18/F-2-deoxyglucose was used to assess myocardial perfusion and glucose utilization in 51 myocardial segments with a stress thallium defect in 12 patients. Myocardial infarction was defined by a concordant reduction in segmental perfusion and glucose utilization, and myocardial ischemia was identified by preservation of glucose utilization in segments with rest hypoperfusion. Of the 51 segments studied, 36 had a fixed thallium defect, 11 had a partially reversible defect and 4 had a completely reversible defect. Only 15 (42%) of the 36 segments with a fixed defect and 4 (36%) of the 11 segments with a partially reversible defect exhibited myocardial infarction on study with positron tomography. In contrast, residual myocardial glucose utilization was identified in the majority of segments with a fixed (58%) or a partially reversible (64%) thallium defect. All of the segments with a completely reversible defect appeared normal on positron tomography. Apparent improvement in the thallium defect on delayed images did not distinguish segments with ischemia from infarction. Thus, positron emission tomography reveals evidence of persistent tissue metabolism in the majority of segments with a fixed or partially resolving stress thallium defect, implying that markers of perfusion alone may underestimate the extent of viable tissue in hypoperfused myocardial segments.
Single-photon emission computed tomography and positron-emission tomography assays for tissue oxygenation.
Chapman, J D; Schneider, R F; Urbain, J L; Hanks, G E
Radiotherapy prescription can now be customized to target the major mechanism(s) of resistance of individual tumors. In that regard, functional imaging techniques should be exploited to identify the dominant mechanism(s). Tumor biology research has identified several mechanisms of tumor resistance that may be unique to radiation treatments. These fall into 3 broad areas associated with (1) tumor hypoxic fraction, (2) tumor growth rate, (3) and the intrinsic radiosensitivity of tumor clonogens. Imaging research has markers in various stages of development for quantifying relevant information about each of these mechanisms, and those that measure tumor oxygenation and predict for radioresistance are the most advanced. Positron-emission tomography (PET) measurement of oxygen 15 has yielded important information, particularly about brain tissue perfusion, metabolism, and function. Indirect markers of tumor hypoxia have exploited the covalent binding of bioreductive intermediates of azomycin-containing compounds whose uptakes are inversely proportional to intracellular oxygen concentrations. Pilot clinical studies with single-photon emission computed tomography (SPECT) and PET detection of radiolabeled markers to tumor hypoxia have been reported. Recently, other studies have attempted to exploit the reduction properties of both technetium and copper chelates for the selective deposition of radioactive metals in hypoxic tissues. A growing number of potentially useful isotopes are now available for labeling several novel chemicals that could have the appropriate specificity and sensitivity. Preclinical studies with "microSPECT" and "microPET" will be important to define the optimal radiodiagnostic(s) for measuring tissue oxygenation and for determining the time after their administration for optimal hypoxic signal acquisition. Radiolabeled markers of growth kinetics and intrinsic radiosensitivity of cells in solid tumors are also being developed. We conclude that
ARAS: an automated radioactivity aliquoting system for dispensing solutions containing positron-emitting radioisotopes
Dooraghi, Alex A.; Carroll, Lewis; Collins, Jeffrey; van Dam, R. Michael; Chatziioannou, Arion F.
Automated protocols for measuring and dispensing solutions containing radioisotopes are essential not only for providing a safe environment for radiation workers but also to ensure accuracy of dispensed radioactivity and an efficient workflow. For this purpose, we have designed ARAS, an automated radioactivity aliquoting system for dispensing solutions containing positron-emitting radioisotopes with particular focus on fluorine-18 (18F). The key to the system is the combination of a radiation detector measuring radioactivity concentration, in line with a peristaltic pump dispensing known volumes. Results show the combined system demonstrates volume variation to be within 5 % for dispensing volumes of 20 μLmore » or greater. When considering volumes of 20 μL or greater, the delivered radioactivity is in agreement with the requested amount as measured independently with a dose calibrator to within 2 % on average. In conclusion, the integration of the detector and pump in an in-line system leads to a flexible and compact approach that can accurately dispense solutions containing radioactivity concentrations ranging from the high values typical of [18F]fluoride directly produced from a cyclotron (~0.1-1 mCi μL-1) to the low values typical of batches of [18F]fluoride-labeled radiotracers intended for preclinical mouse scans (~1-10 μCi μL-1).« less
Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography
Wolkin, A.; Jaeger, J.; Brodie, J.D.; Wolf, A.P.; Fowler, J.; Rotrosen, J.; Gomez-Mont, F.; Cancro, R.
Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities.
Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography
Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.
The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.
Pulmonary hyalinizing granuloma mimicking multiple lung metastases: report of fluorodeoxyglucose positron emission findings.
Lien, Chi-Tun; Yang, Chih-Jen; Yang, Sheau-Fang; Chou, Shah-Hwa; Huang, Ming-Shyan
Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by multiple bilateral pulmonary nodules of uncertain etiology. We describe a 71-year-old female patient with thyroid papillary carcinoma in whom bilateral pulmonary nodules were found during a routine chest radiography examination. Subsequent fluorodeoxyglucose positron emission tomography/computed tomography scan gave the impression of multiple pulmonary metastases based on high maximum standardized uptake value. She underwent video-assisted thoracoscopic surgery with wedge resection, and PHG was diagnosed on the basis of histopathologic findings. To our knowledge, this is the first report of PHG developing in a patient as a solid cancer, mimicking multiple pulmonary metastases. We also present the first description of positron emission tomography in PHG, according to a Medline search. PMID:20351580
High uptake in schneiderian papillomas of the maxillary sinus on positron-emission tomography using fluorodeoxyglucose.
Lin, F Y; Genden, E M; Lawson, W L; Som, P; Kostakoglu, L
Schneiderian papillomas are benign tumors of the nasal cavity and paranasal sinuses often asymptomatic in their early stages. We report a case of a maxillary sinus oncocytic schneiderian papilloma first detected by positron-emission tomography by using fluorodeoxyglucose (FDG). Schneiderian papillomas demonstrate increased FDG uptake, similar to that of other oncocytic tumors, making it important for otolaryngologists and radiologists to realize that high uptake of FDG does not necessarily indicate a malignant lesion. PMID:18768722
Brain dopamine metabolism in patients with Parkinson's disease measured with positron emission tomography.
Leenders, K L; Palmer, A J; Quinn, N; Clark, J C; Firnau, G; Garnett, E S; Nahmias, C; Jones, T; Marsden, C D
L-[18F] fluorodopa was administered in trace amounts intravenously to healthy control subjects and to patients with Parkinson's disease. Striatal uptake of radioactivity was measured using positron emission tomography. The capacity of the striatum to retain tracer was severely impaired in patients compared to controls. This may reflect a reduction of striatal dopamine storage in Parkinson's disease. Patients showing the "on/off" phenomenon had an even greater decrease of striatal storage capacity. Images PMID:3091770
Dynamic Positron Emission Tomography [PET] in Man Using Small Bismuth Germanate Crystals
DOE R&D Accomplishments Database
Derenzo, S. E.; Budinger, T. F.; Huesman, R. H.; Cahoon, J. L.
Primary considerations for the design of positron emission tomographs for medical studies in humans are the need for high imaging sensitivity, whole organ coverage, good spatial resolution, high maximum data rates, adequate spatial sampling with minimum mechanical motion, shielding against out of plane activity, pulse height discrimination against scattered photons, and timing discrimination against accidental coincidences. We discuss the choice of detectors, sampling motion, shielding, and electronics to meet these objectives.
Gliomatosis cerebri mimicking encephalitis evaluated using fluorine-18 fluorodeoxyglucose: Positron emission tomography/computed tomography
Kamaleshwaran, Koramadai Karuppusamy; Krishnan, Vijayan; Mohanan, Vyshakh; Shibu, Deepu; Shinto, Ajit Sugunan
Gliomatosis cerebri (GC) is a rare condition in which an infiltrative glial neoplasm spreads through the brain with preservation of the underlying structure. F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) has an important role in demonstrating the appropriate metabolism and differentiating pathologies mimicking GC on CT and magnetic resonance imaging. We describe imaging findings of FDG PET/CT in GC in a 9-year-old male child mimicking encephalitis. PMID:25589818
Gliomatosis cerebri mimicking encephalitis evaluated using fluorine-18 fluorodeoxyglucose: Positron emission tomography/computed tomography.
Kamaleshwaran, Koramadai Karuppusamy; Krishnan, Vijayan; Mohanan, Vyshakh; Shibu, Deepu; Shinto, Ajit Sugunan
Gliomatosis cerebri (GC) is a rare condition in which an infiltrative glial neoplasm spreads through the brain with preservation of the underlying structure. F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) has an important role in demonstrating the appropriate metabolism and differentiating pathologies mimicking GC on CT and magnetic resonance imaging. We describe imaging findings of FDG PET/CT in GC in a 9-year-old male child mimicking encephalitis.
Bimedial rectus hypermetabolism in convergence spasm as observed on positron emission tomography.
Jeong, Seong-Hae; Oh, Young-Mi; Kim, Chae-Yong; Kim, Ji Soo
A 52-year-old man developed vertical gaze palsy, convergence spasm, and convergence-retraction nystagmus due to glioblastoma of the right thalamus. 18F-fluorodeoxyglucose positron emission tomography (PET) inadvertently demonstrated markedly increased metabolism in the medial rectus muscles. The hypermetabolism indicates active contraction of these extraocular muscles due to excessive convergence drive attributed to inappropriate activation or disrupted inhibition of convergence neurons by the diencephalic lesion.
Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography. [Dogs
Schelbert, H.R.; Phelps, M.E.
While the results of regional myocardial glucose metabolism measurements using positron emission computed tomography (/sup 13/N-ammonia) are promising, their utility and value remains to be determined in man. If this technique can be applied to patients with acute myocardial ischemia or infarction it may permit delineation of regional myocardial segments with altered, yet still active metabolism. Further, it may become possible to evaluate the effects of interventions designed to salvage reversibly injured myocardium by this technique.
Stable confinement of positron emission tomography and magnetic resonance agents within carbon nanotubes for bimodal imaging
Cisneros, Brandon T; Law, Justin J; Matson, Michael L; Azhdarinia, Ali; Sevick-Muraca, Eva M; Wilson, Lon J
Aims Simultaneous positron emission tomography/MRI has recently been introduced to the clinic and dual positron emission tomography/MRI probes are rare and of growing interest. We have developed a strategy for producing multimodal probes based on a carbon nanotube platform without the use of chelating ligands. Materials & methods Gd3+ and 64Cu2+ ions were loaded into ultra-short single-walled carbon nanotubes by sonication. Normal, tumor-free athymic nude mice were injected intravenously with the probe and imaged over 48 h. Results & conclusion The probe was stable for up to 24 h when challenged with phosphate-buffered saline and mouse serum. Positron emission tomography imaging also confirmed the stability of the probe in vivo for up to 48 h. The probe was quickly cleared from circulation, with enhanced accumulation in the lungs. Stable encapsulation of contrast agents within ultra-short single-walled carbon nanotubes represents a new strategy for the design of advanced imaging probes with variable multimodal imaging capabilities. PMID:24628687
Positron Emission Tomography in Prostate Cancer: Summary of Systematic Reviews and Meta-Analysis
Jadvar, Hossein
Prostate cancer is a prevalent public health problem worldwide. Over the past decade, there has been tremendous research activity in the potential use of positron emission tomography with a number of radiotracers targeted to various biological aspects of this complex tumor. Systematic reviews and meta-analysis are important contributions to the relevant literature that summarize the evidence while reducing the effect of various sources of bias in the published data. The accumulation of relevant data in this clinical setting has recently provided the opportunity for systematic reviews. In this brief article, I summarize the published systematic reviews and meta-analysis of positron emission tomography in prostate cancer. Most robust evidence suggests a probable role for first-line use of positron emission tomography with radiolabeled choline in restating patients with biochemical relapse of prostate cancer with the diagnostic performance that appears to be positively associated with the serum prostate specific antigen level and velocity. Future systematic reviews will be needed for other emerging radiotracers such as those based on prostate specific membrane antigen and gastrin-releasing peptide receptor. PMID:26726317
Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia
Herhaus, Peter; Habringer, Stefan; Philipp-Abbrederis, Kathrin; Vag, Tibor; Gerngross, Carlos; Schottelius, Margret; Slotta-Huspenina, Julia; Steiger, Katja; Altmann, Torben; Weißer, Tanja; Steidle, Sabine; Schick, Markus; Jacobs, Laura; Slawska, Jolanta; Müller-Thomas, Catharina; Verbeek, Mareike; Subklewe, Marion; Peschel, Christian; Wester, Hans-Jürgen; Schwaiger, Markus; Götze, Katharina; Keller, Ulrich
Acute myeloid leukemia originates from leukemia-initiating cells that reside in the protective bone marrow niche. CXCR4/CXCL12 interaction is crucially involved in recruitment and retention of leukemia-initiating cells within this niche. Various drugs targeting this pathway have entered clinical trials. To evaluate CXCR4 imaging in acute myeloid leukemia, we first tested CXCR4 expression in patient-derived primary blasts. Flow cytometry revealed that high blast counts in patients with acute myeloid leukemia correlate with high CXCR4 expression. The wide range of CXCR4 surface expression in patients was reflected in cell lines of acute myeloid leukemia. Next, we evaluated the CXCR4-specific peptide Pentixafor by positron emission tomography imaging in mice harboring CXCR4 positive and CXCR4 negative leukemia xenografts, and in 10 patients with active disease. [68Ga]Pentixafor-positron emission tomography showed specific measurable disease in murine CXCR4 positive xenografts, but not when CXCR4 was knocked out with CRISPR/Cas9 gene editing. Five of 10 patients showed tracer uptake correlating well with leukemia infiltration assessed by magnetic resonance imaging. The mean maximal standard uptake value was significantly higher in visually CXCR4 positive patients compared to CXCR4 negative patients. In summary, in vivo molecular CXCR4 imaging by means of positron emission tomography is feasible in acute myeloid leukemia. These data provide a framework for future diagnostic and theranostic approaches targeting the CXCR4/CXCL12-defined leukemia-initiating cell niche. PMID:27175029
Aspects of positron emission tomography radiochemistry as relevant for food chemistry.
Wuest, F
Positron emission tomography (PET) is a medical imaging technique using compounds labelled with short-lived positron emitting radioisotopes to obtain functional information of physiological, biochemical and pharmacological processes in vivo. The need to understand the potential link between the ingestion of individual dietary agents and the effect of health promotion or health risk requires the exact metabolic characterization of food ingredients in vivo. This exciting but rather new research field of PET would provide new insights and perspectives on food chemistry by assessing quantitative information on pharmocokinetics and pharmacodynamics of food ingredients and dietary agents. To fully exploit PET technology in food chemistry appropriately radiolabelled compounds as relevant for food sciences are needed. The most widely used short-lived positron emitters are (11)C (t(1/2) = 20.4 min) and (18)F (t(1/2) = 109.8 min). Longer-lived radioisotopes are available by using (76)Br (t(1/2) = 16.2 h) and (124)I (t(1/2) = 4.12 d). The present review article tries to discuss some aspects for the radiolabelling of food ingredients and dietary agents either by means of isotopic labelling with (11)C or via prosthetic group labelling approaches using the positron emitting halogens (18)F, (76)Br and (124)I.
High-resolution PET (positron emission tomography) for medical science studies
Budinger, T.F.; Derenzo, S.E.; Huesman, R.H.; Jagust, W.J.; Valk, P.E. )
One of the unexpected fruits of basic physics research and the computer revolution is the noninvasive imaging power available to today's physician. Technologies that were strictly the province of research scientists only a decade or two ago now serve as the foundations for such standard diagnostic tools as x-ray computer tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), ultrasound, single photon emission computed tomography (SPECT), and positron emission tomography (PET). Furthermore, prompted by the needs of both the practicing physician and the clinical researcher, efforts to improve these technologies continue. This booklet endeavors to describe the advantages of achieving high resolution in PET imaging. 6 refs., 21 figs.
High-resolution PET [Positron Emission Tomography] for Medical Science Studies
DOE R&D Accomplishments Database
Budinger, T. F.; Derenzo, S. E.; Huesman, R. H.; Jagust, W. J.; Valk, P. E.
One of the unexpected fruits of basic physics research and the computer revolution is the noninvasive imaging power available to today's physician. Technologies that were strictly the province of research scientists only a decade or two ago now serve as the foundations for such standard diagnostic tools as x-ray computer tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), ultrasound, single photon emission computed tomography (SPECT), and positron emission tomography (PET). Furthermore, prompted by the needs of both the practicing physician and the clinical researcher, efforts to improve these technologies continue. This booklet endeavors to describe the advantages of achieving high resolution in PET imaging.
Brain energy metabolism and dopaminergic function in Huntington's disease measured in vivo using positron emission tomography
Leenders, K.L.; Frackowiak, R.S.; Quinn, N.; Marsden, C.D.
A 48-year-old man with typical Huntington's disease was investigated with computed tomography (CT) and positron emission tomography. Regional cerebral blood flow, oxygen extraction, oxygen and glucose utilization, L-Dopa uptake, and dopamine (D2) receptor binding were measured using several positron-labelled tracers. CT showed slight atrophy of the head of caudate but no cortical atrophy, although distinct frontal lobe dysfunction was present on psychometric testing. Oxygen and glucose metabolism and cerebral blood flow were decreased in the striata and to a lesser extent in frontal cortex. Cerebral blood flow was in the low normal range throughout the remainder of the brain. A normal metabolic ratio was found in all regions, since the changes in glucose utilization paralleled those in oxygen consumption. The capacity of the striatum to store dopamine as assessed by L-( YF)-fluorodopa uptake was normal, but dopamine (D2) receptor binding was decreased when compared to normal subjects.
Enhancement of molecular sensitivity in positron emission tomography with quantum correlation of γ-ray photons
Sato, K.; Kobayashi, Y.
Enhancement of molecular sensitivity in positron emission tomography (PET) has long been discussed with respect to imaging instrumentation and algorithms for data treatment. Here, the molecular sensitivity in PET is discussed on the basis of 2-dimensional coincident measurements of 511 keV γ ray photons resultant from two-photon annihilation. Introduction of an additional selection window based on the energy sum and difference of the coincidently measured γ ray photons, without any significant instrumental and algorithmic changes, showed an improvement in the signal-to-noise ratio (SNR) by an order of magnitude. Improvement of performance characteristics in the PET imaging system was demonstrated by an increase in the noise equivalent count rate (NECR) which takes both the SNR and the detection efficiency into consideration. A further improvement of both the SNR and the NECR is expected for the present system in real clinical and in-vivo environments, where much stronger positron sources are employed.
Enhancement of molecular sensitivity in positron emission tomography with quantum correlation of γ-ray photons.
Sato, K; Kobayashi, Y
Enhancement of molecular sensitivity in positron emission tomography (PET) has long been discussed with respect to imaging instrumentation and algorithms for data treatment. Here, the molecular sensitivity in PET is discussed on the basis of 2-dimensional coincident measurements of 511 keV γ ray photons resultant from two-photon annihilation. Introduction of an additional selection window based on the energy sum and difference of the coincidently measured γ ray photons, without any significant instrumental and algorithmic changes, showed an improvement in the signal-to-noise ratio (SNR) by an order of magnitude. Improvement of performance characteristics in the PET imaging system was demonstrated by an increase in the noise equivalent count rate (NECR) which takes both the SNR and the detection efficiency into consideration. A further improvement of both the SNR and the NECR is expected for the present system in real clinical and in-vivo environments, where much stronger positron sources are employed.
Proton therapy is a treatment modality of increasing utility in clinical radiation oncology mostly because its dose distribution conforms more tightly to the target volume than x-ray radiation therapy. One important feature of proton therapy is that it produces a small amount of positron-emitting isotopes along the beam-path through the non-elastic nuclear interaction of protons with target nuclei such as {sup 12}C, {sup 14}N, and {sup 16}O. These radioisotopes, mainly {sup 11}C, {sup 13}N and {sup 15}O, allow imaging the therapy dose distribution using positron emission tomography (PET). The resulting PET images provide a powerful tool for quality assurance of the treatment, especially when treating inhomogeneous organs such as the lungs or the head-and-neck, where the calculation of the dose distribution for treatment planning is more difficult. This paper uses Monte Carlo simulations to predict the yield of positron emitters produced by a 250 MeV proton beam, and to simulate the productions of the image in a clinical PET scanner.
Positron emission tomographic imaging of tumors using monoclonal antibodies. Progress report, April 15, 1992--October 31, 1992
Zalutsky, M.R.
This research project is developing methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). This report describes the development of methods for labeling MAbs and their fragments with positron-emitting halogen nuclides, fluorine-18 and iodine-124. These nulides were selected because of the widespread availability of F-18 and because of our extensive experience in the development of new protein radiohalogenation methods.
Distributed microprocessor automation network for synthesizing radiotracers used in positron emission tomography
Russell, J.A.G.; Alexoff, D.L.; Wolf, A.P.
This presentation describes an evolving distributed microprocessor network for automating the routine production synthesis of radiotracers used in Positron Emission Tomography. We first present a brief overview of the PET method for measuring biological function, and then outline the general procedure for producing a radiotracer. The paper identifies several reasons for our automating the syntheses of these compounds. There is a description of the distributed microprocessor network architecture chosen and the rationale for that choice. Finally, we speculate about how this network may be exploited to extend the power of the PET method from the large university or National Laboratory to the biomedical research and clinical community at large. 20 refs. (DT)
Treatment modification of yttrium-90 radioembolization based on quantitative positron emission tomography/CT imaging.
Chang, Ted T; Bourgeois, Austin C; Balius, Anastasia M; Pasciak, Alexander S
Treatment activity for yttrium-90 ((90)Y) radioembolization when calculated by using the manufacturer-recommended technique is only partially patient-specific and may result in a subtumoricidal dose in some patients. The authors describe the use of quantitative (90)Y positron emission tomography/computed tomography as a tool to provide patient-specific optimization of treatment activity and evaluate this new method in a patient who previously received traditional (90)Y radioembolization. The modified treatment resulted in a 40-Gy increase in absorbed dose to tumor and complete resolution of disease in the treated area within 3 months.
Clinical correlates of decreased anteroposterior metabolic gradients in positron emission tomography (PET) of schizophrenic patients
DeLisi, L.E.; Buchsbaum, M.S.; Holcomb, H.H.; Dowling-Zimmerman, S.; Pickar, D.; Boronow, J.; Morihisa, J.M.; van Kammen, D.P.; Carpenter, W.; Kessler, R.
The finding in schizophrenic patients of a reversal of the normal frontal to posterior pattern of brain metabolic activity with positron emission tomography (PET) is of interest, but its relevance to psychopathology is unknown. Using PET, the authors studied 21 patients with chronic schizophrenia and 21 age- and sex-matched control subjects. Although eight of the 21 patients and only one of the control subjects showed a relatively lower anteroposterior metabolic gradient, no clinical correlates of this finding were noted. In addition, cerebral atrophy, as determined by CAT scan, was not associated with this aberrant metabolic pattern.
Radiolabeled Phosphonium Salts as Mitochondrial Voltage Sensors for Positron Emission Tomography Myocardial Imaging Agents.
Kim, Dong-Yeon; Min, Jung-Joon
Despite substantial advances in the diagnosis of cardiovascular disease, (18)F-labeled positron emission tomography (PET) radiopharmaceuticals remain necessary to diagnose heart disease because clinical use of current PET tracers is limited by their short half-life. Lipophilic cations such as phosphonium salts penetrate the mitochondrial membranes and accumulate in mitochondria of cardiomyocytes in response to negative inner-transmembrane potentials. Radiolabeled tetraphenylphosphonium cation derivatives have been developed as myocardial imaging agents for PET. In this review, a general overview of these radiotracers, including their radiosynthesis, in vivo characterization, and evaluation is provided and clinical perspectives are discussed. PMID:27540422
Distributed Microprocessor Automation Network for Synthesizing Radiotracers Used in Positron Emission Tomography [PET
DOE R&D Accomplishments Database
Russell, J. A. G.; Alexoff, D. L.; Wolf, A. P.
This presentation describes an evolving distributed microprocessor network for automating the routine production synthesis of radiotracers used in Positron Emission Tomography. We first present a brief overview of the PET method for measuring biological function, and then outline the general procedure for producing a radiotracer. The paper identifies several reasons for our automating the syntheses of these compounds. There is a description of the distributed microprocessor network architecture chosen and the rationale for that choice. Finally, we speculate about how this network may be exploited to extend the power of the PET method from the large university or National Laboratory to the biomedical research and clinical community at large. (DT)
Using Positron Emission Tomography to Study Transporter-Mediated Drug–Drug Interactions in Tissues
Wulkersdorfer, B; Wanek, T; Bauer, M; Zeitlinger, M; Müller, M; Langer, O
Drug disposition is highly regulated by membrane transporters. Some transporter-mediated drug–drug interactions (DDIs) may not manifest themselves in changes in systemic exposure but rather in changes in tissue exposure of drugs. To better assess the impact of transporter-mediated DDIs in tissues, positron emission tomography (PET)—a noninvasive imaging method—plays an increasingly important role. In this article, we provide examples of how PET can be used to assess transporter-mediated DDIs in different organs. PMID:24682030
Positron Emission Tomography-Scanner at Children`s Hospital of Michigan at Detroit, Michigan
Not Available
The Department of Energy has prepared an environmental assessment (EA), DOE/EA-0795, to support the DOE decision to provide a grant of $7,953,600 to be used in support of a proposed Positron Emission Tomography Scanner at Children`s Hospital of Michigan at Detroit, Michigan. Based upon the analysis in the EA, DOE has determined that the proposed action is not a major Federal action significantly affected the quality of the human environment within the meaning of the National Environmental Policy Act of 1969 (NEPA). Therefore, the preparation of an Environmental Impact Statement is not required and DOE is issuing this Finding of No Significant Impact (FONSI).
Florbetapir (18F) for brain amyloid positron emission tomography: highlights on the European marketing approval.
Cortes-Blanco, Anabel; Prieto-Yerro, Concha; Martinez-Lazaro, Raul; Zamora, Javier; Jiménez-Huete, Adolfo; Haberkamp, Marion; Pohly, Johannes; Enzmann, Harald; Zinserling, Jörg; Strassmann, Valerie; Broich, Karl
Florbetapir (18F) for brain amyloid positron emission tomography (PET) imaging has been recently approved in Europe to estimate β-amyloid neuritic plaque density in the brain when the subject is still alive. Such density is one of the key issues for the definitive diagnosis of Alzheimer's disease (AD) at autopsy. This capability of florbetapir (18F) is regarded as a significant improvement in the diagnostic procedures for adult patients with cognitive impairment who are being evaluated for AD and other causes of cognitive impairment. The current paper highlights the specific characteristics of the European marketing authorization of florbetapir (18F).
Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings.
Tulving, E; Kapur, S; Craik, F I; Moscovitch, M; Houle, S
Data are reviewed from positron emission tomography studies of encoding and retrieval processes in episodic memory. These data suggest a hemispheric encoding/retrieval asymmetry model of prefrontal involvement in encoding and retrieval of episodic memory. According to this model, the left and right prefrontal lobes are part of an extensive neuronal network that subserves episodic remembering, but the two prefrontal hemispheres play different roles. Left prefrontal cortical regions are differentially more involved in retrieval of information from semantic memory and in simultaneously encoding novel aspects of the retrieved information into episodic memory. Right prefrontal cortical regions, on the other hand, are differentially more involved in episodic memory retrieval. PMID:8134342
In vivo measurement of regional cerebral haematocrit using positron emission tomography
Lammertsma, A.A.; Brooks, D.J.; Beaney, R.P.; Turton, D.R.; Kensett, M.J.; Heather, J.D.; Marshall, J.; Jones, T.
A method is described for measuring the regional cerebral-to-large vessel haematocrit ratio using inhalation of carbon-11-labelled carbon monoxide and the intravenous injection of carbon-11-labelled methyl-albumin in combination with positron emission tomography. The mean value in a series of nine subjects was 0.69. This is approximately 20% lower than the value of 0.85 previously reported. It is concluded that previous measurements of regional cerebral blood volume using a haematocrit ratio of 0.85 will have underestimated the value of regional cerebral blood volume by 20%.
Positron emission tracking of individual particles in particle-laden rimming flow
NASA Astrophysics Data System (ADS)
Denissenko, P.; Guyez, E.; Thomas, P. J.; Parker, D. J.; Seville, J. P. K.
The motion of a single tracer particle in particle-laden rimming flows is investigated experimentally by means of Positron Emission Particle Tracking (PEPT). Semi-dilute suspensions, with a volume fraction of 8% of heavy particles are considered. The trajectory of the tracer particle is monitored for several thousand cylinder revolutions and related to the optically recorded drift of the large-scale granular segregation bands developing in the cylinder. Results of the data analysis provide first insights into the relation between behaviour of individual particles and the spatiotemporal dynamics displayed by the macroscopic particle-segregation patterns.
An advanced fully 3D OSEM reconstruction for positron emission tomography
NASA Astrophysics Data System (ADS)
Yun, Ming-Kai; Liu, Shuang-Quan; Shan, Bao-Gi; Wei, Long
A fully 3D OSEM reconstruction method for positron emission tomography (PET) based on symmetries and sparse matrix technique is described. Great savings in both storage space and computation time were achieved by exploiting the symmetries of scanner and sparseness of the system matrix. More reduction of storage requirement was obtained by introducing the approximation of system matrix. Iteration-filter was performed to restrict image noise in reconstruction. Performances of simulation data and phantom data got from Micro-PET (Type: Epuls-166) demonstrated that similar image quality was achieved using the approximation of the system matrix.
Clinical and research applications of simultaneous positron emission tomography and MRI
Fraioli, F
Abstract Evaluation of the molecular processes responsible for disease pathogenesis and progression represents the new frontier of clinical radiology. Multimodality imaging lies at the cutting edge, combining the power of MRI for tissue characterization, microstructural appraisal and functional assessment together with new positron emission tomography (PET) tracers designed to target specific metabolic processes. The recent commercial availability of an integrated clinical whole-body PET-MRI provides a hybrid platform for exploring and exploiting the synergies of multimodal imaging. First experiences on the clinical and research application of hybrid PET-MRI are emerging. This article reviews the rapidly evolving field and speculates on the potential future direction. PMID:24234585
[Positron emission tomography/computed tomography in follow-up programmes for patients with colorectal cancer].
Hansen, Anne Fogh; Jensen, Mads Radmer; Nordholm-Carstensen, Andreas
The current follow-up programmes for patients with colorectal cancer (CRC) after curative surgery do not include 18F-fluorodeoxyglucose-positron emission tomography (PET). Several small studies on selected patient populations indicate a high sensitivity of PET/computed tomography (CT) on visualizing relapse in patients with CRC after curative surgery. Therefore, PET/CT could probably be valuable in patients with unexplained increase in carcinoembryonic antigen level or a clinical suspicion of relapse, but PET/CT is not recommended as a standard in follow-up after CRC. PMID:27649583
Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning
Takahashi, Hirohide; Snow, B.J.; Bhatt, M.H.; Peppard, R.; Eisen, A.; Calne, D.B. )
Although rare, the chronic neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and idiopathic parkinsonism coexist to a greater degree than expected by chance. This suggests that patients with ALS may have subclinical lesions of the nigrostriatal dopaminergic pathway. To study this hypothesis, the authors did positron emission tomography with 6-fluorodopa on 16 patients with sporadic ALS and without extrapyramidal disease, and compared the results with age-matched controls. They found a significant progressive fall in 6-fluorodopa uptake with time since diagnosis, and reduced dopaminergic function in 3 patients with ALS of long duration. This supports the hypothesis that ALS and IP may share pathogenesis, and, perhaps, etiology.
Count rate capability considerations and results for a positron emission tomograph
Yamamoto, S.; Amano, M.; Hirose, Y.; Iida, H.; Miura, S.; Kanno, I.
Count rate capability is an important characteristic for quantitative measurements in positron emission tomography (PET), especially for fast dynamic studies. Insufficient count rate capability reduces effective sensitivity and counting statistics of images at high count rate as well as quantification. Count rate capability is affected by many factors. The factors are categorized as follows: (1) factor of object size to be scanned, (2) factor of geometrical design of PET, (3) factor on electronics of PET. The purpose of this paper is to evaluate system count rate capabilities by changing these factors, and to estimate dominant ones.
Sensitivity estimation in time-of-flight list-mode positron emission tomography
Herraiz, J. L.; Sitek, A.
Purpose: An accurate quantification of the images in positron emission tomography (PET) requires knowing the actual sensitivity at each voxel, which represents the probability that a positron emitted in that voxel is finally detected as a coincidence of two gamma rays in a pair of detectors in the PET scanner. This sensitivity depends on the characteristics of the acquisition, as it is affected by the attenuation of the annihilation gamma rays in the body, and possible variations of the sensitivity of the scanner detectors. In this work, the authors propose a new approach to handle time-of-flight (TOF) list-mode PET data, which allows performing either or both, a self-attenuation correction, and self-normalization correction based on emission data only. Methods: The authors derive the theory using a fully Bayesian statistical model of complete data. The authors perform an initial evaluation of algorithms derived from that theory and proposed in this work using numerical 2D list-mode simulations with different TOF resolutions and total number of detected coincidences. Effects of randoms and scatter are not simulated. Results: The authors found that proposed algorithms successfully correct for unknown attenuation and scanner normalization for simulated 2D list-mode TOF-PET data. Conclusions: A new method is presented that can be used for corrections for attenuation and normalization (sensitivity) using TOF list-mode data.
Clinical evaluation of a high-resolution (2. 6-mm) positron emission tomography
Valk, P.E.; Jagust, W.J.; Derenzo, S.E.; Huesman, R.H.; Geyer, A.B.; Budinger, T.F. )
The intrinsic resolution of the Donner 600-crystal positron emission tomograph (PET 600) is 2.6 mm full width at half maximum (FWHM) in-plane and 6 mm FWHM axially. More than 100 patients with glioma, radiation necrosis, Alzheimer disease, or epilepsy have been studied with this system. Approximately 1 million events are acquired in 15 minutes, starting 1 hour after injection of 10 mCi (370 MBq) of fluorine-18-fluorodeoxyglucose. Normal structures as small as the superior colliculi and the external capsule have been resolved. Improved separation of the cortical ribbon from adjacent white matter has allowed more accurate determination of cortical metabolic rate. In two of 15 patients undergoing evaluation for recurrent glioma, the PET 600 images showed tumor uptake that was not apparent on a lower-resolution study. A high-activity orbiting transmission source with electronic collimation allows accurate, short-duration transmission measurements to be made after radiopharmaceutical administration. The anatomic detail seen on the transmission images can be used for reproducible patient positioning with an accuracy of 1-2 mm perpendicular to the image plane. These findings demonstrate the practicality and clinical effectiveness of high-resolution positron emission tomography.
Positron emission tomography for measurement of copper fluxes in live organisms.
Peng, Fangyu
Copper is an essential nutrient for the physiology of live organisms, but excessive copper can be harmful. Copper radioisotopes are used for measurement of copper fluxes in live organisms using a radioactivity assay of body fluids or whole-body positron emission tomography (PET). Hybrid positron emission tomography-computed tomography (PET/CT) is a versatile tool for real-time measurement of copper fluxes combining the high sensitivity and quantification capability of PET and the superior spatial resolution of CT for anatomic localization of radioactive tracer activity. Kinetic analysis of copper metabolism in the liver and extrahepatic tissues of Atp7b(-/-) knockout mice, a mouse model of Wilson's disease, demonstrated the feasibility of measuring copper fluxes in live organisms with PET/CT using copper-64 chloride ((64) CuCl2 ) as a radioactive tracer ((64) CuCl2 -PET/CT). (64) CuCl2 -PET/CT holds potential as a useful tool for the diagnosis of inherited and acquired human copper metabolism disorders and for monitoring the effects of copper-modulating therapy.
Clinical experience with the first combined positron emission tomography/computed tomography scanner in Australia.
Lau, W F Eddie; Binns, David S; Ware, Robert E; Ramdave, Shakher; Cachin, Florent; Pitman, Alexander G; Hicks, Rodney J
Metabolic imaging with fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is increasing rapidly worldwide because of superior accuracy compared with conventional non-invasive techniques used for evaluating cancer. Limited anatomical information from FDG-PET images alone dictates that complementary use with structural imaging is required to optimise benefit. Recently, combined positron emission tomography/computed tomography (PET/CT) scanners have overtaken standalone PET scanners as the most commonly purchased PET devices. We describe our experience of over 5500 scans performed since the first PET/CT scanner in Australia was commissioned at the Peter MacCallum Cancer Centre (PMCC), Melbourne, in January 2002. Clinical indications for PET/CT scans performed at PMCC largely reflect current Medicare reimbursement policy. Advantages of PET/CT include greater patient comfort and higher throughput, greater diagnostic certainty and accuracy, improved biopsy methods, and better treatment planning. We believe PET/CT will underpin more effective and efficient imaging paradigms for many common tumours, and lead to a decrease in imaging costs. PMID:15720173
Catecholamine stimulation, substrate competition, and myocardial glucose uptake in conscious dogs assessed with positron emission tomography.
Merhige, M E; Ekas, R; Mossberg, K; Taegtmeyer, H; Gould, K L
Uptake of radiolabelled deoxyglucose out of proportion to reduced coronary flow demonstrated by positron emission tomography has been used to identify reversibly ischemic, viable myocardium. For this concept to be applied reliably in the clinical setting, factors that may depress glucose availability independent of tissue viability, such as adrenergic stimulation and substrate competition, must be examined. Accordingly, we studied the effect of catecholamine stimulation by dopamine on myocardial glucose uptake in vivo using chronically instrumented, intact dogs and positron emission tomography. We measured myocardial activity of [2-18F]-2-deoxyglucose (FDG) and 82Rb in glucose-loaded animals randomly studied during dopamine infusion, during insulin infusion, and then during their combined infusion. Myocardial FDG uptake was significantly decreased when animals were treated with dopamine, compared with treatment in the same animals with insulin. When insulin was added to the dopamine infusion, myocardial FDG uptake was restored. In contrast, myocardial activity of 82Rb, which is taken up in proportion to coronary flow, was similar under all three experimental conditions. Plasma glucose, free fatty acid, and lactate concentrations were determined before and during each infusion. The depression of myocardial FDG activity seen during dopamine infusion and its reversal with addition of insulin can be explained on the basis of effects of these hormones on substrate availability and competition.
Cerebral blood volume measured with inhaled C/sup 15/O and positron emission tomography
Martin, W.R.; Powers, W.J.; Raichle, M.E.
Local cerebral blood volume (CBV) has been measured previously with inhaled /sup 11/CO and positron emission tomography (PET). The model used assumes that equilibrium in tracer concentration has occurred between arterial and systemic venous blood before the PET measurement is made. To verify that this model may be used with the much shorter half-lived C/sup 15/O, we have simultaneously measured arterial and venous blood radioactivity following C/sup 15/O inhalation. Equilibrium occurred 95 +/- 39 s after inhalation (n = 7). If the PET measurement is commenced prior to arteriovenous equilibrium, significant errors occur in calculated CBV. These data indicate that C/sup 15/O may be used as a tracer for CBV measurement provided that emission data collection commences at approximately 120 s after inhalation. Strict quality control measures must be maintained to minimize the contamination of administered C/sup 15/O with /sup 15/O-labeled CO/sub 2/.
18F-fluorodeoxyglucose positron emission tomography imaging in brain tumours: the Western Australia positron emission tomography/cyclotron service experience.
McCarthy, M; Yuan, J B; Campbell, A; Lenzo, N P; Butler-Henderson, K
(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans in the first 49 patients referred with either possible brain tumour or brain tumour recurrence were reviewed. FDG-PET imaging was reported with reference to anatomical imaging. Based on the report the FDG study was classified as either positive or negative for the presence of tumour. Thirty-eight cases were included in the analysis, 21 having pathological data and 17 with diagnostic clinical follow up. Eleven were excluded, as they had inadequate follow-up data. Of the 21 cases with pathology, 18 were shown to have tumour. In this group there were five false-negative scans and two false-positive PET scans. Seventeen cases were assessed by clinical follow up, nine were considered to have been tumour. There were two false negatives with one false positive. The overall sensitivity, specificity and positive and negative predictive values were 74, 73, 87 and 53% respectively. This is similar to figures previously quoted in published work. Despite relatively limited numbers, the utility of FDG PET imaging in our hands is similar to published reports. With a positive predictive value of 87%, a positive FDG study indicates a high likelihood that there is brain tumour present. A negative study does not exclude the presence of tumour.
Positron emission tomography in the quantification of cellular and biochemical responses to intrapulmonary particulates
Jones, Hazel A. . E-mail: firstname.lastname@example.com; Hamacher, Kurt; Clark, John C.; Schofield, John B.; Krausz, Thomas; Haslett, Christopher; Boobis, Alan R.
Inhaled mineral dusts and fibres can cause chronic pulmonary inflammation, often leading to permanent scarring with loss of function, but the mechanisms involved remain obscure. There are currently no good methods for monitoring inflammatory processes in situ. Positron emission tomography (PET) of suitable intravenously injected radiolabelled markers provides non-invasive and repeatable methods of quantifying biochemical and cellular responses. We have developed animal models of fibrotic and non-fibrotic pulmonary response to particulate instillation and characterised these by histology. Different components of the inflammatory response have been investigated by PET: (1) [{sup 18}F]-labelled fluoro-deoxyglucose, a positron emitting glucose analogue, accumulates in cells in proportion to their glucose uptake; ex vivo microautoradiography indicates that neutrophils are the cells responsible for an increased signal during pulmonary inflammation; a persistently high uptake is associated with lung scarring. (2) The radioligand [{sup 11}C]-R-PK11195 binds to benzodiazepine-like receptors abundant in macrophages; following particulate instillation, the [{sup 11}C]-R-PK11195 PET signal tracks with lung macrophage accumulation and also localises to regions consistent with macrophage clearance; poor macrophage clearance is associated with fibrosis. (3) [{sup 18}F]-fluoroproline is likely a substrate for extracellular matrix production, especially proline-rich collagen; during active scarring, the rate of lung uptake of fluoroproline is elevated. Localisation of radioactivity in the lung has been validated ex vivo by microautoradiography of tritium analogues of each of the positron emitting tracers. The use of PET to monitor different inflammatory processes by repeated scanning of the same animal or individual is helping to identify key events in the fibrotic process.
Measurement of human cerebral blood flow with (15O)butanol and positron emission tomography
Berridge, M.S.; Adler, L.P.; Nelson, A.D.; Cassidy, E.H.; Muzic, R.F.; Bednarczyk, E.M.; Miraldi, F. )
Although H2(15)O is widely used for CBF measurement by positron tomography, it underestimates CBF, especially at elevated flow rates. Several tracers, including butanol, overcome this problem, but the short half-life of 15O provides advantages that cause water to remain the tracer of choice. The authors report the first use and evaluation of 15O-labeled butanol for CBF measurement. Flow measurements made in a similar fashion with water and butanol at 10-min intervals were compared in normal volunteers under resting and hypercapnic conditions. Regional analysis showed good agreement between the tracers at low flows, and significant underestimation of flow by water relative to butanol in regions of elevated flow. The observed relationship between the tracers and the curve-fitted permeability-surface area product for water (133 ml.100 g-1.min-1) follow the known relationship between water and true flow. These observations indicate that (15O)-butanol provided accurate measurements of human regional CBF under conditions of elevated perfusion. They conclude that butanol is a convenient and accurate method for routine CBF determination by positron emission tomography.
Cosmic ray electrons, positrons and the synchrotron emission of the Galaxy: consistent analysis and implications
Bernardo, Giuseppe Di; Evoli, Carmelo; Gaggero, Daniele; Grasso, Dario; Maccione, Luca E-mail: firstname.lastname@example.com E-mail: firstname.lastname@example.com
A multichannel analysis of cosmic ray electron and positron spectra and of the diffuse synchrotron emission of the Galaxy is performed by using the DRAGON code. This study is aimed at probing the interstellar electron source spectrum down to E ∼< 1GeV and at constraining several propagation parameters. We find that above 4GeV the e{sup −} source spectrum is compatible with a power-law of index ∼ 2.5. Below 4GeV instead it must be significantly suppressed and the total lepton spectrum is dominated by secondary particles. The positron spectrum and fraction measured below a few GeV are consistently reproduced only within low reacceleration models. We also constrain the scale-height z{sub t} of the cosmic-ray distribution using three independent (and, in two cases, original) arguments, showing that values of z{sub t} ∼< 2kpc are excluded. This result may have strong implications for particle dark matter searches.
Development of a treatment planning system for BNCT based on positron emission tomography data: preliminary results
NASA Astrophysics Data System (ADS)
Cerullo, N.; Daquino, G. G.; Muzi, L.; Esposito, J.
Present standard treatment planning (TP) for glioblastoma multiforme (GBM - a kind of brain tumor), used in all boron neutron capture therapy (BNCT) trials, requires the construction (based on CT and/or MRI images) of a 3D model of the patient head, in which several regions, corresponding to different anatomical structures, are identified. The model is then employed by a computer code to simulate radiation transport in human tissues. The assumption is always made that considering a single value of boron concentration for each specific region will not lead to significant errors in dose computation. The concentration values are estimated "indirectly", on the basis of previous experience and blood sample analysis. This paper describes an original approach, with the introduction of data on the in vivo boron distribution, acquired by a positron emission tomography (PET) scan after labeling the BPA (borono-phenylalanine) with the positron emitter 18F. The feasibility of this approach was first tested with good results using the code CARONTE. Now a complete TPS is under development. The main features of the first version of this code are described and the results of a preliminary study are presented. Significant differences in dose computation arise when the two different approaches ("standard" and "PET-based") are applied to the TP of the same GBM case.
Positron Emission Tomography Imaging of Cancer Biology: Current Status and Future Prospects
Chen, Kai; Chen, Xiaoyuan
Positron emission tomography (PET) is one of the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. The principal goal of PET imaging is to visualize, characterize, and measure biological processes at the cellular, subcellular, and molecular levels in living subjects using noninvasive procedures. PET imaging takes advantage of the traditional diagnostic imaging techniques and introduces positron-emitting probes to determine the expression of indicative molecular targets at different stages of cancer progression. Although [18F]fluorodeoxyglucose ([18F]FDG)-PET has been widely utilized for staging and restaging of cancer, evaluation of response to treatment, differentiation of post-therapy alterations from residual or recurrent tumor, and assessment of prognosis, [18F]FDG is not a target-specific PET tracer. Over the last decade, numerous target-specific PET tracers have been developed and evaluated in preclinical and clinical studies. This review provides an overview of the current status and trends in the development of non-[18F]FDG PET probes in oncology and their application in the investigation of cancer biology. PMID:21362517
The Use and Misuse of Positron Emission Tomography in Lung Cancer Evaluation
Chang, Ching-Fei; Rashtian, Afshin; Gould, Michael K.
Synopsis Positron emission tomography (PET) has been studied for a variety of indications in patients with known or suspected non-small cell lung cancer (NSCLC). In this review, we discuss the potential benefits and limitations of PET for characterizing lung nodules, staging the mediastinum, identifying occult distant metastasis, determining prognosis and treatment response, guiding plans for radiation therapy, restaging during and after treatment, and selecting targets for tissue sampling. (Table 1) Evidence from randomized, controlled trials supports the use of PET for initial staging in NSCLC, while lower quality evidence from studies of diagnostic accuracy and modeling studies supports the use of PET for characterizing lung nodules. For most other indications in NSCLC, additional studies are required to clarify the role of PET and determine who is most likely to benefit. PMID:22054883
The Australian government's review of positron emission tomography: evidence-based policy-making in action.
Ware, Robert E; Francis, Hilton W; Read, Kenneth E
The Commonwealth Government constituted the Medicare Services Advisory Committee (MSAC) to implement its commitment to entrench the principles of evidence-based medicine in Australian clinical practice. With its recent review of positron emission tomography (PETReview), the Commonwealth intervened in an established MSAC process, and sanctioned the stated objective to restrict expenditure on the technology. In our opinion: The evaluation of evidence by PETReview was fundamentally compromised by a failure to meet the terms of reference, poor science, poor process and unique decision-making benchmarks. By accepting the recommendations of PETReview, the Commonwealth is propagating information which is not of the highest quality. The use of inferior-quality information for decision-making by doctors, patients and policy-makers is likely to harm rather than enhance healthcare outcomes. PMID:15200360
Extramedullary Plasmacytoma of the Gallbladder Detected on Fluorine 18-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Fakhri, Asif Ali; Rodrigue, Paul David; Fakhri, Amena Fatima
Extramedullary plasmacytoma is rare in patients with diagnosed multiple myeloma. Soft tissue plasmacytoma of the gallbladder is particularly uncommon and has been described in only a handful of cases. Diagnosis of gallbladder plasmacytoma with fluorine 18-fluorodeoxyglucose (F18-FDG) positron emission tomography/computed tomography (PET/CT) has not previously been reported. We present a 65-year-old female with a history of multiple myeloma who underwent a restaging F18-FDG-PET/CT which showed a focal area of hypermetabolic activity, corresponding to a nodular lesion within the posterior gallbladder wall. The patient underwent successful cholecystectomy, with surgical pathology revealing gallbladder plasmacytoma. A follow-up scan was negative for active malignancy. This is a novel case of gallbladder plasmacytoma diagnosed on whole-body F18-FDG PET/CT – thus demonstrating the clinical value of this imaging modality in staging, restaging, and surveillance for patients with multiple myeloma. PMID:27761300
Clinical Utility of Positron Emission Tomography Magnetic Resonance Imaging (PET-MRI) in Gastrointestinal Cancers.
Matthews, Robert; Choi, Minsig
Anatomic imaging utilizing both CT (computed tomography) and MRI (magnetic resonance imaging) limits the assessment of cancer metastases in lymph nodes and distant organs while functional imaging like PET (positron emission tomography) scan has its limitation in spatial resolution capacity. Hybrid imaging utilizing PET-CT and PET-MRI are novel imaging modalities that are changing the current landscape in cancer diagnosis, staging, and treatment response. MRI has shown to have higher sensitivity in soft tissue, head and neck pathology, and pelvic disease, as well as, detecting small metastases in the liver and bone compared to CT. Combining MRI with PET allows for detection of metastases that may have been missed with current imaging modalities. In this review, we will examine the clinical utility of FDG PET-MRI in the diagnosis and staging of gastrointestinal cancers with focus on esophageal, stomach, colorectal, and pancreatic cancers. We will also explore its role in treatment response and future directions associated with it.
An Application of Micro-channel Plate Photomultiplier Tube to Positron Emission Tomography.
Kim, H; Chen, C-T; Frisch, H; Tang, F; Kao, C-M
We are developing a Time-of-Flight Positron Emission Tomography detector using flat panel micro-channel plate photomultiplier tubes (MCP PMT). The high-speed waveform sampling data acquisition is adopted to exploit the fast time response of MCP PMT efficiently by using transmission-line readout scheme. To demonstrate the feasibility of the proposed detector, prototype detector modules were built using Photonis XP85022 MCP PMT, transmission-line board (TL), and high-speed waveform sampling electronics equipped with DRS4 chips. The MCP/TL module was coupled to single LYSO crystal, and experimental tests have been conducted in a coincidence setup to measure the responses to 511 keV annihilation photon. The details of the prototype module, experimental setup, and the preliminary results are presented and discussed.
An Application of Micro-channel Plate Photomultiplier Tube to Positron Emission Tomography
Kim, H.; Chen, C.-T.; Frisch, H.; Tang, F.; Kao, C.-M.
We are developing a Time-of-Flight Positron Emission Tomography detector using flat panel micro-channel plate photomultiplier tubes (MCP PMT). The high-speed waveform sampling data acquisition is adopted to exploit the fast time response of MCP PMT efficiently by using transmission-line readout scheme. To demonstrate the feasibility of the proposed detector, prototype detector modules were built using Photonis XP85022 MCP PMT, transmission-line board (TL), and high-speed waveform sampling electronics equipped with DRS4 chips. The MCP/TL module was coupled to single LYSO crystal, and experimental tests have been conducted in a coincidence setup to measure the responses to 511 keV annihilation photon. The details of the prototype module, experimental setup, and the preliminary results are presented and discussed. PMID:23227135
Micropixel avalanche photodiodes and the possibility for their application in positron-emission tomography
NASA Astrophysics Data System (ADS)
Anfimov, N. V.; Selyunin, A. S.
Micropixel avalanche photodiodes (MAPDs) are new instruments for detecting low-intensity light. They consist of many microcounters (pixels integrated on a common silicon wafer). A unique design by the Joint Institute for Nuclear Research (JINR) (Z. Sadygov)—deep-microwell MAPD—provides an order of larger pixel densities without losses in photon-detection efficiency. These instruments are beginning to find use in precision electromagnetic calorimetry. MAPDs can be most widely applied as photodetectors in scanners for positron-emission tomographs (PETs), particularly the time-of-flight PETs becoming popular now. The possibility of using MAPDs in PETs is shown, and the time resolution of a pair of quanta detected by Lutetium Fine Silicate scintillation crystals with MAPD readout is obtained at the level of 400 ps.
Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography
Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr. ); Gillin, J.C. )
The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep.
[Inflammatory activity in Takayasu arteritis. Detection through positron emission tomography (PET)].
Alexánderson, Erick; Soto, María Elena; Ricalde, Alejandro; Meave, Aloha; Reyes, Pedro
Takayasu arteritis (TA) is a chronic disease that affects mainly the aorta. Its etiology is still unknown, nevertheless it predominates in women and initiates primarily in the youth. This disease seems to have two different stages, an early stage that is characterized by an inflammatory process and a later stage characterized by vascular occlusion. Unitl now, diagnosis and classification of TA are made clinically, based on ACR; criteria and imaging studies as computed tomography and aorta angiographies. Currently, new imaging, non invasive studies, such as magnetic resonance (MRI) and positron emission tomography (PET) are being used. PET technique could be helpful in the diagnosis and detection of inflammatory activity in patients with TA because of its capacity to detect increased metabolism. We present the case of a female patient with TA diagnosis, which demonstrated clinical inflammatory activity that was corroborated by laboratory studies, MRI and PET. PMID:15909745
Regional brain glucose metabolism in chronic schizophrenia. A positron emission transaxial tomographic study
Farkas, T.; Wolf, A.P.; Jaeger, J.; Brodie, J.D.; Christman, D.R.; Fowler, J.S.
Thirteen diagnosed schizophrenics and 11 normal controls were studied with a method using the PETT III positron emission tomograph (PET) and fluorodeoxyglucose labeled with fluorine 18. Each subject also had a computed tomographic (CT) scan. For each subject, two brain levels, one through the basal ganglia and one through the semioval center, were analyzed for the mean regional metabolic glucose rate. Specifically, relationships between frontal and posterior regions were evaluated. The CT scans of matching levels were superimposed on the functional PET images to provide anatomic criteria for region of interest selection. While no whole-slice metabolic differences were apparent between groups, schizophrenics had significantly lower activity in the frontal lobes, relative to posterior regions. The medicated and drug-free groups did not differ from one another in these regards. Trait v state dependency of the phenomenon was analyzed, and several technological limitations were considered.
Receptor-specific positron emission tomography radiopharmaceuticals: /sup 75/Br-labeled butyrophenone neuroleptics
Moerlein, S.M.; Stoecklin, G.; Weinhard, K.; Pawlik, G.; Heiss, W.D.
Cerebral dopaminergic D/sub 2/ receptors are involved in several common disease states, such as schizophrenia, Parkinson's disease, and Huntington's chorea. The use of radiolabeled D/sub 2/ receptor-binding ligands with positron emission tomography (PET) to noninvasively quantitate D/sub 2/ receptor densities thus has potential application in medicine. Butyrophenone neuroleptics have a high in vitro and in vivo binding affinity for cerebral D/sub 2/ receptors, and due to the useful chemical and nuclear decay properties of /sup 74/Br (76% ..beta../sup +/, half-life = 1.6 h), the authors have evaluated radiobrominated bromospiperone (BSP), brombenperidol (BBP), and bromperidol (BP) as radiopharmaceuticals for use with PET.
Caffeine and human cerebral blood flow: A positron emission tomography study
Cameron, O.G.; Modell, J.G.; Hariharan, M. )
Positron emission tomography (PET) was used to quantify the effect of caffeine on whole brain and regional cerebral blood flow (CBF) in humans. A mean dose of 250 mg of caffeine produced approximately a 30% decrease in whole brain CBF; regional differences in caffeine effect were not observed. Pre-caffeine CBF strongly influenced the magnitude of the caffeine-induced decrease. Caffeine decreased p{sub a}CO{sub 2} and increased systolic blood pressure significantly; the change in p{sub a}CO{sub 2} did not account for the change in CBF. Smaller increases in diastolic blood pressure, heart rate, plasma epinephrine and norepinephrine, and subjectively reported anxiety were also observed.
Comparison of kinetic models for data from a positron emission tomograph
Coxson, P.G.; Huesman, R.H.; Lim, S.; Klein, G.J.; Reutter, B.W.; Budinger, T.F.
The purpose of this research was to compare a physiological model of {sup 82}Rb in the myocardium with two reduced order models with regard to their ability to assess physiological parameters of diagnostic significance. A three compartment physiological model of {sup 82}Rb uptake in the myocardium was used to simulate kinetic region of interest data from a positron emission tomograph (PET). Simulations were generated for eight different blood flow rates reflecting the physiological range of interest. Two reduced order models which are commonly used with myocardial PET studies were fit to the simulated data and the parameters of the reduced order models were compared with the physiological parameters. Then all three models were fit to the simulated data with noise added. Monte Carlo simulations were used to evaluate and compare the diagnostic utility of the reduced order models.
Unusual case of infantile fibrosarcoma evaluated on F-18 fluorodeoxyglucose positron emission tomography-computed tomography
Bedmutha, Akshay; Singh, Natasha; Shivdasani, Divya; Gupta, Nitin
Infantile fibrosarcoma (IFS) is a rare soft-tissue sarcoma originating from extremities and occasionally from axial soft tissue. The prognosis is good with favorable long-term survival. It is rarely metastasizing tumor, the chances being lesser with IFS originating from extremities. Use of neoadjuvant chemotherapy (NACT) as a treatment regime further reduces the chances of local relapse and distant metastasis. The organs commonly affected in metastatic IFS are lungs and lymph nodes. We report an unusual case of an IFS originating from extremity, which received NACT, yet presented with an early metastatic disease involving soft tissues and sparing lungs and lymph nodes, as demonstrated on fluorodeoxyglucose positron emission tomography-computed tomography. PMID:27385891
Myelin imaging with C-11 labeled diphenylmethanol and positron emission tomography
Herscovitch, P.; Dischino, D.D.; Kilbourn, M.R.; Welch, M.J.; Raichle, M.E.
The authors have recently studied several C-11-labeled radiopharmaceuticals for their suitability as myelin imaging agents with positron emission tomography (PET). C-11 diphenylmethanol (DPM) was selected on the basis of its in vivo metabolic stability and high extraction and lipophilicity. PET studies were performed in three normal subjects and in one patient with multiple sclerosis (MS). Myelin distribution was imaged following the bolus intravenous administration of 25-30 mCi of C-11 DPM. Sequential scans were obtained after radiotracer administration to measure the DPM distribution as a function of time. In addition, regional cerebral blood flow was measured after the bolus intravenous injection of 0-15 water. A tomographic slice through the centrum semiovale was used to obtain regional data for gray matter (GM) and white matter (WM).
Initial characterization of a position-sensitive photodiode/BGO detector for PET (positron emission tomography)
Derenzo, S.E.; Moses, W.W.; Jackson, H.G.; Turko, B.T.; Cahoon, J.L.; Geyer, A.B.; Vuletich, T.
We present initial results of a position-sensitive photodiode/BGO detector for high resolution, multi-layer positron emission tomography (PET). Position sensitivity is achieved by dividing the 3 mm /times/ 20 mm rectangular photosensitive area along the diagonal to form two triangular segments. Each segment was individually connected to a low-noise amplifier. The photodiodes and crystals were cooled to /minus/100/degree/C to reduce dark current and increase the BGO signal. With an amplifier peaking time of 17 ..mu..sec, the sum of the signals (511 keV photopeak) was 3200 electrons with a full width at half maximum (fwhm) of 750 electrons. The ratio of one signal to the sum determined the depth of interaction with a resolution of 11 mm fwhm. 27 refs., 7 figs.
The nigrostriatal dopaminergic pathway in Wilson's disease studied with positron emission tomography.
Snow, B J; Bhatt, M; Martin, W R; Li, D; Calne, D B
Movement disorders, including Parkinsonism, are prominent features of neurological Wilson's disease (WD). This suggests there may be dysfunction of the nigrostriatal dopaminergic pathway. To explore this possibility, five patients were studied using positron emission tomography (PET) with 18F-6-fluorodopa (6FD), and magnetic resonance imaging (MRI). We calculated striatal 6FD uptake rate constants by a graphical method and compared the results with those of 18 normal subjects. It was found that four patients with symptoms all had abnormally low 6FD uptake, and the one asymptomatic patient had normal uptake. PET evidence for nigrostriatal dopaminergic dysfunction was present even after many years of penicillamine treatment. It is concluded that the nigrostriatal dopaminergic pathway is involved in neurological WD. Images PMID:1901347
Image properties of list mode likelihood reconstruction for a rectangular positron emission mammography with DOI measurements
Qi, Jinyi; Klein, Gregory J.; Huesman, Ronald H.
A positron emission mammography scanner is under development at our Laboratory. The tomograph has a rectangular geometry consisting of four banks of detector modules. For each detector, the system can measure the depth of interaction information inside the crystal. The rectangular geometry leads to irregular radial and angular sampling and spatially variant sensitivity that are different from conventional PET systems. Therefore, it is of importance to study the image properties of the reconstructions. We adapted the theoretical analysis that we had developed for conventional PET systems to the list mode likelihood reconstruction for this tomograph. The local impulse response and covariance of the reconstruction can be easily computed using FFT. These theoretical results are also used with computer observer models to compute the signal-to-noise ratio for lesion detection. The analysis reveals the spatially variant resolution and noise properties of the list mode likelihood reconstruction. The theoretical predictions are in good agreement with Monte Carlo results.
A case of sarcoidosis diagnosed by positron emission tomography/computed tomography
Aksoy, Sabire Yilmaz; Özdemir, Elif; Sentürk, Aysegül; Türkölmez, Seyda
Sarcoidosis is a multisystem granulomatous disorder of unknown cause which may affect any organ or system but primarily involve the lungs and the lymphatic system. Extrapulmonary sarcoidosis represents approximately 30-50% of patients. We report the case of a 51-year-old female who presented with increasing complaints of a cough, weakness, weight loss, and chest pain and who was found to have a suspicious lesion on thorax computed tomography(CT). Fluorodeoxyglucose (FDG) positron emission tomography/CT performed for diagnostic purposes demonstrated increased FDG accumulation at the bilateral enlarged parotid and lacrimal gland and in the reticulonodular infiltration area located in the left lung as well as multiple lymphadenopathies with increased FDG accumulation. There were also hepatosplenomegaly and splenic uptake. Skin biopsy showed noncaseating granulomas, and the patient was diagnosed as stage 2 sarcoidosis. PMID:27385890
18F-FDG positron emission tomography in oncology: main indications.
Vercher-Conejero, J L; Gámez Cenzano, C
The development of molecular and functional imaging with new imaging techniques such as computed tomography, magnetic resonance imaging, and positron emission tomography (PET) among others, has greatly improved the detection of tumors, tumor staging, and the detection of possible recurrences. Furthermore, the combination of these different imaging modalities and the continual development of radiotracers for PET have advanced our understanding and knowledge of the different pathophysiological processes in cancer, thereby helping to make treatment more efficacious, improving patients' quality of life, and increasing survival. PET is one of the imaging techniques that has attracted the most interest in recent years for its diagnostic capabilities. Its ability to anatomically locate pathologic foci of metabolic activity has revolutionized the detection and staging of many tumors, exponentially broadening its potential indications not only in oncology but also in other fields such as cardiology, neurology, and inflammatory and infectious diseases. PMID:27184919
An 8×8 Row-Column Summing Readout Electronics for Preclinical Positron Emission Tomography Scanners.
Shih, Y C; Sun, F W; Macdonald, L R; Otis, B P; Miyaoka, R S; McDougald, W; Lewellen, T K
This work presents a row/column summing readout electronics for an 8×8 silicon photomultiplier array. The summation circuit greatly reduces the number of electronic channels, which is desirable for pursuing higher resolution positron emission tomography scanners. By using a degenerated common source topology in the summation circuit, more fan-in is possible and therefore a greater reduction in the number of electronic channels can be achieved. The timing signal is retrieved from a common anode, which allows the use of a single fast-sampling analog to digital converter (ADC) for the timing channel and slower, lower power ADCs for the 64 spatial channels. Preliminary results of one row summation of the 8×8 readout electronics exhibited FWHM energy resolution of 17.8% and 18.3% with and without multiplexing, respectively. The measured timing resolution is 2.9ns FWHM.
18F-FDG positron emission tomography in oncology: main indications.
Vercher-Conejero, J L; Gámez Cenzano, C
The development of molecular and functional imaging with new imaging techniques such as computed tomography, magnetic resonance imaging, and positron emission tomography (PET) among others, has greatly improved the detection of tumors, tumor staging, and the detection of possible recurrences. Furthermore, the combination of these different imaging modalities and the continual development of radiotracers for PET have advanced our understanding and knowledge of the different pathophysiological processes in cancer, thereby helping to make treatment more efficacious, improving patients' quality of life, and increasing survival. PET is one of the imaging techniques that has attracted the most interest in recent years for its diagnostic capabilities. Its ability to anatomically locate pathologic foci of metabolic activity has revolutionized the detection and staging of many tumors, exponentially broadening its potential indications not only in oncology but also in other fields such as cardiology, neurology, and inflammatory and infectious diseases.
Combined positron emission tomography and computed tomography to visualize and quantify fluid flow in sedimentary rocks
NASA Astrophysics Data System (ADS)
Fernø, M. A.; Gauteplass, J.; Hauge, L. P.; Abell, G. E.; Adamsen, T. C. H.; Graue, A.
Here we show for the first time the combined positron emission tomography (PET) and computed tomography (CT) imaging of flow processes within porous rocks to quantify the development in local fluid saturations. The coupling between local rock structure and displacement fronts is demonstrated in exploratory experiments using this novel approach. We also compare quantification of 3-D temporal and spatial water saturations in two similar CO2 storage tests in sandstone imaged separately with PET and CT. The applicability of each visualization technique is evaluated for a range of displacement processes, and the favorable implementation of combining PET/CT for laboratory core analysis is discussed. We learn that the signal-to-noise ratio (SNR) is over an order of magnitude higher for PET compared with CT for the studied processes.
Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons
Biegon, A.; Biegon, A.; Kim, S.-W.; Logan, J.; Hooker, J.M.; Muench, L.; Fowler, J.S.
Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor [{sup 11}C]vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Nicotine administration produced significant, dose-dependent reductions in [{sup 11}C]vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.
Measurement of blood-brain barrier permeability with positron emission tomography and (68Ga)EDTA
Kessler, R.M.; Goble, J.C.; Bird, J.H.; Girton, M.E.; Doppman, J.L.; Rapoport, S.I.; Barranger, J.A.
Positron emission tomography (PET) was employed to examine time-dependent changes in blood-brain barrier (BBB) permeability to (68Ga)ethylenediaminetetraacetate (EDTA) in the rhesus monkey, following reversible barrier opening by intracarotid infusion of a hypertonic mannitol solution. The PET technique, when combined with measurements of plasma radioactivity, provided a quantitative measure of the cerebrovascular permeability-area product (PA) at different times following mannitol infusion. Hypertonic mannitol treatment reversibly increased PA to (68Ga)EDTA more than 10-fold; much of the barrier effect was over by 10 min after mannitol treatment. The results show that PET can be used to measure transient changes in BBB integrity in specific brain regions, under in vivo, noninvasive conditions.
Patterns of brain activity in normals and schizophrenics with positron emission tomography
Volkow, N.D.; Wolf, A.P.; Gomez-Mont, F.; Brodie, J.D.; Canero, R.; Van Gelder, P.; Russell, J.A.G.
The authors investigated the functional interaction among brain areas under baseline and upon activation by a visual task to compare the response of normal subjects from the ones of chronic schizophrenics. Cerebral metabolic images were obtained on twelve healthy volunteers an eighteen schizophrenics with positron emission tomography and 11-C-Deoxyglucose. Correlation coefficients among the relative metabolic values (region of interest divided by the average of whole brain gray matter) of 11 brain regions; frontal, parietal, temporal and occipital left and right lobes, left and right basal ganglia and thalamus were computed for the baseline and for the task. Under baseline, normals showed more functional correlations than schizophrenics. Both groups showed a thalamo-occipital (positive) and thalamo-frontal (negative) interaction. The highest correlations among homologous brain areas were the frontal, occipital and basal ganglia.
Sparse representation and dictionary learning penalized image reconstruction for positron emission tomography
NASA Astrophysics Data System (ADS)
Chen, Shuhang; Liu, Huafeng; Shi, Pengcheng; Chen, Yunmei
Accurate and robust reconstruction of the radioactivity concentration is of great importance in positron emission tomography (PET) imaging. Given the Poisson nature of photo-counting measurements, we present a reconstruction framework that integrates sparsity penalty on a dictionary into a maximum likelihood estimator. Patch-sparsity on a dictionary provides the regularization for our effort, and iterative procedures are used to solve the maximum likelihood function formulated on Poisson statistics. Specifically, in our formulation, a dictionary could be trained on CT images, to provide intrinsic anatomical structures for the reconstructed images, or adaptively learned from the noisy measurements of PET. Accuracy of the strategy with very promising application results from Monte-Carlo simulations, and real data are demonstrated.
A case of sarcoidosis diagnosed by positron emission tomography/computed tomography.
Aksoy, Sabire Yilmaz; Özdemir, Elif; Sentürk, Aysegül; Türkölmez, Seyda
Sarcoidosis is a multisystem granulomatous disorder of unknown cause which may affect any organ or system but primarily involve the lungs and the lymphatic system. Extrapulmonary sarcoidosis represents approximately 30-50% of patients. We report the case of a 51-year-old female who presented with increasing complaints of a cough, weakness, weight loss, and chest pain and who was found to have a suspicious lesion on thorax computed tomography(CT). Fluorodeoxyglucose (FDG) positron emission tomography/CT performed for diagnostic purposes demonstrated increased FDG accumulation at the bilateral enlarged parotid and lacrimal gland and in the reticulonodular infiltration area located in the left lung as well as multiple lymphadenopathies with increased FDG accumulation. There were also hepatosplenomegaly and splenic uptake. Skin biopsy showed noncaseating granulomas, and the patient was diagnosed as stage 2 sarcoidosis. PMID:27385890
An 8×8 Row-Column Summing Readout Electronics for Preclinical Positron Emission Tomography Scanners
Shih, Y. C.; Sun, F. W.; MacDonald, L. R.; Otis, B. P.; Miyaoka, R. S.; McDougald, W.; Lewellen, T. K.
This work presents a row/column summing readout electronics for an 8×8 silicon photomultiplier array. The summation circuit greatly reduces the number of electronic channels, which is desirable for pursuing higher resolution positron emission tomography scanners. By using a degenerated common source topology in the summation circuit, more fan-in is possible and therefore a greater reduction in the number of electronic channels can be achieved. The timing signal is retrieved from a common anode, which allows the use of a single fast-sampling analog to digital converter (ADC) for the timing channel and slower, lower power ADCs for the 64 spatial channels. Preliminary results of one row summation of the 8×8 readout electronics exhibited FWHM energy resolution of 17.8% and 18.3% with and without multiplexing, respectively. The measured timing resolution is 2.9ns FWHM. PMID:20729983
Clinical use of amyloid-positron emission tomography neuroimaging: Practical and bioethical considerations.
Witte, Michael M; Foster, Norman L; Fleisher, Adam S; Williams, Monique M; Quaid, Kimberly; Wasserman, Michael; Hunt, Gail; Roberts, J Scott; Rabinovici, Gil D; Levenson, James L; Hake, Ann Marie; Hunter, Craig A; Van Campen, Luann E; Pontecorvo, Michael J; Hochstetler, Helen M; Tabas, Linda B; Trzepacz, Paula T
Until recently, estimation of β-amyloid plaque density as a key element for identifying Alzheimer's disease (AD) pathology as the cause of cognitive impairment was only possible at autopsy. Now with amyloid-positron emission tomography (amyloid-PET) neuroimaging, this AD hallmark can be detected antemortem. Practitioners and patients need to better understand potential diagnostic benefits and limitations of amyloid-PET and the complex practical, ethical, and social implications surrounding this new technology. To complement the practical considerations, Eli Lilly and Company sponsored a Bioethics Advisory Board to discuss ethical issues that might arise from clinical use of amyloid-PET neuroimaging with patients being evaluated for causes of cognitive decline. To best address the multifaceted issues associated with amyloid-PET neuroimaging, we recommend this technology be used only by experienced imaging and treating physicians in appropriately selected patients and only in the context of a comprehensive clinical evaluation with adequate explanations before and after the scan. PMID:27239516
Positron emission tomography imaging as a key enabling technology in drug development.
McCarthy, T J
The use of positron emission tomography (PET) in drug development has become more common in the pharmaceutical industry in recent years. One of the biggest challenges to gaining acceptance of this technology is for project teams to understand when to use PET. This chapter reviews the usage of PET in drug development in the context of target, mechanism and efficacy biomarkers. Examples are drawn from a number of therapeutic areas, but we also show that the relative penetration of this technology beyond CNS and oncology applications has been relatively small. However, with the increasing availability of PET and development of novel radiotracers it is expected that the utilization will be much broader in future years, with the additional expectation that the use of PET as an efficacy biomarker will also become more evident. PMID:17172162
Positron emission tomography radioligands for in vivo imaging of Aβ plaques
Mason, N. Scott; Mathis, Chester A.; Klunk, William E.
The development of positron emission tomography (PET) radioligands for the non-invasive imaging of amyloid-β plaque burden has been the focus of intense research efforts over the last decade. A variety of structural backbones have been investigated and several radiolabeled molecules have been evaluated in phase I (and later) clinical studies. These efforts have been driven by the desire not only to develop a suitable diagnostic imaging agent but also to develop a means to evaluate potential therapies for Alzheimer's disease. This review focuses on the development of these ligands, as well as the radiochemistry and current regulatory status of these PET radioligands. Particular attention is given to those ligands that have progressed to the later stages of drug development (phase II/III clinical trial studies) or approved New Drug Application status. PMID:24285314
Hemiballismus: Study of a case using positron emission tomography with 18fluoro-2-deoxyglucose
Dubinsky, R.M.; Greenberg, M.; Di Chiro, G.; Baker, M.; Hallett, M. )
A 64-year-old man had right-sided persistent hemiballismus. Cerebral computed tomography (CT) and 0.5-T magnetic resonance imaging (MRI) showed no abnormalities, but 1.5-T MRI showed decreased signal intensity of the putamina, greater on the left than on the right. The subthalamic area was normal on CT and MRI. Positron emission tomography with 18fluoro2-deoxyglucose showed marked hypometabolism of the left putamen (60% of the right) and hypermetabolism of the left parietal lobe (138% of the right). The decreased metabolism of the left putamen may indicate a reduction in neuronal firing. The pathophysiology of the hemiballismus in this case may be loss of tonic inhibition of the lateral globus pallidus from the putamen, leading in turn to greater inhibition of the subthalamic nucleus, less excitation of the medial globus pallidus, and less inhibition of the thalamus and motor cortex, and thus allowing expression of the ballistic movements.
Optical imaging of reporter gene expression using a positron-emission-tomography probe
NASA Astrophysics Data System (ADS)
Liu, Hongguang; Ren, Gang; Liu, Shuanglong; Zhang, Xiaofen; Chen, Luxi; Han, Peizhen; Cheng, Zhen
Reporter gene/reporter probe technology is one of the most important techniques in molecular imaging. Lately, many reporter gene/reporter probe systems have been coupled to different imaging modalities such as positron emission tomography (PET) and optical imaging (OI). It has been recently found that OI techniques could be used to monitor radioactive tracers in vitro and in living subjects. In this study, we further demonstrate that a reporter gene/nuclear reporter probe system [herpes simplex virus type-1 thymidine kinase (HSV1-tk) and 9-(4-18F-fluoro-3-[hydroxymethyl] butyl) guanine ([18F]FHBG)] could be successfully imaged by OI in vitro and in vivo. OI with radioactive reporter probes will facilitate and broaden the applications of reporter gene/reporter probe techniques in medical research.
Design and evaluation of HEADTOME-IV, a whole-body positron emission tomograph
Iida, H.; Miura, S.; Kanno, I.; Murakami, M.; Takahashi, K.; Uemura, K.
A whole body positron emission tomograph HEADTOME-IV has been developed, and its physical performances were investigated. The in-plane spatial resolution of 4.5 mm was realized with stationary-sampling at the center of the field-of-view. The axial slice thickness was 9.5 and 9.0-mm for direct and cross planes, respectively. By moving the gantry framework axially, transaxial images of 14 or 21 slices are obtained quasi-simultaneously. The realtime-operation large-scale cache memory system was effective to realize realtime corrections for deadtime and radionuclide decay, and realtime weighted integration for the purpose of a rapid calculation of rate-constant images.
Greater left cerebral hemispheric metabolism in bulimia assessed by positron emission tomography
Wu, J.C.; Hagman, J.; Buchsbaum, M.S.; Blinder, B.; Derrfler, M.; Tai, W.Y.; Hazlett, E.; Sicotte, N. )
Eight women with bulimia and eight age- and sex-matched normal control subjects were studied with positron emission tomography using (18F)-fluorodeoxyglucose (FDG) as a tracer of brain metabolic rate. Subjects performed a visual vigilance task during FDG uptake. In control subjects, the metabolic rate was higher in the right hemisphere than in the left, but patients with bulimia did not have this normal asymmetry. Lower metabolic rates in the basal ganglia, found in studies of depressed subjects, and higher rates in the basal ganglia, reported in a study of anorexia nervosa, were not found. This is consistent with the suggestion that bulimia is a diagnostic grouping distinct from these disorders.
Integration of Quantitative Positron Emission Tomography Absolute Myocardial Blood Flow Measurements in the Clinical Management of Coronary Artery Disease.
Gewirtz, Henry; Dilsizian, Vasken
In the >40 years since planar myocardial imaging with(43)K-potassium was introduced into clinical research and management of patients with coronary artery disease (CAD), diagnosis and treatment have undergone profound scientific and technological changes. One such innovation is the current state-of-the-art hardware and software for positron emission tomography myocardial perfusion imaging, which has advanced it from a strictly research-oriented modality to a clinically valuable tool. This review traces the evolving role of quantitative positron emission tomography measurements of myocardial blood flow in the evaluation and management of patients with CAD. It presents methodology, currently or soon to be available, that offers a paradigm shift in CAD management. Heretofore, radionuclide myocardial perfusion imaging has been primarily qualitative or at best semiquantitative in nature, assessing regional perfusion in relative terms. Thus, unlike so many facets of modern cardiovascular practice and CAD management, which depend, for example, on absolute values of key parameters such as arterial and left ventricular pressures, serum lipoprotein, and other biomarker levels, the absolute levels of rest and maximal myocardial blood flow have yet to be incorporated into routine clinical practice even in most positron emission tomography centers where the potential to do so exists. Accordingly, this review focuses on potential value added for improving clinical CAD practice by measuring the absolute level of rest and maximal myocardial blood flow. Physiological principles and imaging fundamentals necessary to understand how positron emission tomography makes robust, quantitative measurements of myocardial blood flow possible are highlighted.
Detection of lung cancer in patients with pneumoconiosis by fluorodeoxyglucose-positron emission tomography/computed tomography: four cases.
Yu, Hua; Zhang, Hua; Wang, Yanli; Cui, Xinjian; Han, Jiankui
We report 4 cases of lung cancer in patients with pneumoconiosis detected by F18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), which could differentiate lung cancer and pneumoconiosis. FDG-PET/CT may be useful in cancer screening for patients with pneumoconiosis.
Combined computed tomography and fluorodeoxyglucose positron emission tomography in the diagnosis of prosthetic valve endocarditis: a case series
Background The diagnosis of prosthetic valve endocarditis is challenging. The gold standard for prosthetic valve endocarditis diagnosis is trans-esophageal echocardiography. However, trans-esophageal echocardiography may result in negative findings or yield images difficult to differentiate from thrombus in patients with prosthetic valve endocarditis. Combined computed tomography and fluorodeoxyglucose positron emission tomography is a potentially promising diagnostic tool for several infectious conditions and it has also been employed in patients with prosthetic valve endocarditis but data are still scant. Case presentations We reviewed the charts of 6 patients with prosthetic aortic valves evaluated for suspicion of prosthetic valve endocarditis, at two different hospital, over a 3-year period. We found 3 patients with early-onset PVE cases and blood cultures yielding Pseudomonas aeruginosa, Staphylococcus epidermidis and Staphylococcus lugdunensis, respectively; and 3 late-onset cases in the remaining 3 patients with isolation in the blood of Streptococcus bovis, Candida albicans and P. aeruginosa, respectively. Initial trans-esophageal echocardiography was negative in all the patients, while fluorodeoxyglucose positron emission tomography showed images suspicious for prosthetic valve endocarditis. In 4 out of 6 patients valve replacement was done with histology confirming the prosthetic valve endocarditis diagnosis. After an adequate course of antibiotic therapy fluorodeoxyglucose positron emission tomography showed resolution of prosthetic valve endocarditis in all the patients. Conclusion Our experience confirms the potential role of fluoroseoxyglucose positron emission tomography in the diagnosis and follow-up of prosthetic valve endocarditis. PMID:24418206
Integration of Quantitative Positron Emission Tomography Absolute Myocardial Blood Flow Measurements in the Clinical Management of Coronary Artery Disease.
Gewirtz, Henry; Dilsizian, Vasken
In the >40 years since planar myocardial imaging with(43)K-potassium was introduced into clinical research and management of patients with coronary artery disease (CAD), diagnosis and treatment have undergone profound scientific and technological changes. One such innovation is the current state-of-the-art hardware and software for positron emission tomography myocardial perfusion imaging, which has advanced it from a strictly research-oriented modality to a clinically valuable tool. This review traces the evolving role of quantitative positron emission tomography measurements of myocardial blood flow in the evaluation and management of patients with CAD. It presents methodology, currently or soon to be available, that offers a paradigm shift in CAD management. Heretofore, radionuclide myocardial perfusion imaging has been primarily qualitative or at best semiquantitative in nature, assessing regional perfusion in relative terms. Thus, unlike so many facets of modern cardiovascular practice and CAD management, which depend, for example, on absolute values of key parameters such as arterial and left ventricular pressures, serum lipoprotein, and other biomarker levels, the absolute levels of rest and maximal myocardial blood flow have yet to be incorporated into routine clinical practice even in most positron emission tomography centers where the potential to do so exists. Accordingly, this review focuses on potential value added for improving clinical CAD practice by measuring the absolute level of rest and maximal myocardial blood flow. Physiological principles and imaging fundamentals necessary to understand how positron emission tomography makes robust, quantitative measurements of myocardial blood flow possible are highlighted. PMID:27245647
Positron Emission Tomography of Brain β-Amyloid and Tau Levels in Adults With Down Syndrome
Nelson, Linda D.; Siddarth, Prabha; Kepe, Vladimir; Scheibel, Kevin E.; Huang, S. C.; Barrio, Jorge R.; Small, Gary W.
Objectives To determine the neuropathological load in the living brain of nondemented adults with Down syndrome using positron emission tomography with 2-(1-{6-[(2-fluorine 18–labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([18F]FDDNP) and to assess the influence of age and cognitive and behavioral functioning. For reference, [18F]FDDNP binding values and patterns were compared with those from patients with Alzheimer disease and cognitively intact control participants. Design Cross-sectional clinical study. Participants Volunteer sample of 19 persons with Down syndrome without dementia (mean age, 36.7 years), 10 patients with Alzheimer disease (mean age, 66.5 years), and 10 controls (mean age, 43.8 years). Main Outcome Measures Binding of [18F]FDDNP in brain regions of interest, including the parietal, medial temporal, lateral temporal, and frontal lobes and posterior cingulate gyrus, and the average of all regions (global binding). Results The [18F]FDDNP binding values were higher in all brain regions in the Down syndrome group than in controls. Compared with the Alzheimer disease group, the Down syndrome group had higher [18F]FDDNP binding values in the parietal and frontal regions, whereas binding levels in other regions were comparable. Within the Down syndrome group, age correlated with [18F]FDDNP binding values in all regions except the posterior cingulate, and several measures of behavioral dysfunction showed positive correlations with global, frontal, parietal, and posterior cingulate [18F]FDDNP binding. Conclusions Consistent with neuropathological findings from postmortem studies, [18F]FDDNP positron emission tomography shows high binding levels in Down syndrome comparable to Alzheimer disease and greater levels than in members of a control group. The positive associations between [18F]FDDNP binding levels and age as well as behavioral dysfunction in Down syndrome are consistent with the age-related progression of Alzheimer
Predicting Outcome in Patients with Rhabdomyosarcoma: Role of [{sup 18}F]Fluorodeoxyglucose Positron Emission Tomography
Casey, Dana L.; Wexler, Leonard H.; Fox, Josef J.; Dharmarajan, Kavita V.; Schoder, Heiko; Price, Alison N.; Wolden, Suzanne L.
Purpose: To evaluate whether [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) response of the primary tumor after induction chemotherapy predicts outcomes in rhabdomyosarcoma (RMS). Methods and Materials: After excluding those with initial tumor resection, 107 patients who underwent FDG-PET after induction chemotherapy at Memorial Sloan Kettering Cancer Center from 2002 to 2013 were reviewed. Local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated according to FDG-PET response and maximum standardized uptake value (SUV) at baseline (PET1/SUV1), after induction chemotherapy (PET2/SUV2), and after local therapy (PET3/SUV3). Receiver operator characteristic curves were used to determine the optimal cutoff for dichotomization of SUV1 and SUV2 values. Results: The SUV1 (<9.5 vs ≥9.5) was predictive of PFS (P=.02) and OS (P=.02), but not LC. After 12 weeks (median) of induction chemotherapy, 45 patients had negative PET2 scans and 62 had positive scans: 3-year PFS was 72% versus 44%, respectively (P=.01). The SUV2 (<1.5 vs ≥1.5) was similarly predictive of PFS (P=.005) and was associated with LC (P=.02) and OS (P=.03). A positive PET3 scan was predictive of worse PFS (P=.0009), LC (P=.05), and OS (P=.03). Conclusions: [{sup 18}F]fluorodeoxyglucose positron emission tomography is an early indicator of outcomes in patients with RMS. Future prospective trials may incorporate FDG-PET response data for risk-adapted therapy and early assessment of new treatment regimens.
Positron emission tomography demonstrates that coronary sinus retroperfusion can restore regional myocardial perfusion and preserve metabolism
O'Byrne, G.T.; Nienaber, C.A.; Miyazaki, A.; Araujo, L.; Fishbein, M.C.; Corday, E.; Schelbert, H.R. )
Positron emission tomography was used to image blood flow and metabolic tracers in risk zone myocardium after left anterior descending coronary artery occlusion during synchronized coronary venous retroperfusion. Six control and seven intervention open chest dogs had occlusion of the mid left anterior descending coronary artery. Synchronized retroperfusion commenced 25 min later. Flow tracers (rubidium-82 and nitrogen-13 ammonia) were injected retrogradely. Three hours after coronary occlusion, fluorine-18 (F-18) deoxyglucose uptake in the control and treatment groups was compared. At 200 min of occlusion, infarct size was assessed. Retrograde flow tracer uptake was observed in the risk zone in the seven intervention dogs. Fluorine-18 deoxyglucose uptake in the risk zone was increased in five of the six intervention dogs but was reduced in five of the six control dogs. The risk zone to normal zone F-18 deoxyglucose count ratio was higher in the intervention than the control group (1.13 {plus minus} 0.39 vs. 0.59 {plus minus} 0.51; p less than 0.05). The endocardial subsegment risk zone to normal zone F-18 deoxyglucose count ratio was also significantly higher in the intervention group. Percent infarction in the risk zone was 70% lower in the group treated with synchronized retroperfusion than in the control group (18.4 {plus minus} 22.6% vs. 61.2 {plus minus} 25.4%; p less than 0.02). Thus, positron emission tomography revealed that retroperfusion could deliver oxygenated blood and maintain metabolism in risk zone myocardium. Infarct size was limited to 30% of that of control. In acute closure of the left anterior descending coronary artery, synchronized retroperfusion might be considered for maintaining viability of the jeopardized myocardium if the artery cannot be reopened rapidly.
A Conway-Maxwell-Poisson (CMP) model to address data dispersion on positron emission tomography.
Santarelli, Maria Filomena; Della Latta, Daniele; Scipioni, Michele; Positano, Vincenzo; Landini, Luigi
Positron emission tomography (PET) in medicine exploits the properties of positron-emitting unstable nuclei. The pairs of γ- rays emitted after annihilation are revealed by coincidence detectors and stored as projections in a sinogram. It is well known that radioactive decay follows a Poisson distribution; however, deviation from Poisson statistics occurs on PET projection data prior to reconstruction due to physical effects, measurement errors, correction of deadtime, scatter, and random coincidences. A model that describes the statistical behavior of measured and corrected PET data can aid in understanding the statistical nature of the data: it is a prerequisite to develop efficient reconstruction and processing methods and to reduce noise. The deviation from Poisson statistics in PET data could be described by the Conway-Maxwell-Poisson (CMP) distribution model, which is characterized by the centring parameter λ and the dispersion parameter ν, the latter quantifying the deviation from a Poisson distribution model. In particular, the parameter ν allows quantifying over-dispersion (ν<1) or under-dispersion (ν>1) of data. A simple and efficient method for λ and ν parameters estimation is introduced and assessed using Monte Carlo simulation for a wide range of activity values. The application of the method to simulated and experimental PET phantom data demonstrated that the CMP distribution parameters could detect deviation from the Poisson distribution both in raw and corrected PET data. It may be usefully implemented in image reconstruction algorithms and quantitative PET data analysis, especially in low counting emission data, as in dynamic PET data, where the method demonstrated the best accuracy. PMID:27522237
Regional myocardial metabolism in patients with acute myocardial infarction assessed by positron emission tomography
Schwaiger, M.; Brunken, R.; Grover-McKay, M.; Krivokapich, J.; Child, J.; Tillisch, J.H.; Phelps, M.E.; Schelbert, H.R.
Positron emission tomography has been shown to distinguish between reversible and irreversible ischemic tissue injury. Using this technique, 13 patients with acute myocardial infarction were studied within 72 hours of onset of symptoms to evaluate regional blood flow and glucose metabolism with nitrogen (N)-13 ammonia and fluorine (F)-18 deoxyglucose, respectively. Serial noninvasive assessment of wall motion was performed to determine the prognostic value of metabolic indexes for functional tissue recovery. Segmental blood flow and glucose utilization were evaluated using a circumferential profile technique and compared with previously established semiquantitative criteria. Relative N-13 ammonia uptake was depressed in 32 left ventricular segments. Sixteen segments demonstrated a concordant decrease in flow and glucose metabolism. Regional function did not change over time in these segments. In contrast, 16 other segments with reduced blood flow revealed maintained F-18 deoxyglucose uptake consistent with remaining viable tissue. The average wall motion score improved significantly in these segments (p less than 0.01), yet the degree of recovery varied considerably among patients. Coronary anatomy was defined in 9 of 13 patients: patent infarct vessels supplied 8 of 10 segments with F-18 deoxyglucose uptake, while 10 of 13 segments in the territory of an occluded vessel showed concordant decreases in flow and metabolism (p less than 0.01). Thus, positron emission tomography reveals a high incidence of residual tissue viability in ventricular segments with reduced flow and impaired function during the subacute phase of myocardial infarction. Absence of residual tissue metabolism is associated with irreversible injury, while preservation of metabolic activity identifies segments with a variable outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative evaluation of benzodiazepine receptors in live Papio papio baboons using positron emission tomography
Brouillet, E.; Chavoix, C.; Khalili-Varasteh, M.; Bottlaender, M.; Hantraye, P.; Yorke, J.C.; Maziere, M. )
The binding of the 11C-labeled benzodiazepine antagonist Ro 15-1788 (flumazenil) was measured in the neocortex of live Papio papio baboons by positron emission tomography. This allowed us to calculate in vivo (i.e., at physiological temperature, neurotransmitters concentrations, and ionic environment) the apparent density of available benzodiazepine receptors (B'max) and the dissociation constant of Ro 15-1788 (Kd). By coadministering increasing doses of unlabeled Ro 15-1788 with (11C)Ro 15-1788 and assuming that nonsaturable radioactivity indicated the free ligand concentration, we were able to obtain saturation isotherms. We showed that a state of quasiequilibrium was reached 50 min after the administration of the radioligand. Linear Scatchard plots allowed us to calculate B'max at 78 and 50 pmol/ml of cerebral tissue in the occipital and frontal cortices, respectively. In both these areas, Kd is on the order of 6 nM, with a Hill number very close to unity. This indicates that Ro 15-1788 binds in vivo with high affinity to an homogeneous population of saturable sites. A similar measurement was carried out on a naturally photosensitive P. papio baboon. Absolute values of B'max, Kd, and Hill number were similar to those of the control baboons. Although results concerning this baboon can only be considered as a case report, this similarity may suggest that its epileptic syndrome is not related to a large change in B'max or Kd, at least in occipital and frontal cortices. Our results showed that quantitative estimation by positron emission tomography of some characteristics of benzodiazepine receptors is possible in live baboons and may represent a supplementary tool for investigating further the molecular mechanisms of benzodiazepine receptor function in physiological and physiopathological conditions.
Vision 20/20: Positron emission tomography in radiation therapy planning, delivery, and monitoring
Parodi, Katia
Positron emission tomography (PET) is increasingly considered as an effective imaging method to support several stages of radiation therapy. The combined usage of functional and morphological imaging in state-of-the-art PET/CT scanners is rapidly emerging to support the treatment planning process in terms of improved tumor delineation, and to assess the tumor response in follow-up investigations after or even during the course of fractionated therapy. Moreover, active research is being pursued on new tracers capable of providing different insights into tumor function, in order to identify areas of the planning volume which may require additional dosage for improved probability of tumor control. In this respect, major progresses in the next years will likely concern the development and clinical investigation of novel tracers and image processing techniques for reliable thresholding and segmentation, of treatment planning and beam delivery approaches integrating the PET imaging information, as well as improved multimodal clinical instrumentation such as PET/MR. But especially in the rapidly emerging case of ion beam therapy, the usage of PET is not only limited to the imaging of external tracers injected to the patient. In fact, a minor amount of positron emitters is formed in nuclear fragmentation reactions between the impinging ions and the tissue, bearing useful information for confirmation of the delivered treatment during or after therapeutic irradiation. Different implementations of unconventional PET imaging for therapy monitoring are currently being investigated clinically, and major ongoing research aims at new dedicated detector technologies and at challenging applications such as real-time imaging and time-resolved in vivo verification of motion compensated beam delivery. This paper provides an overview of the different areas of application of PET in radiation oncology and discusses the most promising perspectives in the years to come for radiation therapy
1999 ICP Distinguished Scientist Award. The history of positron emission tomography.
Nutt, Ronald
The history of Positron Emission Tomography (PET) is rich in technological achievements and advancements. The advancements that have benchmarked PET progress are the result of key components that include human intellect and passion for PET technology, relentless persuasion of key political forces to eliminate the barriers precluding PET usage, tireless efforts to raise awareness about PET and a crucial network of support throughout the PET community. This article sets forth a timeline of significant events that have contributed to the development of PET as it is known today. It introduces the earliest physicist and physician, for instance, who were responsible for the first medical applications for positron emitting radioisotopes using a simple brain probe that utilized coincidence to localize brain tumors. Additionally, it identifies landmark technological achievements that have helped pave the way to modern PET. This study includes historical accounts surrounding the use of the first human PET tomograph, discovery of the Bismuth Germanate (BGO) scintillator, development of the Fluorodeoxyglucose (FDG) PET method, the design of the first PET medical cyclotron with automated chemistry and operated by a PC and a technologist, Food and Drug Administration's approval of FDG, HCFA reimbursement, and the capacity of Lutetium Oxyorthosilicate (LSO) to produce a revolutionary advance in PET scanners. The main thrust of this article is to recognize via a timeline of PET accomplishments the noteworthy work of scientists, physicians and others who have been key players in various aspects of the continuous activity to move PET technology forward from invention to research, and to become a major clinical imaging modality.
Clustering-initiated factor analysis application for tissue classification in dynamic brain positron emission tomography
Boutchko, Rostyslav; Mitra, Debasis; Baker, Suzanne L; Jagust, William J; Gullberg, Grant T
The goal is to quantify the fraction of tissues that exhibit specific tracer binding in dynamic brain positron emission tomography (PET). It is achieved using a new method of dynamic image processing: clustering-initiated factor analysis (CIFA). Standard processing of such data relies on region of interest analysis and approximate models of the tracer kinetics and of tissue properties, which can degrade accuracy and reproducibility of the analysis. Clustering-initiated factor analysis allows accurate determination of the time–activity curves and spatial distributions for tissues that exhibit significant radiotracer concentration at any stage of the emission scan, including the arterial input function. We used this approach in the analysis of PET images obtained using 11C-Pittsburgh Compound B in which specific binding reflects the presence of β-amyloid. The fraction of the specific binding tissues determined using our approach correlated with that computed using the Logan graphical analysis. We believe that CIFA can be an accurate and convenient tool for measuring specific binding tissue concentration and for analyzing tracer kinetics from dynamic images for a variety of PET tracers. As an illustration, we show that four-factor CIFA allows extraction of two blood curves and the corresponding distributions of arterial and venous blood from PET images even with a coarse temporal resolution. PMID:25899294
Simulation study of respiratory-induced errors in cardiac positron emission tomography/computed tomography
Fitzpatrick, Gianna M.; Wells, R. Glenn
Heart disease is a leading killer in Canada and positron emission tomography (PET) provides clinicians with in vivo metabolic information for diagnosing heart disease. Transmission data are usually acquired with {sup 68}Ge, although the advent of PET/CT scanners has made computed tomography (CT) an alternative option. The fast data acquisition of CT compared to PET may cause potential misregistration problems, leading to inaccurate attenuation correction (AC). Using Monte Carlo simulations and an anthropomorphic dynamic computer phantom, this study determines the magnitude and location of respiratory-induced errors in radioactivity uptake measured in cardiac PET/CT. A homogeneous tracer distribution in the heart was considered. The AC was based on (1) a time-averaged attenuation map (2) CT maps from a single phase of the respiratory cycle, and (3) CT maps phase matched to the emission data. Circumferential profiles of the heart uptake were compared and differences of up to 24% were found between the single-phase CT-AC method and the true phantom values. Simulation results were supported by a PET/CT canine study which showed differences of up to 10% in the heart uptake in the lung-heart boundary region when comparing {sup 68}Ge- to CT-based AC with the CT map acquired at end inhalation.
Analysis of optimum diameter of orbit of transmission line source in positron emission tomograph
Yamamoto, S.; Amano, M.; Hirose, Y.; Muira, S.; Kanno, I.
Accurate attenuation correction is one of the most important factors to achieve quantitative measurements in positron emission tomography (PET). A transmission scan is most commonly used technique for the attenuation correction in PET. A difficulty in transmission scan is relatively long period to obtain a data with good signal-to-noise ratio. Insufficient signal-to-noise ratio of the transmission data limits that of emission data. Several approaches were reported to improve the transmission data. Those were (1) optimizing of detector threshold, (2) processing delayed coincidence sinogram before subtraction, filtering of transmission sinogram before performing attenuation correction, and (3) rejection of random and scatter coincidence by using rotating line source and information of its position. In some of these methods, additional calculation time or processing hardware is needed. The authors have estimated a relationship between ring diameter of a transmission line source and signal to noise ratio of the transmission dat. This paper aimes to analyze optimum diameter of the orbit of transmission line source in concerning to signal to noise ratio in transmission data.
Applications of Beta Particle Detection for Synthesis and Usage of Radiotracers Developed for Positron Emission Tomography
NASA Astrophysics Data System (ADS)
Dooraghi, Alex Abreu
Positron Emission Tomography (PET) is a noninvasive molecular imaging tool that requires the use of a radioactive compound or radiotracer which targets a molecular pathway of interest. We have developed and employed three beta particle radiation detection systems to advance PET. Specifically, the goals of these systems are to: 1. Automate dispensing of solutions containing a positron emitting isotope. 2. Monitor radioactivity on-chip during synthesis of a positron emitting radiotracer. 3. Assay cellular uptake on-chip of a positron emitting radiotracer. Automated protocols for measuring and dispensing solutions containing radioisotopes are essential not only for providing an optimum environment for radiation workers, but also to ensure a quantitatively accurate workflow. For the first project, we describe the development and performance of a system for automated radioactivity distribution of beta particle emitting radioisotopes such as fluorine-18 (F-18). Key to the system is a radiation detector in-line with a peristaltic pump. The system demonstrates volume accuracy within 5 % for volumes of 20 muL or greater. When considering volumes of 20 muL or greater, delivered radioactivity is in agreement with the requested radioactivity as measured with the dose calibrator. The integration of the detector and pump leads to a flexible system that can accurately dispense solutions containing F-18 in radioactivity concentrations directly produced from a cyclotron (~ 0.1-1 mCi/muL), to low activity concentrations intended for preclinical mouse scans (~ 1-10 muCi/muL), and anywhere in between. Electrowetting on dielectric (EWOD) is an attractive microfluidic platform for batch synthesis of PET radiotracers. Visualization of radioisotopes on-chip is critical for synthesis optimization and technological development. For the second project, we describe the development and performance of a Cerenkov/real-time imaging system for PET radiotracer synthesis on EWOD. We also investigate
Bouchet, L.; Roques, J. P.; Jourdain, E.
The 511 keV positron annihilation emission remains a mysterious component of the high energy emission of our Galaxy. Its study was one of the key scientific objectives of the SPI spectrometer on board the International Gamma-Ray Astrophysics Laboratory satellite. In fact, a lot of observing time has been dedicated to the Galactic disk with a particular emphasis on the central region. A crucial issue in such an analysis concerns the reduction technique used to treat this huge quantity of data, and more particularly the background modeling. Our method, after validation through a variety of tests, is based on detector pattern determination per {approx}6 month period, together with a normalization variable on a few hour timescale. The Galactic bulge is detected at a level of {approx}70{sigma}, allowing more detailed investigations. The main result is that the bulge morphology can be modeled with two axisymmetric Gaussians of 3.{sup 0}2 and 11.{sup 0}8 FWHM and respective fluxes of 2.5 and 5.4 x10{sup -4} photons cm{sup -2} s{sup -1}. We found a possible shift of the bulge center toward negative longitude at l = -0.{sup 0}6 {+-} 0.{sup 0}2. In addition to the bulge, a more extended structure is detected significantly with flux ranging from 1.7 to 2.9 x10{sup -3} photons cm{sup -2} s{sup -1} depending on its assumed geometry (pure disk or disk plus halo). The disk emission is also found to be symmetric within the limits of the statistical errors.
Injectable silver nanosensors: in vivo dosimetry for external beam radiotherapy using positron emission tomography
NASA Astrophysics Data System (ADS)
Christensen, A. N.; Rydhög, J. S.; Søndergaard, R. V.; Andresen, T. L.; Holm, S.; Munck Af Rosenschöld, P.; Conradsen, K.; Jølck, R. I.
Development of safe and efficient radiotherapy routines requires quantification of the delivered absorbed dose to the cancer tissue in individual patients. In vivo dosimetry can provide accurate information about the absorbed dose delivered during treatment. In the current study, a novel silver-nanosensor formulation based on poly(vinylpyrrolidinone)-coated silver nanoparticles formulated in a gelation matrix composed of sucrose acetate isobutyrate has been developed for use as an in vivo dosimeter for external beam radiotherapy. In situ photonuclear reactions trigger the formation of radioactive 106Ag, which enables post treatment verification of the delivered dose using positron emission tomography imaging. The silver-nanosensor was investigated in a tissue equivalent thorax phantom using clinical settings and workflow for both standard fractionated radiotherapy (2 Gy) and stereotactic radiotherapy (10- and 22 Gy) in a high-energy beam setting (18 MV). The developed silver-nanosensor provided high radiopacity on the planning CT-scans sufficient for patient positioning in image-guided radiotherapy and provided dosimetric information about the absorbed dose with a 10% and 8% standard deviation for the stereotactic regimens, 10 and 22 Gy, respectively.Development of safe and efficient radiotherapy routines requires quantification of the delivered absorbed dose to the cancer tissue in individual patients. In vivo dosimetry can provide accurate information about the absorbed dose delivered during treatment. In the current study, a novel silver-nanosensor formulation based on poly(vinylpyrrolidinone)-coated silver nanoparticles formulated in a gelation matrix composed of sucrose acetate isobutyrate has been developed for use as an in vivo dosimeter for external beam radiotherapy. In situ photonuclear reactions trigger the formation of radioactive 106Ag, which enables post treatment verification of the delivered dose using positron emission tomography imaging. The
A novel image reconstruction methodology based on inverse Monte Carlo analysis for positron emission tomography
NASA Astrophysics Data System (ADS)
Kudrolli, Haris A.
A three dimensional (3D) reconstruction procedure for Positron Emission Tomography (PET) based on inverse Monte Carlo analysis is presented. PET is a medical imaging modality which employs a positron emitting radio-tracer to give functional images of an organ's metabolic activity. This makes PET an invaluable tool in the detection of cancer and for in-vivo biochemical measurements. There are a number of analytical and iterative algorithms for image reconstruction of PET data. Analytical algorithms are computationally fast, but the assumptions intrinsic in the line integral model limit their accuracy. Iterative algorithms can apply accurate models for reconstruction and give improvements in image quality, but at an increased computational cost. These algorithms require the explicit calculation of the system response matrix, which may not be easy to calculate. This matrix gives the probability that a photon emitted from a certain source element will be detected in a particular detector line of response. The ``Three Dimensional Stochastic Sampling'' (SS3D) procedure implements iterative algorithms in a manner that does not require the explicit calculation of the system response matrix. It uses Monte Carlo techniques to simulate the process of photon emission from a source distribution and interaction with the detector. This technique has the advantage of being able to model complex detector systems and also take into account the physics of gamma ray interaction within the source and detector systems, which leads to an accurate image estimate. A series of simulation studies was conducted to validate the method using the Maximum Likelihood - Expectation Maximization (ML-EM) algorithm. The accuracy of the reconstructed images was improved by using an algorithm that required a priori knowledge of the source distribution. Means to reduce the computational time for reconstruction were explored by using parallel processors and algorithms that had faster convergence rates
High-speed digitization readout of silicon photomultipliers for time of flight positron emission tomography
Ronzhin, A.; Los, S.; Martens, M.; Ramberg, E.; Kim, H.; Chen, C.; Kao, C.; Niessen, K.; Zatserklyaniy, A.; Mazzillo, M.; Carbone, B.; /SGS Thomson, Catania
We report on work to develop a system with about 100 picoseconds (ps) time resolution for time of flight positron emission tomography [TOF-PET]. The chosen photo detectors for the study were Silicon Photomultipliers (SiPM's). This study was based on extensive experience in studying timing properties of SiPM's. The readout of these devices used the commercial high speed digitizer DRS4. We applied different algorithms to get the best time resolution of 155 ps Guassian (sigma) for a LYSO crystal coupled to a SiPM. We consider the work as a first step in building a prototype TOF-PET module. The field of positron-emission-tomography (PET) has been rapidly developing. But there are significant limitations in how well current PET scanners can reconstruct images, related to how fast data can be acquired, how much volume they can image, and the spatial and temporal resolution of the generated photons. Typical modern scanners now include multiple rings of detectors, which can image a large volume of the patient. In this type of scanner, one can treat each ring as a separate detector and require coincidences only within the ring, or treat the entire region viewed by the scanner as a single 3 dimensional volume. This 3d technique has significantly better sensitivity since more photon pair trajectories are accepted. However, the scattering of photons within the volume of the patient, and the effect of random coincidences limits the technique. The advent of sub-nanosecond timing resolution detectors means that there is potentially much better rejection of scattered photon events and random coincidence events in the 3D technique. In addition, if the timing is good enough, then the origin of photons pairs can be determined better, resulting in improved spatial resolution - so called 'Time-of-Flight' PET, or TOF-PET. Currently a lot of activity has occurred in applications of SiPMs for TOF-PET. This is due to the devices very good time resolution, low profile, lack of high voltage
Modeling and simulation of Positron Emission Mammography (PEM) based on double-sided CdTe strip detectors
NASA Astrophysics Data System (ADS)
Ozsahin, I.; Unlu, M. Z.
Breast cancer is the most common leading cause of cancer death among women. Positron Emission Tomography (PET) Mammography, also known as Positron Emission Mammography (PEM), is a method for imaging primary breast cancer. Over the past few years, PEMs based on scintillation crystals dramatically increased their importance in diagnosis and treatment of early stage breast cancer. However, these detectors have significant limitations like poor energy resolution resulting with false-negative result (missed cancer), and false-positive result which leads to suspecting cancer and suggests an unnecessary biopsy. In this work, a PEM scanner based on CdTe strip detectors is simulated via the Monte Carlo method and evaluated in terms of its spatial resolution, sensitivity, and image quality. The spatial resolution is found to be ~ 1 mm in all three directions. The results also show that CdTe strip detectors based PEM scanner can produce high resolution images for early diagnosis of breast cancer.
Iterative reconstruction using a Monte Carlo based system transfer matrix for dedicated breast positron emission tomography
Saha, Krishnendu; Straus, Kenneth J.; Glick, Stephen J.; Chen, Yu.
To maximize sensitivity, it is desirable that ring Positron Emission Tomography (PET) systems dedicated for imaging the breast have a small bore. Unfortunately, due to parallax error this causes substantial degradation in spatial resolution for objects near the periphery of the breast. In this work, a framework for computing and incorporating an accurate system matrix into iterative reconstruction is presented in an effort to reduce spatial resolution degradation towards the periphery of the breast. The GATE Monte Carlo Simulation software was utilized to accurately model the system matrix for a breast PET system. A strategy for increasing the count statistics in the system matrix computation and for reducing the system element storage space was used by calculating only a subset of matrix elements and then estimating the rest of the elements by using the geometric symmetry of the cylindrical scanner. To implement this strategy, polar voxel basis functions were used to represent the object, resulting in a block-circulant system matrix. Simulation studies using a breast PET scanner model with ring geometry demonstrated improved contrast at 45% reduced noise level and 1.5 to 3 times resolution performance improvement when compared to MLEM reconstruction using a simple line-integral model. The GATE based system matrix reconstruction technique promises to improve resolution and noise performance and reduce image distortion at FOV periphery compared to line-integral based system matrix reconstruction.
Modelling Random Coincidences in Positron Emission Tomography by Using Singles and Prompts: A Comparison Study.
Oliver, Josep F; Rafecas, M
Random coincidences degrade the image in Positron Emission Tomography, PET. To compensate for their degradation effects, the rate of random coincidences should be estimated. Under certain circumstances, current estimation methods fail to provide accurate results. We propose a novel method, "Singles-Prompts" (SP), that includes the information conveyed by prompt coincidences and models the pile-up. The SP method has the same structure than the well-known "Singles Rate" (SR) approach. Hence, SP can straightforwardly replace SR. In this work, the SP method has been extensively assessed and compared to two conventional methods, SR and the delayed window (DW) method, in a preclinical PET scenario using Monte-Carlo simulations. SP offers accurate estimates for the randoms rates, while SR and DW tend to overestimate the rates (∼10%, and 5%, respectively). With pile-up, the SP method is more robust than SR (but less than DW). At the image level, the contrast is overestimated in SR-corrected images, +16%, while SP produces the correct value. Spill-over is slightly reduced using SP instead of SR. The DW images values are similar to those of SP except for low-statistic scenarios, where DW behaves as if randoms were not compensated for. In particular, the contrast is reduced, -16%. In general, the better estimations of SP translate into better image quality. PMID:27603143
An interior-point method for total variation regularized positron emission tomography image reconstruction
NASA Astrophysics Data System (ADS)
Bai, Bing
There has been a lot of work on total variation (TV) regularized tomographic image reconstruction recently. Many of them use gradient-based optimization algorithms with a differentiable approximation of the TV functional. In this paper we apply TV regularization in Positron Emission Tomography (PET) image reconstruction. We reconstruct the PET image in a Bayesian framework, using Poisson noise model and TV prior functional. The original optimization problem is transformed to an equivalent problem with inequality constraints by adding auxiliary variables. Then we use an interior point method with logarithmic barrier functions to solve the constrained optimization problem. In this method, a series of points approaching the solution from inside the feasible region are found by solving a sequence of subproblems characterized by an increasing positive parameter. We use preconditioned conjugate gradient (PCG) algorithm to solve the subproblems directly. The nonnegativity constraint is enforced by bend line search. The exact expression of the TV functional is used in our calculations. Simulation results show that the algorithm converges fast and the convergence is insensitive to the values of the regularization and reconstruction parameters.
Modelling Random Coincidences in Positron Emission Tomography by Using Singles and Prompts: A Comparison Study
Random coincidences degrade the image in Positron Emission Tomography, PET. To compensate for their degradation effects, the rate of random coincidences should be estimated. Under certain circumstances, current estimation methods fail to provide accurate results. We propose a novel method, "Singles–Prompts" (SP), that includes the information conveyed by prompt coincidences and models the pile–up. The SP method has the same structure than the well-known "Singles Rate" (SR) approach. Hence, SP can straightforwardly replace SR. In this work, the SP method has been extensively assessed and compared to two conventional methods, SR and the delayed window (DW) method, in a preclinical PET scenario using Monte–Carlo simulations. SP offers accurate estimates for the randoms rates, while SR and DW tend to overestimate the rates (∼10%, and 5%, respectively). With pile-up, the SP method is more robust than SR (but less than DW). At the image level, the contrast is overestimated in SR-corrected images, +16%, while SP produces the correct value. Spill–over is slightly reduced using SP instead of SR. The DW images values are similar to those of SP except for low-statistic scenarios, where DW behaves as if randoms were not compensated for. In particular, the contrast is reduced, −16%. In general, the better estimations of SP translate into better image quality. PMID:27603143
Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients
Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang
Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259
Correlation of physical parameters during radiochemical synthesis of (18)F positron emission tomography radiopharmaceuticals.
Tiwari, Anjani K; Varshney, Raunak; Kaushik, Aruna; Datta, Anupama; Singh, Lokendra; Mishra, Anil K
Positron emission tomography is a highly specialized imaging technique using short-lived radiolabel substances to produce extremely high resolution images of the body's biological function. The (18)F(-) ion is produced via the (18)O(p,n)(18)F reaction using a silver target cell filled with 1.4 mL of enriched [(18)O] water. On a typical run, the target is irradiated for 45 minutes with 16.5 MeV protons (on target) and an average beam current of 5-45 mA. When the same reaction takes place with [(16)O] water [(13)N] Ammonia is produced as the primary product by the abstraction of hydrogen from water. This study investigated the physical parameters of medical cyclotron during the radiochemical process with induced radioactivity flux and mutual correlation of physical parameters for 16.5 MeV medical cyclotron at the INMAS Delhi, India. It is observed that by getting farther from the target, the relative number of low-energy neutrons increases while the overall flux of neutrons decreases. This is due to multiple scattering of high-energy neutrons in the walls and eventually absorption of low-energy neutrons. The other parameters are also linked with each other which are correlatable.
An investigation into positron emission tomography contouring methods across two treatment planning systems
Young, Tony; Som, Seu; Sathiakumar, Chithradevi; Holloway, Lois
Positron emission tomography (PET) imaging has been used to provide additional information regarding patient tumor location, size, and staging for radiotherapy treatment planning purposes. This additional information reduces interobserver variability and produces more consistent contouring. It is well recognized that different contouring methodology for PET data results in different contoured volumes. The goal of this study was to compare the difference in PET contouring methods for 2 different treatment planning systems using a phantom dataset and a series of patient datasets. Contouring methodology was compared on the ADAC Pinnacle Treatment Planning System and the CMS XiO Treatment Planning System. Contours were completed on the phantom and patient datasets using a number of PET contouring methods—the standardized uptake value 2.5 method, 30%, 40%, and 50% of the maximum uptake method and the signal to background ratio method. Differences of >15% were observed for PET-contoured volumes between the different treatment planning systems for the same data and the same PET contouring methodology. Contoured volume differences between treatment planning systems were caused by differences in data formatting and display and the different contouring tools available. Differences in treatment planning system as well as contouring methodology should be considered carefully in dose-volume contouring and reporting, especially between centers that may use different treatment planning systems or those that have several different treatment planning systems.
Cognitive processes and cerebral cortical fundi: findings from positron-emission tomography studies.
Markowitsch, H J; Tulving, E
Positron-emission tomography (PET) studies of regional cerebral blood flow have provided evidence relevant to localization of cognitive functions. The critical loci identified in these studies are typically described in terms of macroanatomically labeled cortical and subcortical regions. We report the results of a meta-analysis of localization of changes in blood flow, based on nearly 1000 cerebral cortical peaks of activity obtained from groups of subjects in 30 PET studies. The results showed that, on average, 47% of these peaks were localized within the fundus regions of cortical sulci. This is an unexpectedly high proportion because fundal regions compose < 8% of the cortical mantle. Further analysis suggested a coarse correlation between the extent of fundal activation observed in different studies and the estimated cognitive complexity of the tasks used in the studies. These findings are potentially interesting because (i) the preponderance of fundal activation has implications for the interpretation of the PET data, (ii) they suggest that cortical sulcal and fundal regions may play a distinctive role in higher cognitive processing, or (iii) both of the above. PMID:7937984
Metabolizer in vivo of fullerenes and metallofullerenes by positron emission tomography.
Li, Juan; Yang, Wenjiang; Cui, Rongli; Wang, Dongliang; Chang, Yanan; Gu, Weihong; Yin, Wenyan; Bai, Xue; Chen, Kui; Xia, Lin; Geng, Huan; Xing, Gengmei
Fullerenes (C60) and metallofullerenes (Gd@C82) have similar chemical structure, but the bio-effects of both fullerene-based materials are distinct in vivo. Tracking organic carbon-based materials such as C60 and Gd@C82 is difficult in vivo due to the high content of carbon element in the living tissues themselves. In this study, the biodistribution and metabolism of fullerenes (C60 and Gd@C82) radiolabeled with (64)Cu were observed by positron emission tomography (PET). (64)Cu-C60 and (64)Cu-Gd@C82 were prepared using 1, 4, 7, 10-tetrakis (carbamoylmethyl)-1, 4, 7, 10-tetra-azacyclodo-decanes grafted on carbon cages as a chelator for (64)Cu, and were obtained rapidly with high radiochemical yield (≥90%). The new radio-conjugates were evaluated in vivo in the normal mouse model and tissue distribution by small animal PET/CT imaging and histology was carried out. The PET imaging, the biodistribution and the excretion of C60 and Gd@C82 indicated that C60 samples have higher blood retention and lower renal clearance than the Gd@C82 samples in vivo and suggested that the differences in metabolism and distribution in vivo were caused by the structural differences of the groups on the fullerene cages though there is chemical similarity between C60 and Gd@C82.
Evoked Potentials and Neuropsychological Tests Validate Positron Emission Topography (PET) Brain Metabolism in Cognitively Impaired Patients
Braverman, Eric R.; Blum, Kenneth; Damle, Uma J.; Kerner, Mallory; Dushaj, Kristina; Oscar-Berman, Marlene
Fluorodeoxyglucose (FDG) Positron Emission Topography (PET) brain hypometabolism (HM) correlates with diminished cognitive capacity and risk of developing dementia. However, because clinical utility of PET is limited by cost, we sought to determine whether a less costly electrophysiological measure, the P300 evoked potential, in combination with neuropsychological test performance, would validate PET HM in neuropsychiatric patients. We found that patients with amnestic and non-amnestic cognitive impairment and HM (n = 43) evidenced significantly reduced P300 amplitudes, delayed latencies, and neuropsychological deficits, compared to patients with normal brain metabolism (NM; n = 187). Data from patients with missing cognitive test scores (n = 57) were removed from the final sample, and logistic regression modeling was performed on the modified sample (n = 173, p = .000004). The logistic regression modeling, based on P300 and neuropsychological measures, was used to validate membership in the HM vs. NM groups. It showed classification validation in 13/25 HM subjects (52.0%) and in 125/148 NM subjects (84.5%), correlating with total classification accuracy of 79.8%. In this paper, abnormal P300 evoked potentials coupled with cognitive test impairment validates brain metabolism and mild/moderate cognitive impairment (MCI). To this end, we cautiously propose incorporating electrophysiological and neuropsychological assessments as cost-effective brain metabolism and MCI indicators in primary care. Final interpretation of these results must await required additional studies confirming these interesting results. PMID:23526928
Imaging Brain Metabolism and Pathology in Alzheimer's Disease with Positron Emission Tomography
Shokouhi, S; Claassen, D; Riddle, WR
Current Positron Emission Tomography (PET) biomarkers for Alzheimer's disease (AD) assess either neuronal function, or associated pathological features of this common neurodegenerative disease. The most widely accepted clinical PET tool for AD is 18-fluorodeoxyglucose PET (FDG-PET), which measures cerebral metabolic glucose utilization rate (CMRglc). FDG-PET is a marker of synaptic activity, neuronal function, and neuronal metabolic activity. AD is characterized by a distinct pattern of hypometabolism, as seen with the FDG images. This pattern can show variability across different subjects and is present before a patient is demented, specifically in amnestic mild cognitive impairment a clinical diagnosis defined as an intermediate state from normal aging to dementia. In addition to FDG PET, novel PET approaches assess known pathological hallmarks of AD including extracellular amyloid-beta plaques (Aβ) and intracellular neurofibrillary tangles composed of tau fibrils. Already, amyloid PET imaging is a tool that allows in vivo imaging of extracellular beta-amyloid levels. Efforts to bring tau imaging into clinical use continue, but this approach is hampered by the intracellular nature of tau protein deposition, subsequent weak radiotracer binding, and low image contrast. Several new candidate probes for tau-specific PET imaging are currently available but have not found their way into broad clinical applications. This study gives an overview of the most recent PET-based neuroimaging techniques for AD. We place special emphasis on PET data analysis and interpretation techniques, as well as radiochemistry for imaging metabolism and assessing Aβ and tau pathology. PMID:25343059
Utility of positron emission tomography-magnetic resonance imaging in musculoskeletal imaging
Chaudhry, Ammar A; Gul, Maryam; Gould, Elaine; Teng, Mathew; Baker, Kevin; Matthews, Robert
Differentiation between neoplastic and nonneoplastic conditions magnetic resonance imaging (MRI) has established itself as one of the key clinical tools in evaluation of musculoskeletal pathology. However, MRI still has several key limitations which require supplemental information from additional modalities to complete evaluation of various disorders. This has led to the development hybrid positron emission tomography (PET)-MRI which is rapidly evolving to address key clinical questions by using the morphological strengths of MRI and functional information of PET imaging. In this article, we aim to review physical principles and techniques of PET-MRI and discuss clinical utility of functional information obtained from PET imaging and structural information obtained from MRI imaging for the evaluation of musculoskeletal pathology. More specifically, this review highlights the role of PET-MRI in musculoskeletal oncology including initial diagnosis and staging, treatment planning and post-treatment follow-up. Also we will review utility of PET-MRI in evaluating musculoskeletal infections (especially in the immunocompromised and diabetics) and inflammatory condition. Additionally, common pitfalls of PET-MRI will be addressed. PMID:27027320
FPGA-Based Front-End Electronics for Positron Emission Tomography
Haselman, Michael; DeWitt, Don; McDougald, Wendy; Lewellen, Thomas K.; Miyaoka, Robert; Hauck, Scott
Modern Field Programmable Gate Arrays (FPGAs) are capable of performing complex discrete signal processing algorithms with clock rates above 100MHz. This combined with FPGA's low expense, ease of use, and selected dedicated hardware make them an ideal technology for a data acquisition system for positron emission tomography (PET) scanners. Our laboratory is producing a high-resolution, small-animal PET scanner that utilizes FPGAs as the core of the front-end electronics. For this next generation scanner, functions that are typically performed in dedicated circuits, or offline, are being migrated to the FPGA. This will not only simplify the electronics, but the features of modern FPGAs can be utilizes to add significant signal processing power to produce higher resolution images. In this paper two such processes, sub-clock rate pulse timing and event localization, will be discussed in detail. We show that timing performed in the FPGA can achieve a resolution that is suitable for small-animal scanners, and will outperform the analog version given a low enough sampling period for the ADC. We will also show that the position of events in the scanner can be determined in real time using a statistical positioning based algorithm. PMID:21961085
Attenuation correction with region growing method used in the positron emission mammography imaging system
NASA Astrophysics Data System (ADS)
Gu, Xiao-Yue; Li, Lin; Yin, Peng-Fei; Yun, Ming-Kai; Chai, Pei; Huang, Xian-Chao; Sun, Xiao-Li; Wei, Long
The Positron Emission Mammography imaging system (PEMi) provides a novel nuclear diagnosis method dedicated for breast imaging. With a better resolution than whole body PET, PEMi can detect millimeter-sized breast tumors. To address the requirement of semi-quantitative analysis with a radiotracer concentration map of the breast, a new attenuation correction method based on a three-dimensional seeded region growing image segmentation (3DSRG-AC) method has been developed. The method gives a 3D connected region as the segmentation result instead of image slices. The continuity property of the segmentation result makes this new method free of activity variation of breast tissues. The threshold value chosen is the key process for the segmentation method. The first valley in the grey level histogram of the reconstruction image is set as the lower threshold, which works well in clinical application. Results show that attenuation correction for PEMi improves the image quality and the quantitative accuracy of radioactivity distribution determination. Attenuation correction also improves the probability of detecting small and early breast tumors. Supported by Knowledge Innovation Project of The Chinese Academy of Sciences (KJCX2-EW-N06)
Stochastic modelling of physiologic processes with radiotracers and positron emission tomography
Rescigno, A.; Lambrecht, R.M.; Duncan, C.C.
The compartment model, so often used in nuclear medicine and in pharmacokinetics, is formed by a set of linear differential equations of order one with constant coefficients; its validity depends upon the hypothesis that the system described contains a finite number of components, and that each component is homogeneous. These hypotheses exclude the presence of diffusion and of age-dependent processes, or in general of transport of a non-Markovian nature. The fact that frequently the experimental data agree with this model does not necessarily prove the model is appropriate, but only that it is flexible. In addition to the consistency with the experimental data, an obvious conceptual requirement of the model is that its parameters could be interpreted in terms of perceivable physical properties. All this considered, it will be demonstrated that the experimental data can be examined in terms of a model making a minimum number of assumptions and giving the best physical interpretations to the parameters involved. By way of example, a high resolution positron emission tomograph will be used to determine the successive moments describing the blood circulation through different sections of the brain. Whereever the relative moments form a geometric progression, the circulation in that section follows the rules of a perfect compartment; if this is not the case, the analytical method described can be used to describe the behavior of a tracer particle in the part of the organ. (ERB)
Photo-Detectors for Time of Flight Positron Emission Tomography (ToF-PET)
Spanoudaki, Virginia Ch.; Levin⋆, Craig S.
We present the most recent advances in photo-detector design employed in time of flight positron emission tomography (ToF-PET). PET is a molecular imaging modality that collects pairs of coincident (temporally correlated) annihilation photons emitted from the patient body. The annihilation photon detector typically comprises a scintillation crystal coupled to a fast photo-detector. ToF information provides better localization of the annihilation event along the line formed by each detector pair, resulting in an overall improvement in signal to noise ratio (SNR) of the reconstructed image. Apart from the demand for high luminosity and fast decay time of the scintillation crystal, proper design and selection of the photo-detector and methods for arrival time pick-off are a prerequisite for achieving excellent time resolution required for ToF-PET. We review the two types of photo-detectors used in ToF-PET: photomultiplier tubes (PMTs) and silicon photo-multipliers (SiPMs) with a special focus on SiPMs. PMID:22163482
Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET)/MRI for Lung Cancer Staging.
Ohno, Yoshiharu; Koyama, Hisanobu; Lee, Ho Yun; Yoshikawa, Takeshi; Sugimura, Kazuro
Tumor, lymph node, and metastasis (TNM) classification of lung cancer is typically performed with the TNM staging system, as recommended by the Union Internationale Contre le Cancer (UICC), the American Joint Committee on Cancer (AJCC), and the International Association for the Study of Lung Cancer (IASLC). Radiologic examinations for TNM staging of lung cancer patients include computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG-PET), and FDG-PET combined with CT (FDG-PET/CT) and are used for pretherapeutic assessments. Recent technical advances in MR systems, application of fast and parallel imaging and/or introduction of new MR techniques, and utilization of contrast media have markedly improved the diagnostic utility of MRI in this setting. In addition, FDG-PET can be combined or fused with MRI (PET/MRI) for clinical practice. This review article will focus on these recent advances in MRI as well as on PET/MRI for lung cancer staging, in addition to a discussion of their potential and limitations for routine clinical practice in comparison with other modalities such as CT, FDG-PET, and PET/CT.
Visual form discrimination from color or motion cues: functional anatomy by positron emission tomography.
Gulyás, B; Heywood, C A; Popplewell, D A; Roland, P E; Cowey, A
To explore the extent to which various cortical functional pathways are involved in processing and analyzing different types of information that yield the same perceptual entity, we mapped anatomical structures in the human brain participating in the discrimination of visual forms mediated either by motion or color cues. Changes in regional cerebral blood flow were measured in 10 young male volunteers with positron emission tomography and with [15O]butanol. During the measurements, the subjects performed four visual discrimination tasks (form-from-motion, motion alone, form-from-color, and color alone discrimination). The individual regional cerebral blood flow images were standardized in shape and size with the help of a computerized brain atlas. Subtraction images were determined and averaged across data from all subjects. The resulting images were analyzed for statistically significant changes between specific and reference tasks. The discrimination of form by means of motion cues activated functional fields bilaterally in the inferior and lateral occipital gyri, in the lingual, anterior cingulate, middle frontal and orbitofrontal gyri, and in the left fusiform and right inferior temporal gyri. Form discrimination by color cues resulted in activation bilaterally in the inferior temporal, lateral occipital, and orbitofrontal gyri, the left precuneus and intraparietal sulcus, and the right precentral gyrus. The regions engaged in the two kinds of form discrimination did not overlap, demonstrating that differences in visual forms mediated by color or motion cues are processed and analyzed by disparate networks of functional fields in human cerebral cortex. Images PMID:7937927
Positron Emission Tomography to Assess the Outcome of Intraportal Islet Transplantation.
Eriksson, Olof; Selvaraju, Ramkumar; Eich, Torsten; Willny, Mariam; Brismar, Torkel B; Carlbom, Lina; Ahlström, Håkan; Tufvesson, Gunnar; Lundgren, Torbjörn; Korsgren, Olle
No imaging methodology currently exists to monitor viable islet mass after clinical intraportal islet transplantation. We investigated the potential of the endocrine positron emission tomography (PET) marker [(11)C]5-hydroxytryptophan ([(11)C]5-HTP) for this purpose. In a preclinical proof-of-concept study, the ex vivo and in vivo [(11)C]5-HTP signal was compared with the number of islets transplanted in rats. In a clinical study, human subjects with an intraportal islet graft (n = 8) underwent two [(11)C]5-HTP PET and MRI examinations 8 months apart. The tracer concentration in the liver as a whole, or in defined hotspots, was correlated to measurements of islet graft function. In rat, hepatic uptake of [(11)C]5-HTP correlated with the number of transplanted islets. In human subjects, uptake in hepatic hotspots showed a correlation with metabolic assessments of islet function. Change in hotspot standardized uptake value (SUV) predicted loss of graft function in one subject, whereas hotspot SUV was unchanged in subjects with stable graft function. The endocrine marker [(11)C]5-HTP thus shows a correlation between hepatic uptake and transplanted islet function and promise as a tool for noninvasive detection of viable islets. The evaluation procedure described can be used as a benchmark for novel agents targeting intraportally transplanted islets. PMID:27325286
The role of positron emission tomography in the detection of pancreatic disease
Syrota, A.; Duquesnoy, N.; Paraf, A.; Kellershohn, C.
Positron emission tomography (PET) was used to assess possible pancreatic disease in 100 patients. Following injection of 10-15 mCi (370-740 MBq) of 11C-L-methionine, 4-12 transverse sections 2 cm thick were obtained. In 85 patients with a definite diagnosis (45 normal, 9 acute pancreatitis, 18 chronic pancreatitis, and 13 cancer), PET showed a sensitivity of 85.0%, a specificity of 97.8%, and an accuracy of 91.8%, higher than with transmission computed tomography (CT) or ultrasonography, despite relatively low spatial resolution; this can be explained by the fact that exocrine pancreatic function was altered prior to morphological change. In 22 normal subjects, 0.011 +/- 0.003% (mean +/- S.D). of injected 11C was found in 1 ml of liver tissue and 0.015 +/- 0.005% in 1 ml of pancreatic tissue; the pancreas-to-liver concentration ratio was 1.3 +/- 0.4. Hepatic 11C concentration was identical in the four groups of patients. Pancreatic uptake of 11C-L-methionine was significantly lower in patients with chronic pancreatitis (n . 13) and pancreatic carcinoma (n . 10) (p less than 0.001); however, it was not possible to distinguish cancer from chronic pancreatitis because the same functional alteration occurred in both.
The role of positron emission tomography in the detection of pancreatic disease
Syrota, A.; Duquesnoy, N.; Paraf, A.; Kellershohn, C.
Positron emission tomography (PET) was used to assess possible pancreatic disease in 100 patients. Following injection of 10-15 mCi (370-740 MBq) of /sup 11/C-L-methionine, 4-12 transverse sections 2 cm thick were obtained. In 85 patients with a definite diagnosis (45 normal, 9 acute pancreatitis, 18 chronic pancreatitis, and 13 cancer), PET showed a sensitivity of 85.0%, a specificity of 97.8%, and an accuracy of 91.8%, higher than with transmission computed tomography (CT) or ultrasonography, despite relatively low spatial resolution; this can be explained by the fact that exocrine pancreatic function was altered prior to morphological change. In 22 normal subjects, 0.011 +/- 0.003% (mean +/- S.D.) of injected /sup 11/C was found in 1 ml of liver tissue and 0.015 +/- 0.005% in 1 ml of pancreatic tissue; the pancreas-to-liver concentration ratio was 1.3 +/- 0.4. Hepatic /sup 11/C concentration was identical in the four groups of patients. Pancreatic uptake of /sup 11/C-L-methionine was significantly lower in patients with chronic pancreatitis (n = 13) and pancreatic carcinoma (n = 10) (p <0.001); however, it was not possible to distinguish cancer from chronic pancreatitis because the same functional alteration occurred in both.
The role of pallidal serotonergic function in Parkinson's disease dyskinesias: a positron emission tomography study.
Smith, Ruben; Wu, Kit; Hart, Thomas; Loane, Clare; Brooks, David J; Björklund, Anders; Odin, Per; Piccini, Paola; Politis, Marios
We have investigated the role of globus pallidus (GP) serotonergic terminals in the development of levodopa-induced dyskinesias (LIDs) in Parkinson's disease (PD). We studied 12 PD patients without LIDs, 12 PD patients with LIDs, and 12 healthy control subjects. We used (11)C-DASB positron emission tomography (PET), a marker of serotonin transporter availability, and (11)C-raclopride PET to measure changes in synaptic dopamine levels following levodopa administration. PD patients without LIDs showed a significant reduction of GP serotonin transporter binding compared with healthy controls although this was within the normal range in PD patients with LIDs. Levels of GP serotonin transporter binding correlated positively with severity of dyskinesias. (11)C-raclopride PET detected a significant rise in GP synaptic dopamine levels of patients with LIDs after a levodopa challenge but not in patients with a stable response. Our findings indicate that LIDs in PD are associated with higher GP serotonergic function. This increased serotonin function may result in further dysregulation of thalamocortical signals and so promote the expression of dyskinesias. PMID:25649022
[Positron emission tomography (PET): a useful tool for the assessment of cardiac metabolism].
Alexánderson, Erick; Gómez-Martín, Diana; Benito, Israel; Ruíz-Ramírez, Leonel; Ricalde, Alejandro; Meave, Aloha
Under normal conditions, myocardial metabolism is based on the oxidation of fatty acids and in a lesser extent carbohydrates. Cardiac function depends upon an adequate supplement of adenosine triphosphate (ATP) by these substrates. However, the main source of energy is susceptible to change upon a various physiologic (exercise) as well as pathologic (ischemia-reperfusion) conditions. Recently, carnitine has gained attention as a modulator of fatty acids and carbohydrates metabolism by means of modifying intramitochondrial Acetyl-CoA/CoA ratio. Disturbances in fatty acids and carbohydrates metabolism in the myocardium have been associated with cardiovascular diseases (chronic ischemic disease, ventricular hypertrophy and dilated cardiomyopathy). The evaluation of cardiac metabolism attains great value regarding diagnosis, treatment and prognosis of these diseases. Currently, positron emission tomography (PET) is one of the preferred methods to evaluate cardiac energy metabolism in clinical practice. In PET images the tracers most commonly used are 11C-palmitate, 11C-acetate y 18Fluoro-2-deoxyglucose (FDG), the first two are employed to assess fatty acids oxidation and FDG is used to evaluate carbohydrates metabolism. PMID:15559875
Clinical Utility of Positron Emission Tomography Magnetic Resonance Imaging (PET-MRI) in Gastrointestinal Cancers
Matthews, Robert; Choi, Minsig
Anatomic imaging utilizing both CT (computed tomography) and MRI (magnetic resonance imaging) limits the assessment of cancer metastases in lymph nodes and distant organs while functional imaging like PET (positron emission tomography) scan has its limitation in spatial resolution capacity. Hybrid imaging utilizing PET-CT and PET-MRI are novel imaging modalities that are changing the current landscape in cancer diagnosis, staging, and treatment response. MRI has shown to have higher sensitivity in soft tissue, head and neck pathology, and pelvic disease, as well as, detecting small metastases in the liver and bone compared to CT. Combining MRI with PET allows for detection of metastases that may have been missed with current imaging modalities. In this review, we will examine the clinical utility of FDG PET-MRI in the diagnosis and staging of gastrointestinal cancers with focus on esophageal, stomach, colorectal, and pancreatic cancers. We will also explore its role in treatment response and future directions associated with it. PMID:27618106
Pulmonary malignant melanoma with distant metastasis assessed by positron emission tomography-computed tomography.
Kim, So Ri; Yoon, Ha-Yong; Jin, Gong Yong; Choe, Yeong Hun; Park, Seung Yong; Lee, Yong Chul
Melanoma is a cutaneous malignant neoplasm of melanocytes. Primary malignant melanoma (MM) of the lung is very rare. Although previous reports have described the radiologic features of pulmonary MM, its rarity means that many factors are unknown. Thus, radiologic diagnosis is very difficult. Furthermore, there is little information regarding diagnostic application and/or the usefulness of [(18)F]-fluorine-2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (FDG-PET-CT) for primary pulmonary MM. A 69-year-old patient with a productive cough lasting three weeks was admitted to our hospital. Chest CT showed a large single mass with a multi-lobulated margin and homogeneous enhancement in the right upper lobe, which was subsequently diagnosed as a primary pulmonary MM with multiple metastases. On PET-CT images, the pulmonary mass and multiple bone lesions showed very increased uptakes of FDG. Considering that pulmonary metastasis from a mucocutaneous melanoma is the main differential diagnosis of primary pulmonary MM, systemic assessment of the whole body is more important than for other types of lung malignancies. This report introduces PET-CT as a useful diagnostic modality for pulmonary MM, especially in cases of distant multiple metastases. PMID:27385996
Positron emission tomography / computerized tomography evaluation of primary Hodgkin's disease of liver.
Gota, V S; Purandare, N C; Gujral, S; Shah, S; Nair, R; Rangarajan, V
Occurrence of primary Hodgkin's lymphoma (PHL) of the liver is extremely rare. We report on a case of a 60-year-old male who presented with liver mass and B-symptomatology. Hepatoma or hepatic metastasis from a gastrointestinal primary was initially suspected. Tumor markers like AFP, CEA, Total PSA, and CA-19.9 were within normal limits. Positron Emission Tomography / Computerized Tomography (PET/CT) revealed a large hepatic lesion and a nodal mass in the porta hepatis. A liver biopsy was consistent with Hodgkin's lymphoma. There was complete regression of the hepatic lesion and evidence of shrinkage of the nodal mass following four cycles of chemotherapy. 18F Fluro -de-oxy Glucose (FDG) PET / CT in this case helped in establishing a primary hepatic lymphoma by demonstrating the absence of pathologically hypermetabolic foci in any other nodes or organs. PET / CT scan is a useful adjunct to conventional imaging and histopathology, not only to establish the initial diagnosis, but also to monitor treatment response in PHL.
Eyeblink conditioning in unmedicated schizophrenia patients: A positron emission tomography study
Parker, Krystal L.; Andreasen, Nancy C.; Liu, Dawei; Freeman, John H.; O'Leary, Daniel S.
Previous studies suggest that patients with schizophrenia exhibit dysfunctions in a widely distributed circuit—the cortico-cerebellar-thalamic-cortical circuit, or CCTCC—and that this may explain the multiple cognitive deficits observed in the disorder. This study uses positron emission tomography (PET) with O15 H2O to measure regional cerebral blood flow (rCBF) in response to a classic test of cerebellar function, the associative learning that occurs during eyeblink conditioning, in a sample of 20 unmedicated schizophrenia patients and 20 closely matched healthy controls. The PET paradigm examined three phases of acquisition and extinction (early, middle and late). The patients displayed impaired behavioral performance during both acquisition and extinction. The imaging data indicate that, compared to the control subjects, the patients displayed decreases in rCBF in all three components of the CCTCC during both acquisition and extinction. Specifically, patients had less rCBF in the middle and medial frontal lobes, anterior cerebellar lobules I/V and VI, as well as the thalamus during acquisition and although similar areas were found in the frontal lobe, ipsilateral cerebellar lobule IX showed consistently less activity in patients during extinction. Thus this study provides additional support for the hypothesis that patients with schizophrenia have a cognitive dysmetria—an inability to smoothly coordinate many different types of mental activity—that affects even a very basic cognitive task that taps into associative learning. PMID:24090512
Neural correlates of malingering in mild traumatic brain injury: A positron emission tomography study.
Spadoni, Andrea D; Kosheleva, Elena; Buchsbaum, Monte S; Simmons, Alan N
The detection of malingering in cognitive performance is a challenge in clinical and legal environments. Neuroimaging may provide an objective method to determine the source of failure on tests of symptom validity. Participants comprised 45 combat veterans, 31 with mild traumatic brain injury (mTBI), not seeking medical or legal compensation, who completed the Tombaugh Test of Memory Malingering (TOMM) and a positron emission tomography (PET) scan. Based on TOMM performance (i.e., less than 45 of 50 total correct, suggesting suboptimal effort or malingering), subjects were separated into poor TOMM score (PT; n=10) and good TOMM score (GT; n=35) groups. Voxel-based multiple regression analysis with Group (GT/PT) predicting uptake of fluorodeoxyglucose revealed decreased brain metabolism in the ventromedial prefrontal cortex of poor performers. The current findings may suggest that poor TOMM performance in those with combat trauma and mTBI may be related to ventromedial prefrontal cortical dysfunction. These findings have important implications for the disentanglement of feigned versus actual memory impairment, where the latter may be secondary to neural mechanisms not consistent with forgetting or deception.
A promising new mechanism of ionizing radiation detection for positron emission tomography: modulation of optical properties
NASA Astrophysics Data System (ADS)
Tao, Li; Daghighian, Henry M.; Levin, Craig S.
Using conventional scintillation detection, the fundamental limit in positron emission tomography (PET) time resolution is strongly dependent on the inherent temporal variances generated during the scintillation process, yielding an intrinsic physical limit for the coincidence time resolution of around 100 ps. On the other hand, modulation mechanisms of the optical properties of a material exploited in the optical telecommunications industry can be orders of magnitude faster. In this paper we borrow from the concept of optics pump-probe measurement to for the first time study whether ionizing radiation can produce modulations of optical properties, which can be utilized as a novel method for radiation detection. We show that a refractive index modulation of approximately 5× {{10}-6} is induced by interactions in a cadmium telluride (CdTe) crystal from a 511 keV photon source. Furthermore, using additional radionuclide sources, we show that the amplitude of the optical modulation signal varies linearly with both the detected event rate and average photon energy of the radiation source.
Iterative reconstruction using a Monte Carlo based system transfer matrix for dedicated breast positron emission tomography
NASA Astrophysics Data System (ADS)
Saha, Krishnendu; Straus, Kenneth J.; Chen, Yu.; Glick, Stephen J.
To maximize sensitivity, it is desirable that ring Positron Emission Tomography (PET) systems dedicated for imaging the breast have a small bore. Unfortunately, due to parallax error this causes substantial degradation in spatial resolution for objects near the periphery of the breast. In this work, a framework for computing and incorporating an accurate system matrix into iterative reconstruction is presented in an effort to reduce spatial resolution degradation towards the periphery of the breast. The GATE Monte Carlo Simulation software was utilized to accurately model the system matrix for a breast PET system. A strategy for increasing the count statistics in the system matrix computation and for reducing the system element storage space was used by calculating only a subset of matrix elements and then estimating the rest of the elements by using the geometric symmetry of the cylindrical scanner. To implement this strategy, polar voxel basis functions were used to represent the object, resulting in a block-circulant system matrix. Simulation studies using a breast PET scanner model with ring geometry demonstrated improved contrast at 45% reduced noise level and 1.5 to 3 times resolution performance improvement when compared to MLEM reconstruction using a simple line-integral model. The GATE based system matrix reconstruction technique promises to improve resolution and noise performance and reduce image distortion at FOV periphery compared to line-integral based system matrix reconstruction.
Metabolizer in vivo of fullerenes and metallofullerenes by positron emission tomography
NASA Astrophysics Data System (ADS)
Li, Juan; Yang, Wenjiang; Cui, Rongli; Wang, Dongliang; Chang, Yanan; Gu, Weihong; Yin, Wenyan; Bai, Xue; Chen, Kui; Xia, Lin; Geng, Huan; Xing, Gengmei
Fullerenes (C60) and metallofullerenes (Gd@C82) have similar chemical structure, but the bio-effects of both fullerene-based materials are distinct in vivo. Tracking organic carbon-based materials such as C60 and Gd@C82 is difficult in vivo due to the high content of carbon element in the living tissues themselves. In this study, the biodistribution and metabolism of fullerenes (C60 and Gd@C82) radiolabeled with 64Cu were observed by positron emission tomography (PET). 64Cu-C60 and 64Cu-Gd@C82 were prepared using 1, 4, 7, 10-tetrakis (carbamoylmethyl)-1, 4, 7, 10-tetra-azacyclodo-decanes grafted on carbon cages as a chelator for 64Cu, and were obtained rapidly with high radiochemical yield (≥90%). The new radio-conjugates were evaluated in vivo in the normal mouse model and tissue distribution by small animal PET/CT imaging and histology was carried out. The PET imaging, the biodistribution and the excretion of C60 and Gd@C82 indicated that C60 samples have higher blood retention and lower renal clearance than the Gd@C82 samples in vivo and suggested that the differences in metabolism and distribution in vivo were caused by the structural differences of the groups on the fullerene cages though there is chemical similarity between C60 and Gd@C82.
18F-Fluorodeoxyglucose Positron Emission Tomography/CT Scanning in Diagnosing Vascular Prosthetic Graft Infection
Saleem, Ben R.; Pol, Robert A.; Slart, Riemer H. J. A.; Reijnen, Michel M. P. J.; Zeebregts, Clark J.
Vascular prosthetic graft infection (VPGI) is a severe complication after vascular surgery. CT-scan is considered the diagnostic tool of choice in advanced VPGI. The incidence of a false-negative result using CT is relatively high, especially in the presence of low-grade infections. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scanning has been suggested as an alternative for the diagnosis and assessment of infectious processes. Hybrid 18F-FDG PET/CT has established the role of 18F-FDG PET for the assessment of suspected VPGI, providing accurate anatomic localization of the site of infection. However, there are no clear guidelines for the interpretation of the uptake patterns of 18F-FDG as clinical tool for VPGI. Based on the available literature it is suggested that a linear, diffuse, and homogeneous uptake should not be regarded as an infection whereas focal or heterogeneous uptake with a projection over the vessel on CT is highly suggestive of infection. Nevertheless, 18F-FDG PET and 18F-FDG PET/CT can play an important role in the detection of VPGI and monitoring response to treatment. However an accurate uptake and pattern recognition is warranted and cut-off uptake values and patterns need to be standardized before considering the technique to be the new standard. PMID:25210712
Low background high efficiency radiocesium detection system based on positron emission tomography technology
Yamamoto, Seiichi; Ogata, Yoshimune
After the 2011 nuclear power plant accident at Fukushima, radiocesium contamination in food became a serious concern in Japan. However, low background and high efficiency radiocesium detectors are expensive and huge, including semiconductor germanium detectors. To solve this problem, we developed a radiocesium detector by employing positron emission tomography (PET) technology. Because {sup 134}Cs emits two gamma photons (795 and 605 keV) within 5 ps, they can selectively be measured with coincidence. Such major environmental gamma photons as {sup 40}K (1.46 MeV) are single photon emitters and a coincidence measurement reduces the detection limit of radiocesium detectors. We arranged eight sets of Bi{sub 4}Ge{sub 3}O{sub 12} (BGO) scintillation detectors in double rings (four for each ring) and measured the coincidence between these detectors using PET data acquisition system. A 50 × 50 × 30 mm BGO was optically coupled to a 2 in. square photomultiplier tube (PMT). By measuring the coincidence, we eliminated most single gamma photons from the energy distribution and only detected those from {sup 134}Cs at an average efficiency of 12%. The minimum detectable concentration of the system for the 100 s acquisition time is less than half of the food monitor requirements in Japan (25 Bq/kg). These results show that the developed radiocesium detector based on PET technology is promising to detect low level radiocesium.
Amyloid and metabolic positron emission tomography imaging of cognitively normal adults with Alzheimer's parents.
Mosconi, Lisa; Rinne, Juha O; Tsui, Wai H; Murray, John; Li, Yi; Glodzik, Lidia; McHugh, Pauline; Williams, Schantel; Cummings, Megan; Pirraglia, Elizabeth; Goldsmith, Stanley J; Vallabhajosula, Shankar; Scheinin, Noora; Viljanen, Tapio; Någren, Kjell; de Leon, Mony J
This study examines the relationship between fibrillar beta-amyloid (Aβ) deposition and reduced glucose metabolism, a proxy for neuronal dysfunction, in cognitively normal (NL) individuals with a parent affected by late-onset Alzheimer's disease (AD). Forty-seven 40-80-year-old NL received positron emission tomography (PET) with (11)C-Pittsburgh compound B (PiB) and 18F-fluoro-2-deoxy-d-glucose (FDG). These included 19 NL with a maternal history (MH), 12 NL with a paternal history (PH), and 16 NL with negative family history of AD (NH). Automated regions of interest, statistical parametric mapping, voxel-wise intermodality correlations, and logistic regressions were used to examine cerebral-to-cerebellar PiB and FDG standardized uptake value ratios across groups. The MH group showed higher PiB retention and lower metabolism in AD regions compared with NH and PH, which were negatively correlated in posterior cingulate, frontal, and parieto-temporal regions (Pearson r ≤ -0.57, p ≤ 0.05). No correlations were observed in NH and PH. The combination of Aβ deposition and metabolism yielded accuracy ≥ 69% for MH vs. NH and ≥ 71% for MH vs. PH, with relative risk = 1.9-5.1 (p values < 0.005). NL individuals with AD-affected mothers show co-occurring Aβ increases and hypometabolism in AD-vulnerable regions, suggesting an increased risk for AD.
Neural correlates of sensorimotor gating: a metabolic positron emission tomography study in awake rats.
Rohleder, Cathrin; Jung, Fabienne; Mertgens, Hanna; Wiedermann, Dirk; Sué, Michael; Neumaier, Bernd; Graf, Rudolf; Leweke, F Markus; Endepols, Heike
Impaired sensorimotor gating occurs in neuropsychiatric disorders such as schizophrenia and can be measured using the prepulse inhibition (PPI) paradigm of the acoustic startle response. This assay is frequently used to validate animal models of neuropsychiatric disorders and to explore the therapeutic potential of new drugs. The underlying neural network of PPI has been extensively studied with invasive methods and genetic modifications. However, its relevance for healthy untreated animals and the functional interplay between startle- and PPI-related areas during a PPI session is so far unknown. Therefore, we studied awake rats in a PPI paradigm, startle control and background noise control, combined with behavioral [(18)F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Subtractive analyses between conditions were used to identify brain regions involved in startle and PPI processing in well-hearing Black hooded rats. For correlative analysis with regard to the amount of PPI we also included hearing-impaired Lister hooded rats that startled more often, because their hearing threshold was just below the lowest prepulses. Metabolic imaging showed that the brain areas proposed for startle and PPI mediation are active during PPI paradigms in healthy untreated rats. More importantly, we show for the first time that the whole PPI modulation network is active during "passive" PPI sessions, where no selective attention to prepulse or startle stimulus is required. We conclude that this reflects ongoing monitoring of stimulus significance and constant adjustment of sensorimotor gating.
18Fluorodeoxyglucose positron emission tomography studies in presumed Alzheimer cases, including 13 serial scans.
McGeer, E G; Peppard, R P; McGeer, P L; Tuokko, H; Crockett, D; Parks, R; Akiyama, H; Calne, D B; Beattie, B L; Harrop, R
Positron emission tomographic (PET) data on local cerebral metabolic rates for glucose (LCMR) are reported for 32 regions of interest (ROI)s in cross-sectional studies on 57 patients with clinically diagnosed Alzheimer's disease (AD) and 20 neurologically normal controls, and in serial studies on 13 of the AD cases, including a familial, young-onset case where the diagnosis has been confirmed at autopsy. Extensive psychological testing was done on all the AD cases. Almost all cortical regions showed a significant decline in LCMR with age in the control subjects. There were the expected cortical metabolic deficits in AD and the serial studies showed a general increase in such deficits over time in 12 of the 13 cases. The regions showing the greatest declines with time in serial studies are the same as those showing the most severe deficiencies in cross-sectional studies. The young-onset case did not show a greater rate of metabolic decline than many of the older cases studied. Results on individual psychological tests tended to correlate with metabolic rates in multiple, rather than single, cortical regions, suggesting intact neuronal networks are required for good performance. The correlations with cortical metabolic activity found were of a sign indicating that the higher the metabolic rates and the better the left:right asymmetry index, the better was the performance.
(18)F-Labeling of Mannan for Inflammation Research with Positron Emission Tomography.
Li, Xiang-Guo; Hagert, Cecilia; Siitonen, Riikka; Virtanen, Helena; Sareila, Outi; Liljenbäck, Heidi; Tuisku, Jouni; Knuuti, Juhani; Bergman, Jörgen; Holmdahl, Rikard; Roivainen, Anne
Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice, and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 ((18)F) and study the (18)F-labeled mannan in vitro and in vivo with positron emission tomography (PET). Accordingly, mannan has been transformed into (18)F-fluoromannan with (18)F-bicyclo[6.1.0]nonyne. In mouse aorta, the binding of [(18)F]fluoromannan to the atherosclerotic lesions was clearly visualized and was significantly higher compared to blocking assays (P < 0.001) or healthy mouse aorta (P < 0.001). In healthy rats the [(18)F]fluoromannan radioactivity accumulated largely in the macrophage-rich organs such as liver, spleen, and bone marrow and the excess excreted in urine. Furthermore, the corresponding (19)F-labeled mannan has been used to induce psoriasis and psoriatic arthritis in mice, which indicates that the biological function of mannan is preserved after the chemical modifications. PMID:27660685
Initial characterization of a BGO-photodiode detector for high resolution positron emission tomography
Derenzo, S.E.
Spatial resolution in positron emission tomography is currently limited by the resolution of the detectors. This work presents the initial characterization of a detector design using small bismuth germanate (BGO) crystals individually coupled to silicon photodiodes (SPDs) for crystal identification, and coupled in groups to phototubes (PMTs) for coincidence timing. A 3 mm x 3 mm x 3 mm BGO crystal coupled only to an SPD can achieve a 511 keV photopeak resolution of 8.7% FWHM at -150/sup 0/C, using a pulse peaking time of 10 ..mu..s. When two 3 mm x 3 mm x 15 mm BGO crystals are coupled individually to SPDs and also coupled to a common 14 mm diam PMT, the SPDs detect the 511 keV photopeak with a resolution of 30% FWHM at -76/sup 0/C. In coincidence with an opposing 3 mm wide BGO crystal, the SPDs are able to identify the crystal of interaction with good signal-to-noise ratio, and the detector pair resolution is 2 mm FWHM. 32 references, 7 figures, 3 tables.
New approaches to gastric cancer staging: Beyond endoscopic ultrasound, computed tomography and positron emission tomography
Yoon, Hyuk; Lee, Dong Ho
Currently, there is no single gold standard modality for staging of gastric cancer and several methods have been used complementarily in the each clinical situation. To make up for the shortcomings of conventional modalities such as endoscopic ultrasound, computed tomography and 18F-fluoro-2-deoxyglucose positron emission tomography, numerous attempts with new approaches have been made for gastric cancer staging. For T staging, magnifying endoscopy with narrow-band was evaluated to differentiate mucosal cancer from submucosal cancer. Single/double contrast-enhanced ultrasound and diffusion-weighted magnetic resonance imaging were also tried to improve diagnostic accuracy of gastric cancer. For intraoperative staging with sentinel node mapping, indocyanine green infrared and fluorescence imaging was introduced. In addition, to detect micrometastasis, real-time reverse transcription-polymerase chain reaction system with multiple markers was studied. Staging laparoscopy using 5-aminolevulinic acid-mediated photodynamic diagnosis and percutaneous diagnostic peritoneal lavage were also evaluated. However, most studies reporting new staging methods is preliminary and further studies for validation in clinical practice are needed. In this mini-review, we discuss new progress in gastric cancer staging. Especially, we focus on new diagnostic approach to gastric cancer staging beyond the conventional modalities and briefly review the remarkable clinical results of the studies published over the past three years. PMID:25320516
The use of positron emission tomography imaging in the management of patients with ischemic cardiomyopathy.
Maddahi, J; Blitz, A; Phelps, M; Laks, H
Rational management of patients with CAD and poor left ventricular function relies on proper identification of the subgroup at high risk and those who have the highest potential of benefiting from a particular type of treatment. It is now well recognized that patients with CAD and left ventricular dysfunction have a high but variable mortality rate while receiving medical therapy. Many of these patients who have intractable heart failure are considered candidates for cardiac transplantation. Despite favorable survival after cardiac transplantation, this procedure cannot be performed in 90% of the heart failure patients who are potentially eligible because of the shortage of donor hearts. Cardiac transplantation is also an expensive procedure. Perfusion-FDG metabolism PET imaging has become the gold-standard noninvasive imaging method to identify the presence and extent of hibernating myocardium. Positron emission tomography accurately predicts recovery of regional and global left ventricular dysfunction after revascularization. In patients with poor left ventricular function, the PET pattern of perfusion metabolism mismatch is also predictive of improvement in heart failure symptoms and survival benefit after myocardial revascularization. These data suggest that a rational approach may be developed for cost-effective management of patients with CAD and poor left ventricular function.
Exploring the nature of atheroma and cardiovascular inflammation in vivo using positron emission tomography (PET)
Positron emission tomography (PET) has become widely established in oncology. Subsequently, a whole new "toolbox" of tracers have become available to look at different aspects of cancer cell function and dysfunction, including cell protein production, DNA synthesis, hypoxia and angiogenesis. In the past 5 years, these tools have been used increasingly to look at the other great killer of the developed world: cardiovascular disease. For example, inflammation of the unstable plaque can be imaged with 18-fludeoxyglucose (18F-FDG), and this uptake can be quantified to show the effect that statins have in reducing inflammation and explains how these drugs can reduce the risk of stroke. 18F-FDG has also become established in diagnosing and monitoring large-vessel vasculitis and has now entered routine practice. Other agents such as gallium-68 (68Ga) octreotide have been shown to identify vascular inflammation possibly more specifically than 18F-FDG. Hypoxia within the plaque can be imaged with 18F-fluoromisonidazole and resulting angiogenesis with 18F-RGD peptides. Active calcification such as that found in unstable atheromatous plaques can be imaged with 18F-NaF. PET imaging enables us to understand the mechanisms by which cardiovascular disease, including atheroma, leads to morbidity and death and thus increases the chance of finding new and effective treatments. PMID:26110339
Positron Emission Tomography (PET) Quantification of GABAA Receptors in the Brain of Fragile X Patients
Van der Aa, Nathalie; Goffin, Karolien; Koole, Michel; Porke, Kathleen; Van De Velde, Marc; Rooms, Liesbeth; Van Paesschen, Wim; Van Esch, Hilde; Van Laere, Koen; Kooy, R. Frank
Over the last several years, evidence has accumulated that the GABAA receptor is compromised in animal models for fragile X syndrome (FXS), a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABAA receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET) and [11C]flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABAA receptors. We measured regional GABAA receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABAA receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABAA receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABAA receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABAA receptor is a potential target for rational pharmacological treatment of fragile X syndrome. PMID:26222316
Pulmonary malignant melanoma with distant metastasis assessed by positron emission tomography‐computed tomography
Yoon, Ha‐Yong; Jin, Gong Yong; Choe, Yeong Hun; Park, Seung Yong
Abstract Melanoma is a cutaneous malignant neoplasm of melanocytes. Primary malignant melanoma (MM) of the lung is very rare. Although previous reports have described the radiologic features of pulmonary MM, its rarity means that many factors are unknown. Thus, radiologic diagnosis is very difficult. Furthermore, there is little information regarding diagnostic application and/or the usefulness of [18F]‐fluorine‐2‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography‐computed tomography (FDG‐PET‐CT) for primary pulmonary MM. A 69‐year‐old patient with a productive cough lasting three weeks was admitted to our hospital. Chest CT showed a large single mass with a multi‐lobulated margin and homogeneous enhancement in the right upper lobe, which was subsequently diagnosed as a primary pulmonary MM with multiple metastases. On PET‐CT images, the pulmonary mass and multiple bone lesions showed very increased uptakes of FDG. Considering that pulmonary metastasis from a mucocutaneous melanoma is the main differential diagnosis of primary pulmonary MM, systemic assessment of the whole body is more important than for other types of lung malignancies. This report introduces PET‐CT as a useful diagnostic modality for pulmonary MM, especially in cases of distant multiple metastases. PMID:27385996
Assessment of Cancer-Associated Biomarkers by Positron Emission Tomography: Advances and Challenges
Collier, T. Lee; Lecomte, Roger; McCarthy, Timothy J.; Meikle, Steve; Ruth, Thomas J.; Scopinaro, Francesco; Signore, Alberto; Van Brocklin, Henry; Van de Wiele, Christophe; Waterhouse, Rikki N.
Positron emission tomography (PET) provides a powerful means to non-invasively image and quantify protein expression and biochemical changes in living subjects at nano- and picomolar levels. As the field of molecular imaging develops, and as advances in the biochemistry, pharmacology, therapeutics, and molecular biology of disease are made, there is a corresponding increase in the number of clinically relevant, novel disease-associated biomarkers that are brought to the attention of those developing imaging probes for PET. In addition, due to the high specificity of the PET radiotracers being developed, there is a demand for PET cameras with higher sensitivity and resolution. This manuscript reviews advances over the past five years in clinical and pre-clinical PET instrumentation and in new PET probes and imaging methods associated with the latest trends in the molecular imaging of cancer. Included in the PET tracer review is a description of new radioligands for steroid receptors, growth factor receptors, receptor tyrosine kinases, sigma receptors, tumor-associated enzymes, gene reporter probes, markers for tumor hypoxia and metabolism, and sites associated with angiogenesis and cellular proliferation. The use of PET imaging in drug development, including the monitoring of cancer chemotherapy, also is discussed. PMID:14646039
Hydrogen-bond promoted nucleophilic fluorination: concept, mechanism and applications in positron emission tomography.
Lee, Ji-Woong; Oliveira, Maria Teresa; Jang, Hyeong Bin; Lee, Sungyul; Chi, Dae Yoon; Kim, Dong Wook; Song, Choong Eui
Due to the tremendous interest in carbon-fluorine bond-forming reactions, research efforts in this area have been dedicated to the development of facile processes to synthesize small fluorine-containing organic molecules. Among others, PET (Positron Emission Tomography) is one of the most important applications of fluorine chemistry. Recognizing the specific requirements of PET processes, some groups have focused on fluorination reactions using alkali metal fluorides, particularly through SN2-type reactions. However, a common "misconception" about the role of protic solvents and hydrogen bonding interactions in this class of reactions has hampered the employment of these excellent promoters. Herein, we would like to review recent discoveries in this context, showing straightforward nucleophilic fluorination reactions using alkali metal fluorides promoted by protic solvents. Simultaneous dual activation of reacting partners by intermolecular hydrogen bonding and the enhancement of the "effective fluoride nucleophilicity", which is Nature's biocatalytic approach with the fluorinase enzyme, are the key to this unprecedentedly successful nucleophilic fluorination. PMID:27264160
Regional Cerebral Glucose Metabolism in Novelty Seeking and Antisocial Personality: A Positron Emission Tomography Study.
Park, So Hyeon; Park, Hyun Soo; Kim, Sang Eun
Novelty seeking (NS) and antisocial personality (ASP) are commonly exhibited by those who suffer from addictions, such as substance abuse. NS has been suggested to be a fundamental aspect of ASP. To investigate the neurobiological substrate of NS and ASP, we tested the relationship between regional cerebral glucose metabolism and the level of NS, determining the differences between individuals with and without ASP. Seventy-two healthy adults (43 males, mean age±SD=38.8±16.6 years, range=20~70 years; 29 females, 44.2±20.1 years, range=19~72 years) underwent resting-state brain positron emission tomography (PET) 40 minutes after (18)F-fluorodeoxyglucose (FDG) injection. Within 10 days of the FDG PET study, participants completed Cloninger's 240-item Temperament and Character Inventory (TCI) to determine NS scores. Participants with and without ASP were grouped according to their TCI profiles. Statistical parametric mapping analysis was performed using the FDG PET and TCI profile data. NS scores positively correlated with metabolism in the left anterior cingulate gyrus and the insula on both sides of the brain and negatively correlated with metabolism in the right pallidum and putamen. Participants with ASP showed differences in cerebral glucose metabolism across various cortical and subcortical regions, mainly in the frontal and prefrontal areas. These data demonstrate altered regional cerebral glucose metabolism in individuals with NS and ASP and inform our understanding of the neurobiological substrates of problematic behaviors and personality disorders. PMID:27574485
Speech disorders in olivopontocerebellar atrophy correlate with positron emission tomography findings
Kluin, K.J.; Gilman, S.; Markel, D.S.; Koeppe, R.A.; Rosenthal, G.; Junck, L.
We compared the severity of ataxic and spastic dysarthria with local cerebral metabolic rates for glucose (lCMRGlc) in 30 patients with olivopontocerebellar atrophy (OPCA). Perceptual analysis was used to examine the speech disorders, and rating scales were devised to quantitate the degree of ataxia and spasticity in the speech of each patient. lCMRGlc was measured with /sup 18/F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). PET studies revealed marked hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem of OPCA patients compared with 30 control subjects. With data normalized to the cerebral cortex, a significant inverse correlation was found between the severity of ataxia in speech and the lCMRGlc within the cerebellar vermis, cerebellar hemispheres, and brainstem, but not within the thalamus. No significant correlation was found between the severity of spasticity in speech and lCMRGlc in any of these structures. The findings support the view that the severity of ataxia in speech in OPCA is related to the functional activity of the cerebellum and its connections in the brainstem.
Clinical Utility of Positron Emission Tomography Magnetic Resonance Imaging (PET-MRI) in Gastrointestinal Cancers.
Matthews, Robert; Choi, Minsig
Anatomic imaging utilizing both CT (computed tomography) and MRI (magnetic resonance imaging) limits the assessment of cancer metastases in lymph nodes and distant organs while functional imaging like PET (positron emission tomography) scan has its limitation in spatial resolution capacity. Hybrid imaging utilizing PET-CT and PET-MRI are novel imaging modalities that are changing the current landscape in cancer diagnosis, staging, and treatment response. MRI has shown to have higher sensitivity in soft tissue, head and neck pathology, and pelvic disease, as well as, detecting small metastases in the liver and bone compared to CT. Combining MRI with PET allows for detection of metastases that may have been missed with current imaging modalities. In this review, we will examine the clinical utility of FDG PET-MRI in the diagnosis and staging of gastrointestinal cancers with focus on esophageal, stomach, colorectal, and pancreatic cancers. We will also explore its role in treatment response and future directions associated with it. PMID:27618106
A fast rebinning algorithm for 3D positron emission tomography using John's equation
NASA Astrophysics Data System (ADS)
Defrise, Michel; Liu, Xuan
Volume imaging in positron emission tomography (PET) requires the inversion of the three-dimensional (3D) x-ray transform. The usual solution to this problem is based on 3D filtered-backprojection (FBP), but is slow. Alternative methods have been proposed which factor the 3D data into independent 2D data sets corresponding to the 2D Radon transforms of a stack of parallel slices. Each slice is then reconstructed using 2D FBP. These so-called rebinning methods are numerically efficient but are approximate. In this paper a new exact rebinning method is derived by exploiting the fact that the 3D x-ray transform of a function is the solution to the second-order partial differential equation first studied by John. The method is proposed for two sampling schemes, one corresponding to a pair of infinite plane detectors and another one corresponding to a cylindrical multi-ring PET scanner. The new FORE-J algorithm has been implemented for this latter geometry and was compared with the approximate Fourier rebinning algorithm FORE and with another exact rebinning algorithm, FOREX. Results with simulated data demonstrate a significant improvement in accuracy compared to FORE, while the reconstruction time is doubled. Compared to FOREX, the FORE-J algorithm is slightly less accurate but more than three times faster.
A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects
Zavaleta, Cristina L.; Nielsen, Carsten H.; Mesangeau, Christophe; Vuppala, Pradeep K.; Chan, Carmel; Avery, Bonnie A.; Fishback, James A.; Matsumoto, Rae R.; Gambhir, Sanjiv S.; McCurdy, Christopher R.; Chin, Frederick T.
Sigma-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([18F]FTC-146, [18F]13). [18F]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 ± 1.2 Ci/Amol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [18F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pre treatment with 1 mg/kg haloperidol (2), non radioactive 13, or BD1047 (18) reduced the binding of [18F]13 in the brain at 60 min by 80%, 82% and 81% respectively, suggesting that [18F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [18F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects. PMID:22853801
Positron emission tomography (PET) studies of dopaminergic/cholinergic interactions in the baboon brain
Dewey, S.L.; Brodie, J.D.; Fowler, J.S.; MacGregor, R.R.; Schlyer, D.J.; King, P.T.; Alexoff, D.L.; Volkow, N.D.; Shiue, C.Y.; Wolf, A.P. )
Interactions between the dopaminergic D2 receptor system and the muscarinic cholinergic system in the corpus striatum of adult female baboons (Papio anubis) were examined using positron emission tomography (PET) combined with (18F)N-methylspiroperidol (( 18F)NMSP) (to probe D2 receptor availability) and (N-11C-methyl)benztropine (to probe muscarinic cholinergic receptor availability). Pretreatment with benztropine, a long-lasting anticholinergic drug, bilaterally reduced the incorporation of radioactivity in the corpus striatum but did not alter that observed in the cerebellum or the rate of metabolism of (18F)NMSP in plasma. Pretreatment with unlabelled NMSP, a potent dopaminergic antagonist, reduced the incorporation of (N-11C-methyl)benztropine in all brain regions, with the greatest effect being in the corpus striatum greater than cortex greater than thalamus greater than cerebellum, but did not alter the rate of metabolism of the labelled benztropine in the plasma. These reductions in the incorporation of either (18F)NMSP or (N-11C-methyl)benztropine exceeded the normal variation in tracer incorporation in repeated studies in the same animal. This study demonstrates that PET can be used as a tool for investigating interactions between neurochemically different yet functionally linked neurotransmitters systems in vivo and provides insight into the consequences of multiple pharmacologic administration.
Effect of Harderian adenectomy on the statistical analyses of mouse brain imaging using positron emission tomography.
Kim, Minsoo; Woo, Sang-Keun; Yu, Jung Woo; Lee, Yong Jin; Kim, Kyeong Min; Kang, Joo Hyun; Eom, Kidong; Nahm, Sang-Soep
Positron emission tomography (PET) using 2-deoxy-2-[(18)F] fluoro-D-glucose (FDG) as a radioactive tracer is a useful technique for in vivo brain imaging. However, the anatomical and physiological features of the Harderian gland limit the use of FDG-PET imaging in the mouse brain. The gland shows strong FDG uptake, which in turn results in distorted PET images of the frontal brain region. The purpose of this study was to determine if a simple surgical procedure to remove the Harderian gland prior to PET imaging of mouse brains could reduce or eliminate FDG uptake. Measurement of FDG uptake in unilaterally adenectomized mice showed that the radioactive signal emitted from the intact Harderian gland distorts frontal brain region images. Spatial parametric measurement analysis demonstrated that the presence of the Harderian gland could prevent accurate assessment of brain PET imaging. Bilateral Harderian adenectomy efficiently eliminated unwanted radioactive signal spillover into the frontal brain region beginning on postoperative Day 10. Harderian adenectomy did not cause any post-operative complications during the experimental period. These findings demonstrate the benefits of performing a Harderian adenectomy prior to PET imaging of mouse brains.
Whole body positron emission tomography imaging of simian immunodeficiency virus-infected rhesus macaques.
Scharko, A M; Perlman, S B; Hinds PW2nd; Hanson, J M; Uno, H; Pauza, C D
Pathogenesis of simian immunodeficiency virus (SIV) infection in rhesus macaques begins with acute viremia and then progresses to a distributed infection in the solid lymphoid tissues, which is followed by a process of cellular destruction leading to terminal disease and death. Blood and tissue specimens show the progress of infection at the cellular level but do not reveal the pattern of infection and host responses occurring throughout the body. The purpose of this investigation was to determine whether positron emission tomography (PET) imaging with intravenous 2-18F-2-deoxyglucose (FDG) could identify activated lymphoid tissues in a living animal and whether this pattern would reflect the extent of SIV infection. PET images from SIV-infected animals were distinguishable from uninfected controls and revealed a pattern consistent with widespread lymphoid tissue activation. Significant FDG accumulation in colon along with mesenteric and ileocaecal lymph nodes was found in SIV infection, especially during terminal disease stages. Areas of elevated FDG uptake in the PET images were correlated with productive SIV infection using in situ hybridization as a test for virus replication. PET-FDG images of SIV-infected animals correlated sites of virus replication with high FDG accumulation. These data show that the method can be used to evaluate the distribution and activity of infected tissues in a living animal without biopsy. Fewer tissues had high FDG uptake in terminal animals than midstage animals, and both were clearly distinguishable from uninfected animal scans. Images Fig. 1 Fig. 2 Fig. 3 PMID:8692831
Fluorine-18 fluorodeoxyglucose positron emission tomography imaging of T-lymphoblastic lymphoma patients
Park, Jong Hoon; Pahk, Kisoo; Kim, Sungeun; Lim, Sang Moo; Cheon, Gi Jeong; Park, Yeon Hee; Lee, Seung-Sook; Choe, Jae Gol
The purpose of the present study was to evaluate the fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings in patients with T-lymphoblastic lymphoma (T-LBL). In total, 9 patients with histopathologically confirmed T-LBL were included in the study. Bone marrow (BM) involvement and leukemic transformation (LT) were evaluated through iliac crest marrow biopsy and peripheral blood blast count. FDG-PET scans were performed at the initial pre-treatment point. Two experienced nuclear medicine physicians evaluated the FDG-PET images by visual analysis and using the maximum standardized uptake values (SUVmax) of the malignant lesions. Overall, 8 out 9 patients presented with BM involvement; 7 showed LT, while 1 showed BM involvement without LT. All involved T-LBL lesions were FDG-avid with variable uptake. The mean SUVmax was 6.4±3.3. T-LBL patients with BM involvement showed diffuse or nodular marrow uptake. In addition, all the patients with LT showed diffuse marrow FDG activity. However, the patient with BM involvement but no LT showed nodular FDG uptake in the marrow. In conclusion, the present study indicates that it is possible to use FDG-PET for the evaluation of the disease extent of T-LBL. Furthermore, the imaging technique could provide a diagnostic clue for determining BM involvement or LT. PMID:27446482
Novel electro-optical coupling technique for magnetic resonance-compatible positron emission tomography detectors.
Olcott, Peter D; Peng, Hao; Levin, Craig S
A new magnetic resonance imaging (MRI)-compatible positron emission tomography (PET) detector design is being developed that uses electro-optical coupling to bring the amplitude and arrival time information of high-speed PET detector scintillation pulses out of an MRI system. The electro-optical coupling technology consists of a magnetically insensitive photodetector output signal connected to a nonmagnetic vertical cavity surface emitting laser (VCSEL) diode that is coupled to a multimode optical fiber. This scheme essentially acts as an optical wire with no influence on the MRI system. To test the feasibility of this approach, a lutetium-yttrium oxyorthosilicate crystal coupled to a single pixel of a solid-state photomultiplier array was placed in coincidence with a lutetium oxyorthosilicate crystal coupled to a fast photomultiplier tube with both the new nonmagnetic VCSEL coupling and the standard coaxial cable signal transmission scheme. No significant change was observed in 511 keV photopeak energy resolution and coincidence time resolution. This electro-optical coupling technology enables an MRI-compatible PET block detector to have a reduced electromagnetic footprint compared with the signal transmission schemes deployed in the current MRI/PET designs.
Positron emission mammography with tomographic acquisition using dual planar detectors: initial evaluations
Mark F Smith; Raymond R Raylman; Stan Majewski; Andrew G Weisenberger
Positron emission mammography (PEM) with tomographic acquisition using dual planar detectors rotating about the breast can obtain complete angular sampling and has the potential to improve activity estimation compared with PEM using stationary detectors. PEM tomography (PEMT) was compared with stationary PEM for point source and compressed breast phantom studies performed with a compact dual detector system. The acquisition geometries were appropriate for the target application of PEM guidance of stereotactic core biopsy. Images were reconstructed with a three-dimensional iterative maximum likelihood expectation maximization algorithm. PEMT eliminated blurring normal to the detectors seen with stationary PEM. Depth of interaction effects distorted the shape of the point spread functions for PEMT as the angular range from normal incidence of lines of response used in image reconstruction increased. Streak artifacts in PEMT for large detector rotation increments led to the development of an expression for the maximum rotation increment that maintains complete angular sampling. Studies with a compressed breast phantom were used to investigate contrast and signal-to-noise ratio (SNR) trade-offs for different sized spherical tumor models. PEMT and PEM both had advantages depending on lesion size and detector separation. The most appropriate acquisition method for specific detection or quantitation tasks requires additional investigation.
Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function
Berent, S.; Giordani, B.; Lehtinen, S.; Markel, D.; Penney, J.B.; Buchtel, H.A.; Starosta-Rubinstein, S.; Hichwa, R.; Young, A.B.
Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of /sup 18/F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation.
Injectable silver nanosensors: in vivo dosimetry for external beam radiotherapy using positron emission tomography.
Christensen, A N; Rydhög, J S; Søndergaard, R V; Andresen, T L; Holm, S; Munck Af Rosenschöld, P; Conradsen, K; Jølck, R I
Development of safe and efficient radiotherapy routines requires quantification of the delivered absorbed dose to the cancer tissue in individual patients. In vivo dosimetry can provide accurate information about the absorbed dose delivered during treatment. In the current study, a novel silver-nanosensor formulation based on poly(vinylpyrrolidinone)-coated silver nanoparticles formulated in a gelation matrix composed of sucrose acetate isobutyrate has been developed for use as an in vivo dosimeter for external beam radiotherapy. In situ photonuclear reactions trigger the formation of radioactive (106)Ag, which enables post treatment verification of the delivered dose using positron emission tomography imaging. The silver-nanosensor was investigated in a tissue equivalent thorax phantom using clinical settings and workflow for both standard fractionated radiotherapy (2 Gy) and stereotactic radiotherapy (10- and 22 Gy) in a high-energy beam setting (18 MV). The developed silver-nanosensor provided high radiopacity on the planning CT-scans sufficient for patient positioning in image-guided radiotherapy and provided dosimetric information about the absorbed dose with a 10% and 8% standard deviation for the stereotactic regimens, 10 and 22 Gy, respectively. PMID:27174233
Regional Cerebral Glucose Metabolism in Novelty Seeking and Antisocial Personality: A Positron Emission Tomography Study
Park, So Hyeon; Park, Hyun Soo
Novelty seeking (NS) and antisocial personality (ASP) are commonly exhibited by those who suffer from addictions, such as substance abuse. NS has been suggested to be a fundamental aspect of ASP. To investigate the neurobiological substrate of NS and ASP, we tested the relationship between regional cerebral glucose metabolism and the level of NS, determining the differences between individuals with and without ASP. Seventy-two healthy adults (43 males, mean age±SD=38.8±16.6 years, range=20~70 years; 29 females, 44.2±20.1 years, range=19~72 years) underwent resting-state brain positron emission tomography (PET) 40 minutes after 18F-fluorodeoxyglucose (FDG) injection. Within 10 days of the FDG PET study, participants completed Cloninger's 240-item Temperament and Character Inventory (TCI) to determine NS scores. Participants with and without ASP were grouped according to their TCI profiles. Statistical parametric mapping analysis was performed using the FDG PET and TCI profile data. NS scores positively correlated with metabolism in the left anterior cingulate gyrus and the insula on both sides of the brain and negatively correlated with metabolism in the right pallidum and putamen. Participants with ASP showed differences in cerebral glucose metabolism across various cortical and subcortical regions, mainly in the frontal and prefrontal areas. These data demonstrate altered regional cerebral glucose metabolism in individuals with NS and ASP and inform our understanding of the neurobiological substrates of problematic behaviors and personality disorders. PMID:27574485
Functional reorganisation of memory after traumatic brain injury: a study with H2150 positron emission tomography
Levine, B; Cabeza, R; McIntosh, A; Black, S; Grady, C; Stuss, D
Objective: To study the effects of moderate to severe traumatic brain injury (TBI) on the functional neuroanatomy supporting memory retrieval. Methods: Subjects were six patients who had sustained a moderate to severe TBI about four years before scanning and had since made a good recovery. Eleven healthy young adults matched to the patients for age and education served as controls. An established H2150 positron emission tomography paradigm was used to elicit brain activations in response to memory retrieval. TBI patients' patterns of brain activation were compared statistically with those of control subjects. Both group and individual case data were analysed. Results: Both TBI patients and controls engaged frontal, temporal, and parietal regions known to be involved in memory retrieval, yet the TBI patients showed relative increases in frontal, anterior cingulate, and occipital activity. The hemispheric asymmetry characteristic of controls was attenuated in patients with TBI. Reduced activation was noted in the right dorsomedial thalamus. Although local aspects of this pattern were affected by the presence of focal lesions and performance differences, the overall pattern was reliable across patients and comparable to functional neuroimaging results reported for normal aging, Alzheimer's disease, and other patients with TBI. Conclusions: The TBI patients performed memory tasks using altered functional neuroanatomical networks. These changes are probably the result of diffuse axonal injury and may reflect either cortical disinhibition attributable to disconnection or compensation for inefficient mnemonic processes. PMID:12122177
The metabolic landscape of cortico-basal ganglionic degeneration: regional asymmetries studied with positron emission tomography.
Eidelberg, D; Dhawan, V; Moeller, J R; Sidtis, J J; Ginos, J Z; Strother, S C; Cederbaum, J; Greene, P; Fahn, S; Powers, J M
Regional metabolic rate for glucose (rCMRGlc) was estimated using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) in five patients (four men, one woman; mean age 68; mean disease duration 2.4 years) with clinical findings consistent with the syndrome of cortico-basal ganglionic degeneration (CBGD). Left-right rCMRGlc asymmetry, (L-R)/(L + R) x 100, was calculated for 13 grey matter regions and compared with regional metabolic data from 18 normal volunteers and nine patients with asymmetrical Parkinson's disease (PD). In the CBGD group mean metabolic asymmetry values in the thalamus, inferior parietal lobule and hippocampus were greater than those measured in normal control subjects and patients with asymmetrical PD (p less than 0.02). Parietal lobe asymmetry of 5% or more was evident in all CBGD patients, whereas in PD patients and normal controls, all regional asymmetry measures were less than 5% in absolute value. Measures of frontal, parietal and hemispheric metabolic asymmetry were found to be positively correlated with asymmetries in thalamic rCMRGlc (p less than 0.05). The presence of cortico-thalamic metabolic asymmetry is consistent with the focal neuropathological changes reported in CBGD brains. Our findings suggest that metabolic asymmetries detected with FDG/PET may support a diagnosis of CBGD in life. Images PMID:1744638
Assessing tumor hypoxia by positron emission tomography with Cu-ATSM.
Holland, J P; Lewis, J S; Dehdashti, F
For the last several decades, hypoxia has been recognized to be one of the key factors in tumor aggression and an important impediment to local and distant control of malignant tumors. In addition, hypoxia is a major cause of failure of both radiation therapy and chemotherapy. It has been shown that hypoxia is an independent negative prognostic factor for patient outcome in various solid tumors. Clinical studies using polarographic oxygen electrodes, as a tool for measuring hypoxia, were the first to demonstrate the presence of hypoxia in human tumors and its association with poor prognosis. However, this method is invasive and has technical limitations that prevent its routine clinical use. Over the years, imaging as a noninvasive method has attracted a lot of attention and several radiotracers have been developed for noninvasive evaluation of hypoxia. One of the most promising radiotracers is the copper(II) complex of diacetyl-2,3-bis(N(4)-methyl-3-thiosemicarbazonato) ligand (Cu-ATSM) for imaging with positron emission tomography. In this review, the preclinical evaluation of Cu-ATSM as well as its clinical value in several solid tumors will be discussed.
Positron emission tomography to assess hypoxia and perfusion in lung cancer
Verwer, Eline E; Boellaard, Ronald; van der Veldt, Astrid AM
In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed. PMID:25493221
Neural correlates of sensorimotor gating: a metabolic positron emission tomography study in awake rats
Rohleder, Cathrin; Jung, Fabienne; Mertgens, Hanna; Wiedermann, Dirk; Sué, Michael; Neumaier, Bernd; Graf, Rudolf; Leweke, F. Markus; Endepols, Heike
Impaired sensorimotor gating occurs in neuropsychiatric disorders such as schizophrenia and can be measured using the prepulse inhibition (PPI) paradigm of the acoustic startle response. This assay is frequently used to validate animal models of neuropsychiatric disorders and to explore the therapeutic potential of new drugs. The underlying neural network of PPI has been extensively studied with invasive methods and genetic modifications. However, its relevance for healthy untreated animals and the functional interplay between startle- and PPI-related areas during a PPI session is so far unknown. Therefore, we studied awake rats in a PPI paradigm, startle control and background noise control, combined with behavioral [18F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Subtractive analyses between conditions were used to identify brain regions involved in startle and PPI processing in well-hearing Black hooded rats. For correlative analysis with regard to the amount of PPI we also included hearing-impaired Lister hooded rats that startled more often, because their hearing threshold was just below the lowest prepulses. Metabolic imaging showed that the brain areas proposed for startle and PPI mediation are active during PPI paradigms in healthy untreated rats. More importantly, we show for the first time that the whole PPI modulation network is active during "passive" PPI sessions, where no selective attention to prepulse or startle stimulus is required. We conclude that this reflects ongoing monitoring of stimulus significance and constant adjustment of sensorimotor gating. PMID:24904330
Evaluation of Glucose Uptake in Normal and Cancer Cell Lines by Positron Emission Tomography.
Maddalena, Francesca; Lettini, Giacomo; Gallicchio, Rosj; Sisinni, Lorenza; Simeon, Vittorio; Nardelli, Anna; Venetucci, Angela Assunta; Storto, Giovanni; Landriscina, Matteo
To date, there is no definitive demonstration of the utility of positron emission tomography (PET) in studying glucose metabolism in cultured cell lines. Thus, this study was designed to compare PET to more standardized methods for the quantitative assessment of glucose uptake in nontransformed and transformed living cells and to validate PET for metabolic studies in vitro. Human colon and breast carcinoma cell lines and mouse embryo fibroblasts were evaluated for [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake by PET and autoradiography and 2-deoxyglucose (2-DG) incorporation by colorimetric assay and analyzed for the radiotoxic effects of [(18)F]FDG and the expression levels of glucose transporters. Indeed, [(18)F]FDG incorporation on PET was comparable to [(18)F]FDG uptake by autoradiography and 2-DG incorporation by colorimetric assay, although radiotracer-based methods exhibited more pronounced differences between individual cell lines. As expected, these data correlated with glucose transporters 1 to 4 and hexokinase II expression in tumor cell lines and mouse fibroblasts. Notably, [(18)F]FDG incorporation resulted in low apoptotic rates, with fibroblasts being slightly more sensitive to radiotracer-induced cell death. The quantitative analysis of [(18)F]FDG uptake in living cells by PET represents a valuable and reproducible method to study tumor cell metabolism in vitro, being representative of the differences in the molecular profile of normal and tumor cell lines.
Radiolabelling diverse positron emission tomography (PET) tracers using a single digital microfluidic reactor chip.
Chen, Supin; Javed, Muhammad Rashed; Kim, Hee-Kwon; Lei, Jack; Lazari, Mark; Shah, Gaurav J; van Dam, R Michael; Keng, Pei-Yuin; Kim, Chang-Jin C J
Radiotracer synthesis is an ideal application for microfluidics because only nanogram quantities are needed for positron emission tomography (PET) imaging. Thousands of radiotracers have been developed in research settings but only a few are readily available, severely limiting the biological problems that can be studied in vivo via PET. We report the development of an electrowetting-on-dielectric (EWOD) digital microfluidic chip that can synthesize a variety of (18)F-labeled tracers targeting a range of biological processes by confirming complete syntheses of four radiotracers: a sugar, a DNA nucleoside, a protein labelling compound, and a neurotransmitter. The chip employs concentric multifunctional electrodes that are used for heating, temperature sensing, and EWOD actuation. All of the key synthesis steps for each of the four (18)F-labeled tracers are demonstrated and characterized with the chip: concentration of fluoride ion, solvent exchange, and chemical reactions. The obtained fluorination efficiencies of 90-95% are comparable to, or greater than, those achieved by conventional approaches.
Correlation between histological grade and positron emission tomography parameters in cervical carcinoma
Mocciaro, Vanessa; Scollo, Paolo; Stefano, Alessandro; Gieri, Stefania; Russo, Giorgio; Scibilia, Giuseppe; Cosentino, Sebastiano; Murè, Gabriella; Baldari, Sara; Sabini, Maria Gabriella; Fraggetta, Filippo; Gilardi, Maria Carla; Ippolito, Massimo
The aim of the present study was to evaluate the changes in cervical cancer glucose metabolism for different levels of cellular differentiation. The metabolic activity was measured by standardized uptake value (SUV), SUV normalized to lean body mass, metabolic tumor volume and total lesion glycolysis using fluorine-18 fluorodeoxyglucose positron emission tomography (PET). A correlation study of these values could be used to facilitate therapeutic choice and to improve clinical practice and outcome. This study considered 32 patients with diagnosed cervical cancers, at different International Federation of Gynecology and Obstetrics stages. Glucose metabolism was assessed by PET examination, and histological specimens were examined to determine their initial grade of differentiation. A correlation study of these values was evaluated. Histological examination showed that all cases were of squamous cell carcinoma. Regarding the differentiation of the tumor, 19 well- to moderately-differentiated tumors and 13 poorly-differentiated tumors were determined. Negative findings for correlations between metabolic parameters and initial grade of histological differentiation were found, and considering that histological grade has been shown to have no consistent prognostic value in cervical cancer treatment, PET imaging could play a significant role in cervical cancer prognosis. PMID:27446445
A behavioral and micro positron emission tomography imaging study in a rat model of hypothyroidism.
Yu, Jing; Tang, Yi-Yuang; Feng, Hong-Bo; Cheng, Xiao-Xin
Hypothyroidism leads to somatic, neuropsychological, and psychiatric changes that are similar to depression. The mechanisms underlying the behavioral abnormalities in adult onset hypothyroidism remain ambiguous. Hypothyroidism was induced in adult male Wistar rats by the maintenance of 0.05% propylthiouracil (PTU) in drinking water for 5 weeks (hypothyroid group; HP group); control rats (CON group) received an equivalent amount of water. The open field and sucrose preference tests were employed, and the link between behavioral changes and brain glucose metabolism was evaluated using micro positron emission tomography imaging. The open field test revealed slightly decreased locomotor activity and significantly reduced rearing and defecation in the hypothyroid group. Hypothyroid rats were also characterized by decreased body weight, sucrose preference, and relative sucrose intake compared to control rats. Hypothyroidism induced reduced brain glucose metabolism in the bilateral motor cortex, the caudate putamen, the cortex cingulate, the nucleus accumbens, and the frontal association cortex. A decreased sucrose preference was positively correlated with metabolic glucose changes in the caudate putamen and the nucleus accumbens. The results indicate that the activity pattern in adult onset hypothyroidism is different from the activity pattern when hypothyroidism is induced in the developmental period of the central nervous system. Decreased sucrose preference in hypothyroid rats may be attributed to anhedonia. Furthermore, these findings suggest there may be a common mechanism underlying adult onset hypothyroidism and depression.
Role of positron emission tomography-computed tomography in non-small cell lung cancer
Garg, Pankaj Kumar; Singh, Saurabh Kumar; Prakash, Gaurav; Jakhetiya, Ashish; Pandey, Durgatosh
Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell carcinoma and small cell carcinoma are the main histological subtypes and constitutes around 85% and 15% of all lung cancer respectively. Multimodality treatment plays a key role in the successful management of lung cancer depending upon the histological subtype, stage of disease, and performance status. Imaging modalities play an important role in the diagnosis and accurate staging of the disease, in assessing the response to neoadjuvant therapy, and in the follow-up of the patients. Last decade has witnessed voluminous upsurge in the use of positron emission tomography-computed tomography (PET-CT); role of PET-CT has widened exponentially in the management of lung cancer. The present article reviews the role of 18-fluoro-deoxyglucose PET-CT in the management of non small cell lung cancer with emphasis on staging of the disease and the assessment of response to neoadjuvant therapy based on available literature. PMID:27018223
Quantitative experimental monitoring of molecular diffusion in clay with positron emission tomography
NASA Astrophysics Data System (ADS)
Kulenkampff, Johannes; Zakhnini, Abdelhamid; Gründig, Marion; Lippmann-Pipke, Johanna
Clay plays a prominent role as barrier material in the geosphere. The small particle sizes cause extremely small pore sizes and induce low permeability and high sorption capacity. Transport of dissolved species by molecular diffusion, driven only by a concentration gradient, is less sensitive to the pore size. Heterogeneous structures on the centimetre scale could cause heterogeneous effects, like preferential transport zones, which are difficult to assess. Laboratory measurements with diffusion cells yield limited information on heterogeneity, and pore space imaging methods have to consider scale effects. We established positron emission tomography (PET), applying a high-resolution PET scanner as a spatially resolved quantitative method for direct laboratory observation of the molecular diffusion process of a PET tracer on the prominent scale of 1-100 mm. Although PET is rather insensitive to bulk effects, quantification required significant improvements of the image reconstruction procedure with respect to Compton scatter and attenuation. The experiments were conducted with 22Na and 124I over periods of 100 and 25 days, respectively. From the images we derived trustable anisotropic diffusion coefficients and, in addition, we identified indications of preferential transport zones. We thus demonstrated the unique potential of the PET imaging modality for geoscientific process monitoring under conditions where other methods fail, taking advantage of the extremely high detection sensitivity that is typical of radiotracer applications.
Cerebral hypometabolism in progressive supranuclear palsy studied with positron emission tomography
Foster, N.L.; Gilman, S.; Berent, S.; Morin, E.M.; Brown, M.B.; Koeppe, R.A.
Progressive supranuclear palsy (PSP) is characterized by supranuclear palsy of gaze, axial dystonia, bradykinesia, rigidity, and a progressive dementia. Pathological changes in this disorder are generally restricted to subcortical structures, yet the type and range of cognitive deficits suggest the involvement of many cerebral regions. We examined the extent of functional impairment to cerebral cortical and subcortical structures as measured by the level of glucose metabolic activity at rest. Fourteen patients with PSP were compared to 21 normal volunteers of similar age using 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography. Glucose metabolism was reduced in the caudate nucleus, putamen, thalamus, pons, and cerebral cortex, but not in the cerebellum in the patients with PSP as compared to the normal subjects. Analysis of individual brain regions revealed significant declines in cerebral glucose utilization in most regions throughout the cerebral cortex, particularly those in the superior half of the frontal lobe. Declines in the most affected regions of cerebral cortex were greater than those in any single subcortical structure. Although using conventional neuropathological techniques the cerebral cortex appears to be unaffected in PSP, significant and pervasive functional impairments in both cortical and subcortical structures are present. These observations help to account for the constellation of cognitive symptoms in individual patients with PSP and the difficulty encountered in identifying a characteristic psychometric profile for this group of patients.
Positron emission tomography in aging and dementia: effect of cerebral atrophy
Chawluk, J.B.; Alavi, A.; Dann, R.; Hurtig, H.I.; Bais, S.; Kushner, M.J.; Zimmerman, R.A.; Reivich, M.
The spatial resolution of current positron emission tomography (PET) scanners does not allow a distinction between cerebrospinal fluid (CSF) containing spaces and contiguous brain tissue. Data analysis strategies which therefore purport to quantify cerebral metabolism per unit mass brain tissue are in fact measuring a value which may be artifactually reduced due to contamination by CSF. We studied cerebral glucose metabolism (CMRglc) in 17 healthy elderly individuals and 24 patients with Alzheimer's dementia using (/sup 18/F)fluorodeoxyglucose and PET. All subjects underwent x-ray computed tomography (XCT) scanning at the time of their PET study. The XCT scans were analyzed volumetrically, in order to determine relative areas for ventricles, sulci, and brain tissue. Global CMRglc was calculated before and after correction for contamination by CSF (cerebral atrophy). A greater increase in global CMRglc after atrophy correction was seen in demented individuals compared with elderly controls (16.9% versus 9.0%, p less than 0.0005). Additional preliminary data suggest that volumetric analysis of proton-NMR images may prove superior to analysis of XCT data in quantifying the degree of atrophy. Appropriate corrections for atrophy should be employed if current PET scanners are to accurately measure actual brain tissue metabolism in various pathologic states.
Imaging Multimodalities for Dissecting Alzheimer's Disease: Advanced Technologies of Positron Emission Tomography and Fluorescence Imaging
Shimojo, Masafumi; Higuchi, Makoto; Suhara, Tetsuya; Sahara, Naruhiko
The rapid progress in advanced imaging technologies has expanded our toolbox for monitoring a variety of biological aspects in living subjects including human. In vivo radiological imaging using small chemical tracers, such as with positron emission tomography, represents an especially vital breakthrough in the efforts to improve our understanding of the complicated cascade of neurodegenerative disorders including Alzheimer's disease (AD), and it has provided the most reliable visible biomarkers for enabling clinical diagnosis. At the same time, in combination with genetically modified animal model systems, the most recent innovation of fluorescence imaging is helping establish diverse applications in basic neuroscience research, from single-molecule analysis to animal behavior manipulation, suggesting the potential utility of fluorescence technology for dissecting the detailed molecular-based consequence of AD pathophysiology. In this review, our primary focus is on a current update of PET radiotracers and fluorescence indicators beneficial for understanding the AD cascade, and discussion of the utility and pitfalls of those imaging modalities for future translational research applications. We will also highlight current cutting-edge genetic approaches and discuss how to integrate individual technologies for further potential innovations. PMID:26733795
A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular Monoamine Transporter Type 2.
Huang, Zih-Rou; Tsai, Chia-Ling; Huang, Ya-Yao; Shiue, Chyng-Yann; Tzen, Kai-Yuan; Yen, Ruoh-Fang; Hsin, Ling-Wei
In the early 1990s, 9-(+)-11C-dihydrotetrabenazine (9-(+)-11C-DTBZ) was shown to be a useful positron emission tomography (PET) imaging agent for various neurodegenerative disorders. Here, we described the radiosynthesis and evaluation of the 9-(+)-11C-DTBZ analog, 10-(+)-11C-DTBZ, as a vesicular monoamine transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-11C-DTBZ. 10-(+)-11C-DTBZ was obtained by 11C-MeI methylation with its 10 hydroxy precursor in the presence of 5 M NaOH. It had a slightly better average radiochemical yield of 35.3 ± 3.6% (decay-corrected to end of synthesis (EOS)) than did 9-(+)-11C-DTBZ (30.5 ± 2.3%). MicroPET studies showed that 10-(+)-11C-DTBZ had a striatum-to-cerebellum ratio of 3.74 ± 0.21 at 40 min post-injection, while the ratio of 9-(+)-11C-DTBZ was 2.50 ± 0.33. This indicated that 10-(+)-11C-DTBZ has a higher specific uptake in VMAT2-rich brain regions, and 10-(+)-11C-DTBZ may be a potential VMAT2 radioligand. Our experiment is the first study of 10-(+)-11C-DTBZ to include dynamic brain distribution in rat brains. PMID:27612194
A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular Monoamine Transporter Type 2
Huang, Zih-Rou; Tsai, Chia-Ling; Huang, Ya-Yao; Shiue, Chyng-Yann; Tzen, Kai-Yuan; Yen, Ruoh-Fang; Hsin, Ling-Wei
In the early 1990s, 9-(+)-11C-dihydrotetrabenazine (9-(+)-11C-DTBZ) was shown to be a useful positron emission tomography (PET) imaging agent for various neurodegenerative disorders. Here, we described the radiosynthesis and evaluation of the 9-(+)-11C-DTBZ analog, 10-(+)-11C-DTBZ, as a vesicular monoamine transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-11C-DTBZ. 10-(+)-11C-DTBZ was obtained by 11C-MeI methylation with its 10 hydroxy precursor in the presence of 5 M NaOH. It had a slightly better average radiochemical yield of 35.3 ± 3.6% (decay-corrected to end of synthesis (EOS)) than did 9-(+)-11C-DTBZ (30.5 ± 2.3%). MicroPET studies showed that 10-(+)-11C-DTBZ had a striatum-to-cerebellum ratio of 3.74 ± 0.21 at 40 min post-injection, while the ratio of 9-(+)-11C-DTBZ was 2.50 ± 0.33. This indicated that 10-(+)-11C-DTBZ has a higher specific uptake in VMAT2-rich brain regions, and 10-(+)-11C-DTBZ may be a potential VMAT2 radioligand. Our experiment is the first study of 10-(+)-11C-DTBZ to include dynamic brain distribution in rat brains. PMID:27612194
Dynamic study of methionine positron emission tomography in patients with glioblastoma with oligodendroglial components.
Yano, Hirohito; Ohe, Naoyuki; Nakayama, Noriyuki; Nomura, Yu-Ichi; Miwa, Kazuhiro; Shinoda, Jun; Iwama, Toru
Anaplastic oligoastrocytoma (AOA) with necrosis is classified as glioblastoma (GBM) with oligodendroglioma component (GBMO), according to the 2007 World Health Organization classification. The prognosis of GBMO remains controversial because definitive diagnostic criteria regarding the percentage of the oligodendroglial components (OC) in the GBM do not exist. We previously reported dynamic methionine (MET) positron emission tomography (PET) in patients with these tumors. A significant decrease in the MET signal was seen in oligodendrocytic tumors, in contrast to a significant MET increase in GBMs. In this study, we analyzed the dynamic MET PET signal in four patients with primary (n = 2) and secondary (n = 2) GBMOs. Static PET scanning was performed in three consecutive phases. Both cases of primary GBMOs and one case of secondary GBMO presented with a gradual decrease in MET PET signal over the consecutive phases. In contrast, the remaining case of secondary GBMO presented with a pattern of slight increase. It is likely that the dynamic change of MET in patients with GBMO resemble those in patients with oligodendroglial tumor, however, further studies are needed to confirm them. We discuss the mechanisms from a viewpoint of pathological findings.
(18)F-Labeling of Mannan for Inflammation Research with Positron Emission Tomography.
Li, Xiang-Guo; Hagert, Cecilia; Siitonen, Riikka; Virtanen, Helena; Sareila, Outi; Liljenbäck, Heidi; Tuisku, Jouni; Knuuti, Juhani; Bergman, Jörgen; Holmdahl, Rikard; Roivainen, Anne
Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice, and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 ((18)F) and study the (18)F-labeled mannan in vitro and in vivo with positron emission tomography (PET). Accordingly, mannan has been transformed into (18)F-fluoromannan with (18)F-bicyclo[6.1.0]nonyne. In mouse aorta, the binding of [(18)F]fluoromannan to the atherosclerotic lesions was clearly visualized and was significantly higher compared to blocking assays (P < 0.001) or healthy mouse aorta (P < 0.001). In healthy rats the [(18)F]fluoromannan radioactivity accumulated largely in the macrophage-rich organs such as liver, spleen, and bone marrow and the excess excreted in urine. Furthermore, the corresponding (19)F-labeled mannan has been used to induce psoriasis and psoriatic arthritis in mice, which indicates that the biological function of mannan is preserved after the chemical modifications.
New techniques for positron emission tomography in the study of human neurological disorders
Kuhl, D.E.
This progress report represents a summary of our performance during the two year period following initial start-up of these research activities at Michigan. Productivity has been excellent; already over 47 papers and abstracts have been published or accepted for publication from this still young program. They represent significant contributions to extending the technology of positron emission tomography in the study of human neurological disorders. Our focus is to develop more cost effective and efficient means for producing new functionally specific tracers and simpler, less expensive, means for acquiring and interpreting quantitative data. These improved processes are required for the future growth of PET as a sophisticated research tool and for the transfer of this technology to clinical use. Our approach concentrates on two separate yet related areas, radiosynthesis and data analysis. In subproject 1, Drs. Jewett and Mulholland have introduced innovative methods for improving 11C and 18F synthetic processes. In Subproject 2, Dr. Hutchins has laid the foundations for an objective analysis of the limitations and opportunities for quantifying regional PET data. In Subproject 3, Dr. Koeppe has extended rapid techniques for parameter estimation in kinetic modeling of new ligands. Finally, in Subproject 4, Dr. Frey has applied kinetic analysis to ligand tracing of the cholinergic neurotransmitter system in animal and human brain. These DOE supported studies have direct impact on clinical research here and elsewhere which is expected to improve diagnosis and treatment of degenerative neurological diseases, mental illness and brain tumors. 47 refs., 7 figs., 4 tabs.
Kinetic analysis of [11C]vorozole binding in the human brain with positron emission tomography.
Logan, Jean; Kim, Sung Won; Pareto, Deborah; Telang, Frank; Wang, Gene-Jack; Fowler, Joanna S; Biegon, Anat
Using positron emission tomography, we investigated the kinetics of [11C]vorozole ([11C]VOR), a radiotracer for the enzyme aromatase that catalyzes the last step in estrogen biosynthesis. Six subjects were scanned under baseline conditions followed by retest 2 weeks later. The retest was followed by a blocking study with 2.5 mg of the aromatase inhibitor letrozole. The binding potential (BP(A)ND) was estimated from a Lassen plot using the total tissue distribution volume (VT) for baseline and blocked. for the thalamus was found to be 15 times higher than that for the cerebellum. From the letrozole studies, we found that [11C]VOR exhibits a slow binding compartment (small k4) that has a nonspecific and a blockable component. Because of the sensitivity of VT to variations in k4, a common value was used for the four highest binding regions. We also considered the tissue uptake to plasma ratio for 60 to 90 minutes as an outcome measure. Using the ratio method, the difference between the highest and lowest was 2.4 compared to 3.5 for the VT. The ratio method underestimates the high regions but is less variable and may be more suitable for patient studies. Because of its kinetics and distribution, this tracer is not a candidate for a bolus infusion or reference tissue methods.
Evaluation and optimization of occupational eye lens dosimetry during positron emission tomography (PET) procedures.
Guiu-Souto, Jacobo; Sánchez-García, Manuel; Vázquez-Vázquez, Rubén; Otero, Carlos; Luna, Victor; Mosquera, Javier; Busto, Ramón Lobato; Aguiar, Pablo; Ruibal, Álvaro; Pardo-Montero, Juan; Pombar-Cameán, Miguel
The last recommendations of the International Commission on Radiological Protection for eye lens dose suggest an important reduction on the radiation limits associated with early and late tissue reactions. The aim of this work is to quantify and optimize the eye lens dose associated to nurse staff during positron emission tomography (PET) procedures. PET is one of the most important diagnostic methods of oncological and neurological cancer disease involving an important number of workers exposed to the high energy isotope F-18. We characterize the relevant stages as preparation and administration of monodose syringes in terms of occupational dose. A direct reading silicon dosimeter was used to measure the lens dose to staff. The highest dose of radiation was observed during preparation of the fluorodesoxyglucose (FDG) syringes. By optimizing a suitable vials' distribution of FDG we find an important reduction in occupational doses. Extrapolation of our data to other clinical scenarios indicates that, depending on the work load and/or syringes activity, safety limits of the dose might be exceeded.
The Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in Thyroid Neoplasms
Law, Tsz Ting
18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has established itself as an important imaging modality in many oncological and nononcological specialties and, as a consequence, it is increasingly being used in clinical practice. Since the first report of FDG being taken up by metastatic differentiated thyroid carcinoma (DTC) cells >20 years ago, various groups of investigators have explored the potential role of FDG-PET scanning in patients with benign and malignant thyroid neoplasms. With the increasing demand for FDG-PET scanning, clinicians are faced with the challenge of managing an increasing number of FDG-PET–detected thyroid incidentalomas because their significance remains unclear. The aims of this review are to address some of these issues, specifically, the clinical significance of FDG-PET–detected thyroid incidentalomas, the ability of FDG-PET to characterize thyroid nodules, especially those with indeterminate fine needle aspiration cytology results, and the role of FDG-PET in patients with confirmed primary DTC and with suspected recurrent DTC, by reviewing the current literature. PMID:21378078
F-18 Fluorodeoxyglucose Positron Emission Tomography study of Impaired Emotion Processing in First Episode Schizophrenia
Choudhary, Mona; Kumar, Arvind; Tripathi, Madhavi; Bhatia, Triptish; Shivakumar, Venkataram; Beniwal, Ram Pratap; Gur, Ruben C.; Gur, Raquel E.; Nimgaonkar, Vishwajit L.
Background Schizophrenia cases have consistently shown to have behavioural and neurofunctional abnormalities but studies during early course are scarce. The present work assesses the performance of acute first episode schizophrenia cases on correlation of a facial emotion perception task with brain function using Fluorine-18 Fluorodeoxyglucose (FDG) positron emission tomography (PET). Methods Twenty First episode schizophrenia cases and 20 matched healthy controls living in the community were enrolled. For cases, longest duration of illness was one year and treatment with neuroleptic did not exceed two weeks on the day of scan. To measure facial emotion perception (FEP) both groups were administered the Emotion battery from the Penn Computerized Battery followed by PET acquisition. SPM 8 analysis for group differences at p<0.001 was performed. Results Schizophrenia subjects showed hypoactivation of bilateral prefrontal cortices and fusiform gyrii, with significant hyperactivation of bilateral basal ganglia and left precuneus. Positive correlation of metabolism in prefrontal cortex and performance indices on emotions domain was seen. No correlation of CPZ equivalent days with metabolism in basal ganglia was observed. Conclusions The performance of schizophrenia cases on FEP task was significantly impaired in comparison to the control group. Brain regions implicated in emotion processing showed hypometabolism in cases as compared to controls. Failure of schizophrenia cases to optimally recruit brain circuitry may be contributing to deficits on FEP task. These findings suggest inherent deficits in neural circuitry of emotion processing in schizophrenia; devoid of confounding effects of neuroleptics and duration of illness. PMID:25655909
Positron Emission Tomography Imaging of Tumor Cell Metabolism and Application to Therapy Response Monitoring
Challapalli, Amarnath; Aboagye, Eric O.
Cancer cells do reprogram their energy metabolism to enable several functions, such as generation of biomass including membrane biosynthesis, and overcoming bioenergetic and redox stress. In this article, we review both established and evolving radioprobes developed in association with positron emission tomography (PET) to detect tumor cell metabolism and effect of treatment. Measurement of enhanced tumor cell glycolysis using 2-deoxy-2-[18F]fluoro-D-glucose is well established in the clinic. Analogs of choline, including [11C]choline and various fluorinated derivatives are being tested in several cancer types clinically with PET. In addition to these, there is an evolving array of metabolic tracers for measuring intracellular transport of glutamine and other amino acids or for measuring glycogenesis, as well as probes used as surrogates for fatty acid synthesis or precursors for fatty acid oxidation. In addition to providing us with opportunities for examining the complex regulation of reprogramed energy metabolism in living subjects, the PET methods open up opportunities for monitoring pharmacological activity of new therapies that directly or indirectly inhibit tumor cell metabolism. PMID:26973812
Glucose utilization in a patient with hepatoma and hypoglycemia. Assessment by a positron emission tomography.
Eastman, R C; Carson, R E; Orloff, D G; Cochran, C S; Perdue, J F; Rechler, M M; Lanau, F; Roberts, C T; Shapiro, J; Roth, J
Tumor glucose use in patients with non-islet-cell tumors has been difficult to measure, particularly in hepatoma, because of hepatic involvement by neoplasm. We studied a patient with nonhepatic recurrence of hepatoma after successful liver transplantation. Tumor tissue contained messenger RNA for insulin-like growth factor-II (IGF-II), and circulating high molecular weight components and E-peptide of IGF-II were increased. Glucose use measured by isotope dilution with [3-3H]glucose was 7.94 mg/kg fat-free mass per min, and splanchnic glucose production was 0.93 mg/kg fat-free mass per min. Glucose uptake and glucose model parameters were independently measured in tissues by positron emission tomography with 18F-fluoro-2-deoxy-D-glucose. Glucose uptake by heart muscle, liver, skeletal muscle, and neoplasm accounted for 0.8, 14, 44, and 15% of total glucose use, respectively. Model parameters in liver and neoplasm were not significantly different, and glucose transport and phosphorylation were twofold and fourfold greater than in muscle. This suggests that circulating IGF-II-like proteins are partial insulin agonists, and that hypoglycemia in hepatoma with IGF-II production is predominantly due to glucose uptake by skeletal muscle and suppression of glucose production. PMID:1318326
New Glucocyclic RGD Dimers for Positron Emission Tomography Imaging of Tumor Integrin Receptors.
Lee, Ji Woong; Park, Ji-Ae; Lee, Yong Jin; Shin, Un Chol; Kim, Suhng Wook; Kim, Byung Il; Lim, Sang Moo; An, Gwang Il; Kim, Jung Young; Lee, Kyo Chul
Most studies of radiolabeled arginine-glycine-aspartic acid (RGD) peptides have shown in vitro affinity for integrin ανβ3, allowing for the targeting of receptor-positive tumors in vivo. However, major differences have been found in the pharmacokinetic profiles of different radiolabeled RGD peptide analogs. The purposes of this study were to prepare (64)Cu-DOTA-gluco-E[c(RGDfK)]2 (R8), (64)Cu-NOTA-gluco-E[c(RGDfK)]2 (R9), and (64)Cu-NODAGA-gluco-E[c(RGDfK)]2 (R10) and compare their pharmacokinetics and tumor imaging properties using small-animal positron emission tomography (PET). All three compounds were produced with high specific activity within 10 minutes. The IC50 values were similar for all the substances, and their affinities were greater than that of c(RGDyK). R8, R9, and R10 were stable for 24 hours in human and mouse serums and showed high uptake in U87MG tumors with high tumor-to-blood ratios. Compared to the control, a cyclic RGD peptide dimer without glucosamine, R10, showed low uptake in the liver. Because of their good imaging qualities and improved pharmacokinetics, (64)Cu-labeled dimer RGD conjugates (R8, R9, and R10) may have potential applications as PET radiotracers. R9 (NOTA) with highly in vivo stability consequentially showed an improved PET tumor uptake than R8 (DOTA) or R10 (NODAGA). PMID:27403677
TOPICAL REVIEW: Biological imaging in radiation therapy: role of positron emission tomography
NASA Astrophysics Data System (ADS)
Nestle, Ursula; Weber, Wolfgang; Hentschel, Michael; Grosu, Anca-Ligia
In radiation therapy (RT), staging, treatment planning, monitoring and evaluation of response are traditionally based on computed tomography (CT) and magnetic resonance imaging (MRI). These radiological investigations have the significant advantage to show the anatomy with a high resolution, being also called anatomical imaging. In recent years, so called biological imaging methods which visualize metabolic pathways have been developed. These methods offer complementary imaging of various aspects of tumour biology. To date, the most prominent biological imaging system in use is positron emission tomography (PET), whose diagnostic properties have clinically been evaluated for years. The aim of this review is to discuss the valences and implications of PET in RT. We will focus our evaluation on the following topics: the role of biological imaging for tumour tissue detection/delineation of the gross tumour volume (GTV) and for the visualization of heterogeneous tumour biology. We will discuss the role of fluorodeoxyglucose-PET in lung and head and neck cancer and the impact of amino acids (AA)-PET in target volume delineation of brain gliomas. Furthermore, we summarize the data of the literature about tumour hypoxia and proliferation visualized by PET. We conclude that, regarding treatment planning in radiotherapy, PET offers advantages in terms of tumour delineation and the description of biological processes. However, to define the real impact of biological imaging on clinical outcome after radiotherapy, further experimental, clinical and cost/benefit analyses are required.
Iterative reconstruction using a Monte Carlo based system transfer matrix for dedicated breast positron emission tomography.
Saha, Krishnendu; Straus, Kenneth J; Chen, Yu; Glick, Stephen J
To maximize sensitivity, it is desirable that ring Positron Emission Tomography (PET) systems dedicated for imaging the breast have a small bore. Unfortunately, due to parallax error this causes substantial degradation in spatial resolution for objects near the periphery of the breast. In this work, a framework for computing and incorporating an accurate system matrix into iterative reconstruction is presented in an effort to reduce spatial resolution degradation towards the periphery of the breast. The GATE Monte Carlo Simulation software was utilized to accurately model the system matrix for a breast PET system. A strategy for increasing the count statistics in the system matrix computation and for reducing the system element storage space was used by calculating only a subset of matrix elements and then estimating the rest of the elements by using the geometric symmetry of the cylindrical scanner. To implement this strategy, polar voxel basis functions were used to represent the object, resulting in a block-circulant system matrix. Simulation studies using a breast PET scanner model with ring geometry demonstrated improved contrast at 45% reduced noise level and 1.5 to 3 times resolution performance improvement when compared to MLEM reconstruction using a simple line-integral model. The GATE based system matrix reconstruction technique promises to improve resolution and noise performance and reduce image distortion at FOV periphery compared to line-integral based system matrix reconstruction.
Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.
Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang
Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259
Test-Retest Repeatability of Myocardial Blood Flow Measurements using Rubidium-82 Positron Emission Tomography
NASA Astrophysics Data System (ADS)
Efseaff, Matthew
Rubidium-82 positron emission tomography (PET) imaging has been proposed for routine myocardial blood flow (MBF) quantification. Few studies have investigated the test-retest repeatability of this method. Same-day repeatability of rest MBF imaging was optimized with a highly automated analysis program using image-derived input functions and a dual spillover correction (SOC). The effects of heterogeneous tracer infusion profiles and subject hemodynamics on test-retest repeatability were investigated at rest and during hyperemic stress. Factors affecting rest MBF repeatability included gender, suspected coronary artery disease, and dual SOC (p < 0.001). The best repeatability coefficient for same-day rest MBF was 0.20 mL/min/g using a six-minute scan-time, iterative reconstruction, dual SOC, resting rate-pressure-product (RPP) adjustment, and a left atrium image-derived input function. The serial study repeatabilities of the optimized protocol in subjects with homogeneous RPPs and tracer infusion profiles was 0.19 and 0.53 mL/min/g at rest and stress, and 0.95 for stress / rest myocardial flow reserve (MFR). Subjects with heterogeneous tracer infusion profiles and hemodynamic conditions had significantly less repeatable MBF measurements at rest, stress, and stress/rest flow reserve (p < 0.05).
The role of positron emission tomography in the evaluation of myocardial ischemia in women.
Taqueti, Viviany R; Dorbala, Sharmila
Cardiovascular disease continues to be the number one cause of death in women, yet most women are unaware of their risk. Over the last decade, radionuclide myocardial perfusion imaging with positron emission tomography (PET) has become a powerful tool for the diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). This editorial viewpoint will review the maturing role of PET imaging in women, particularly as applied to the evaluation of ischemic heart disease. Specifically, we focus on distinct advantages offered by PET imaging in the evaluation of myocardial ischemia in women: (1) improved diagnostic accuracy, including in the presence of breast or adipose tissue and small left ventricular cavity size, (2) decreased radiation exposure through the use of short-lived radiopharmaceuticals, and (3) the ability to quantify myocardial blood flow and coronary flow reserve to diagnose ischemia, even in the absence of obstructive CAD. As such, cardiac PET perfusion imaging stands to play a unique role in defining the diagnosis and prognosis of women with ischemic heart disease, while also guiding new treatment strategies for their more prevalent cardiovascular disease phenotypes. PMID:27488383
Biological Response of Positron Emission Tomography Scan Exposure and Adaptive Response in Humans
Schnarr, Kara; Carter, Timothy F.; Gillis, Daniel; Webber, Colin; Dayes, Ian; Dolling, Joanna A.; Gulenchyn, Karen; Boreham, Douglas R.
The biological effects of exposure to radioactive fluorodeoxyglucose (18F-FDG) were investigated in the lymphocytes of patients undergoing positron emission tomography (PET) procedures. Low-dose, radiation-induced cellular responses were measured using 3 different end points: (1) apoptosis; (2) chromosome aberrations; and (3) γH2AX foci formation. The results showed no significant change in lymphocyte apoptosis, or chromosome aberrations, as a result of in vivo 18F-FDG exposure, and there was no evidence the PET scan modified the apoptotic response of lymphocytes to a subsequent 2 Gy in vitro challenge irradiation. However, lymphocytes sampled from patients following a PET scan showed an average of 22.86% fewer chromosome breaks and 39.16% fewer dicentrics after a subsequent 2 Gy in vitro challenge irradiation. The effect of 18F-FDG exposure on phosphorylation of histone H2AX (γH2AX) in lymphocytes of patients showed a varied response between individuals. The relationship between γH2AX foci formation and increasing activity of 18F-FDG was not directly proportional to dose. This variation is most likely attributed to differences in the factors that combine to constitute an individual's radiation response. In summary, the results of this study indicate18F-FDG PET scans may not be detrimental but can elicit variable responses between individuals and can modify cellular response to subsequent radiation exposures. PMID:26740810
EEG, transmission computed tomography, and positron emission tomography with fluorodeoxyglucose /sup 18/F. Their use in adults with gliomas
Newmark, M.E.; Theodore, W.H.; Sato, S.; De La Paz, R.; Patronas, N.; Brooks, R.; Jabbari, B.; Di Chiro, G.
We evaluated the relationship between findings from EEG, transmission computed tomography (CT), and positron emission tomography in 23 adults with gliomas. The cortical metabolic rate was suppressed in patients with and without focal slowing. Focal delta activity was not related to involvement of gray or white matter. Rhythmic delta activity and focal attenuation of background amplitude on EEG, however, were correlated with involvement of the thalamus.
Retroperitoneal Endometriosis: A Possible Cause of False Positive Finding at 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Maffione, Anna Margherita; Panzavolta, Riccardo; Lisato, Laura Camilla; Ballotta, Maria; D'Isanto, Mariangela Zanforlini; Rubello, Domenico
Endometriosis is a frequent and clinically relevant problem in young women. Laparoscopy is still the gold standard for the diagnosis of endometriosis, but frequently both morphologic and functional imaging techniques are involved in the diagnostic course before achieving a conclusive diagnosis. We present a case of a patient affected by infiltrating retroperitoneal endometriosis falsely interpreted as a malignant mass by contrast-enhanced magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography/computed tomography. PMID:26097425
Noninvasive quantification of regional blood flow in the human heart using N-13 ammonia and dynamic positron emission tomographic imaging
Hutchins, G.D.; Schwaiger, M.; Rosenspire, K.C.; Krivokapich, J.; Schelbert, H.; Kuhl, D.E. )
Evaluation of regional myocardial blood flow by conventional scintigraphic techniques is limited to the qualitative assessment of regional tracer distribution. Dynamic imaging with positron emission tomography allows the quantitative delineation of myocardial tracer kinetics and, hence, the measurement of physiologic processes such as myocardial blood flow. To test this hypothesis, positron emission tomographic imaging in combination with N-13 ammonia was performed at rest and after pharmacologically induced vasodilation in seven healthy volunteers. Myocardial and blood time-activity curves derived from regions of interest over the heart and ventricular chamber were fitted using a three compartment model for N-13 ammonia, yielding rate constants for tracer uptake and retention. Myocardial blood flow (K1) averaged 88 +/- 17 ml/min per 100 g at rest and increased to 417 +/- 112 ml/min per 100 g after dipyridamole infusion (0.56 mg/kg) and handgrip exercise. The coronary reserve averaged 4.8 +/- 1.3 and was not significantly different in the septal, anterior and lateral walls of the left ventricle. Blood flow values showed only a minor dependence on the correction for blood metabolites of N-13 ammonia. These data demonstrate that quantification of regional myocardial blood flow is feasible by dynamic positron emission tomographic imaging. The observed coronary flow reserve after dipyridamole is in close agreement with the results obtained by invasive techniques, indicating accurate flow estimates over a wide range. Thus, positron emission tomography may provide accurate and noninvasive definition of the functional significance of coronary artery disease and may allow the improved selection of patients for revascularization.
Mediastinal lymph node staging of non-small-cell lung cancer: a prospective comparison of computed tomography and positron emission tomography.
Scott, W J; Gobar, L S; Terry, J D; Dewan, N A; Sunderland, J J
We compared the abilities of positron emission tomography and computed tomography to detect N2 or N3 lymph node metastases (N2 or N3) in patients with lung cancer. Positron emission tomography detects increased rates of glucose uptake, characteristic of malignant cells. Patients with peripheral tumors smaller than 2 cm and a normal mediastinum were ineligible. All patients underwent computed tomography, positron emission tomography, and surgical staging. The American Thoracic Society lymph node map was used. Computed and positron emission tomographic scans were read by separate radiologists blinded to surgical staging results. Lymph nodes were "positive" by computed tomography if larger than 1.0 cm in short-axis diameter. Standardized uptake values were recorded from areas on positron emission tomography corresponding to those from which biopsy specimens were taken; if greater than 4.2, they were called "positive." Seventy-five lymph node stations (2.8 per patient) were analyzed in 27 patients. Computed tomography incorrectly staged the mediastinum as positive for metastases in three patients and as negative for metastases in three patients. Sensitivity and specificity of computed tomographic scans were 67% and 83%, respectively. Positron emission tomography correctly staged the mediastinum in all 27 patients. When analyzed by individual node station, there were four false positive and four false negative results by computed tomography (sensitivity = 60%, specificity = 93%, positive predictive value = 60%). Positron emission tomography mislabeled one node station as positive (100% sensitive, 98% specific, positive predictive value 91%). The differences were significant when the data were analyzed both for individual lymph node stations (p = 0.039) and for patients (p = 0.031) (McNemar test). Positron emission tomography and computed tomography are more accurate than computed tomography alone in detecting mediastinal lymph node metastases from non-small-cell lung
Molecular imaging of cancer with copper-64 radiopharmaceuticals and positron emission tomography (PET).
Shokeen, Monica; Anderson, Carolyn J
Molecular imaging has evolved over the past several years into an important tool for diagnosing, understanding, and monitoring disease. Molecular imaging has distinguished itself as an interdisciplinary field, with contributions from chemistry, biology, physics, and medicine. The cross-disciplinary impetus has led to significant achievements, such as the development of more sensitive imaging instruments and robust, safer radiopharmaceuticals, thereby providing more choices to fit personalized medical needs. Molecular imaging is making steadfast progress in the field of cancer research among others. Cancer is a challenging disease, characterized by heterogeneity, uncontrolled cell division, and the ability of cancer cells to invade other tissues. Researchers are addressing these challenges by aggressively identifying and studying key cancer-specific biomarkers such as growth factor receptors, protein kinases, cell adhesion molecules, and proteases, as well as cancer-related biological processes such as hypoxia, apoptosis, and angiogenesis. Positron emission tomography (PET) is widely used by clinicians in the United States as a diagnostic molecular imaging tool. Small-animal PET systems that can image rodents and generate reconstructed images in a noninvasive manner (with a resolution as low as 1 mm) have been developed and are used frequently, facilitating radiopharmaceutical development and drug discovery. Currently, [(18)F]-labeled 2-fluorodeoxyglucose (FDG) is the only PET radiotracer used for routine clinical evaluation (primarily for oncological imaging). There is now increasing interest in nontraditional positron-emitting radionuclides, particularly those of the transition metals, for imaging with PET because of increased production and availability. Copper-based radionuclides are currently being extensively evaluated because they offer a varying range of half-lives and positron energies. For example, the half-life (12.7 h) and decay properties (beta(+), 0
Diagnosis of Alzheimer-type dementia: a preliminary comparison of positron emission tomography and proton magnetic resonance
Friedland, R.P.; Budinger, T.F.; Brant-Zawadzki, M.; Jagust, W.J.
The use of positron emission tomography with (18F)-2-fluoro-2-deoxy-D-glucose (FDG) to study glucose metabolism in dementia is described and compared with the use of magnetic resonance imaging. These studies suggest that physiological imaging with PET may be superior to MR as it is currently used in the diagnosis of dementia-like diseases. Pet is currently limited to a few centers; however, single photon emission CT can provide regional physiological data without the need for a local cyclotron. 15 references, 2 tables.
Positron Emission Tomography (PET) Evaluation After Initial Chemotherapy and Radiation Therapy Predicts Local Control in Rhabdomyosarcoma
Dharmarajan, Kavita V.; Wexler, Leonard H.; Gavane, Somali; Fox, Josef J.; Schoder, Heiko; Tom, Ashlyn K.; Price, Alison N.; Meyers, Paul A.; Wolden, Suzanne L.
Purpose: 18-fluorodeoxyglucose positron emission tomography (PET) is already an integral part of staging in rhabdomyosarcoma. We investigated whether primary-site treatment response characterized by serial PET imaging at specific time points can be correlated with local control. Patients and Methods: We retrospectively examined 94 patients with rhabdomyosarcoma who received initial chemotherapy 15 weeks (median) before radiotherapy and underwent baseline, preradiation, and postradiation PET. Baseline PET standardized uptake values (SUVmax) and the presence or absence of abnormal uptake (termed PET-positive or PET-negative) both before and after radiation were examined for the primary site. Local relapse-free survival (LRFS) was calculated according to baseline SUVmax, PET-positive status, and PET-negative status by the Kaplan-Meier method, and comparisons were tested with the log-rank test. Results: The median patient age was 11 years. With 3-year median follow-up, LRFS was improved among postradiation PET-negative vs PET-positive patients: 94% vs 75%, P=.02. By contrast, on baseline PET, LRFS was not significantly different for primary-site SUVmax {<=}7 vs >7 (median), although the findings suggested a trend toward improved LRFS: 96% for SUVmax {<=}7 vs 79% for SUVmax >7, P=.08. Preradiation PET also suggested a statistically insignificant trend toward improved LRFS for PET-negative (97%) vs PET-positive (81%) patients (P=.06). Conclusion: Negative postradiation PET predicted improved LRFS. Notably, 77% of patients with persistent postradiation uptake did not experience local failure, suggesting that these patients could be closely followed up rather than immediately referred for intervention. Negative baseline and preradiation PET findings suggested statistically insignificant trends toward improved LRFS. Additional study may further understanding of relationships between PET findings at these time points and outcome in rhabdomyosarcoma.
Motion management in positron emission tomography/computed tomography for radiation treatment planning.
Bettinardi, Valentino; Picchio, Maria; Di Muzio, Nadia; Gilardi, Maria Carla
Hybrid positron emission tomography (PET)/computed tomography (CT) scanners combine, in a unique gantry, 2 of the most important diagnostic imaging systems, a CT and a PET tomograph, enabling anatomical (CT) and functional (PET) studies to be performed in a single study session. Furthermore, as the 2 scanners use the same spatial coordinate system, the reconstructed CT and PET images are spatially co-registered, allowing an accurate localization of the functional signal over the corresponding anatomical structure. This peculiarity of the hybrid PET/CT system results in improved tumor characterization for oncological applications, and more recently, it was found to be also useful for target volume definition (TVD) and treatment planning in radiotherapy (RT) applications. In fact, the use of combined PET/CT information has been shown to improve the RT treatment plan when compared with that obtained by a CT alone. A limiting factor to the accuracy of TVD by PET/CT is organ and tumor motion, which is mainly due to patient respiration. In fact, respiratory motion has a degrading effect on PET/CT image quality, and this is also critical for TVD, as it can lead to possible tumor missing or undertreatment. Thus, the management of respiratory motion is becoming an increasingly essential component in RT treatment planning; indeed, it has been recognized that the use of personalized motion information can improve TVD and, consequently, permit increased tumor dosage while sparing surrounding healthy tissues and organs at risk. This review describes the methods used for motion management in PET/CT for radiation treatment planning. The article covers the following: (1) problems caused by organ and lesion motion owing to respiration, and the artifacts generated on CT, PET, and PET/CT images; (2) data acquisition and processing techniques used to manage respiratory motion in PET/CT studies; and (3) the use of personalized motion information for TVD and radiation treatment planning.
Positron Emission Tomography Image-Guided Drug Delivery: Current Status and Future Perspectives
Positron emission tomography (PET) is an important modality in the field of molecular imaging, which is gradually impacting patient care by providing safe, fast, and reliable techniques that help to alter the course of patient care by revealing invasive, de facto procedures to be unnecessary or rendering them obsolete. Also, PET provides a key connection between the molecular mechanisms involved in the pathophysiology of disease and the according targeted therapies. Recently, PET imaging is also gaining ground in the field of drug delivery. Current drug delivery research is focused on developing novel drug delivery systems with emphasis on precise targeting, accurate dose delivery, and minimal toxicity in order to achieve maximum therapeutic efficacy. At the intersection between PET imaging and controlled drug delivery, interest has grown in combining both these paradigms into clinically effective formulations. PET image-guided drug delivery has great potential to revolutionize patient care by in vivo assessment of drug biodistribution and accumulation at the target site and real-time monitoring of the therapeutic outcome. The expected end point of this approach is to provide fundamental support for the optimization of innovative diagnostic and therapeutic strategies that could contribute to emerging concepts in the field of "personalized medicine". This review focuses on the recent developments in PET image-guided drug delivery and discusses intriguing opportunities for future development. The preclinical data reported to date are quite promising, and it is evident that such strategies in cancer management hold promise for clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in enhanced quality of life for cancer patients. PMID:24865108
Theory of Mind and Schizophrenia: A Positron Emission Tomography Study of Medication-Free Patients
Andreasen, Nancy C.; Calage, Chadi A.; O'Leary, Daniel S.
Background: "Theory of mind" (TOM) refers to the ability to attribute mental states (ie, beliefs and goals) to one's self and others and to recognize that behaviors are guided by these mental states. This capacity, critical for social competence, is impaired in schizophrenia. We undertook a study of TOM in a group of patients with schizophrenia and healthy controls. Method: We used positron emission tomography to identify the neural circuits recruited during a verbal task that required participants to attribute mental states to a character in a story of their creation. The comparison task consisted of reading aloud a neutral story, controlling for the speech component of the task. Results: Patients and controls generated the same percentage of TOM utterances. However, the two groups had markedly different patterns of brain activation. Compared with controls, patients had a lower blood flow in multiple regions in the left hemisphere including the frontal and visual association cortices, posterior hippocampus, and insula. The flow was also lower in contralateral areas in the lateral cerebellum and vermis, thalamus, and posterior insula. On the other hand, the flow was higher in the patients predominantly in the right hemisphere, including multiple frontal and parietal regions, insula, visual association cortex, and pulvinar. Discussion: The areas of lower flow are consistent with previous studies indicating impairment in recruiting cortical-cerebellar circuitry in schizophrenia. The areas of higher flow may reflect a need to draw on the right hemisphere to compensate for deficits in left hemisphere networks that include frontal cortex, anterior cingulate, cerebellum, and thalamus. PMID:18559406
Dosage optimization in positron emission tomography: state-of-the-art methods and future prospects
Karakatsanis, Nicolas A; Fokou, Eleni; Tsoumpas, Charalampos
Positron emission tomography (PET) is widely used nowadays for tumor staging and therapy response in the clinic. However, average PET radiation exposure has increased due to higher PET utilization. This study aims to review state-of-the-art PET tracer dosage optimization methods after accounting for the effects of human body attenuation and scan protocol parameters on the counting rate. In particular, the relationship between the noise equivalent count rate (NECR) and the dosage (NECR-dosage curve) for a range of clinical PET systems and body attenuation sizes will be systematically studied to prospectively estimate the minimum dosage required for sufficiently high NECR. The optimization criterion can be determined either as a function of the peak of the NECR-dosage curve or as a fixed NECR score when NECR uniformity across a patient population is important. In addition, the systematic NECR assessments within a controllable environment of realistic simulations and phantom experiments can lead to a NECR-dosage response model, capable of predicting the optimal dosage for every individual PET scan. Unlike conventional guidelines suggesting considerably large dosage levels for obese patients, NECR-based optimization recommends: i) moderate dosage to achieve 90% of peak NECR for obese patients, ii) considerable dosage reduction for slimmer patients such that uniform NECR is attained across the patient population, and iii) prolongation of scans for PET/MR protocols, where longer PET acquisitions are affordable due to lengthy MR sequences, with motion compensation becoming important then. Finally, the need for continuous adaptation of dosage optimization to emerging technologies will be discussed. PMID:26550543
Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography
Weinstein, Edward A.; Ordonez, Alvaro A.; DeMarco, Vincent P.; Murawski, Allison M.; Pokkali, Supriya; MacDonald, Elizabeth M.; Klunk, Mariah; Mease, Ronnie C.; Pomper, Martin G.; Jain, Sanjay K.
The Enterobacteriaceae are a family of rod-shaped Gram-negative bacteria that normally inhabit the gastrointestinal tract and are the most common cause of Gram-negative bacterial infections in humans. In addition to causing serious multidrug-resistant, hospital-acquired infections, a number of Enterobacteriaceae species are also recognized as biothreat pathogens. As a consequence, new tools are urgently needed to specifically identify and localize infections due to Enterobacteriaceae and to monitor antimicrobial efficacy. In this report, we used commercially available 2-[18F]-fluorodeoxyglucose (18F-FDG) to produce 2-[18F]-fluorodeoxysorbitol (18F-FDS), a radioactive probe for Enterobacteriaceae, in 30 min. 18F-FDS selectively accumulated in Enterobacteriaceae, but not in Gram-positive bacteria or healthy mammalian or cancer cells in vitro. In a murine myositis model, 18F-FDS positron emission tomography (PET) rapidly differentiated true infection from sterile inflammation with a limit of detection of 6.2 ± 0.2 log10 colony-forming units (CFU) for Escherichia coli. Our findings were extended to models of mixed Gram-positive and Gram-negative thigh co-infections, brain infection, Klebsiella pneumonia, and mice undergoing immunosuppressive chemotherapy. This technique rapidly and specifically localized infections due to Enterobacteriaceae, providing a three-dimensional holistic view within the animal. Last, 18F-FDS PET monitored the efficacy of antimicrobial treatment, demonstrating a PET signal proportionate to the bacterial burden. Therapeutic failures associated with multidrug-resistant, extended-spectrum β-lactamase (ESBL)–producing E. coli infections were detected in real time. Together, these data show that 18F-FDS is a candidate imaging probe for translation to human clinical cases of known or suspected infections owing to Enterobacteriaceae. PMID:25338757
Using positron emission tomography to study human ketone body metabolism: a review.
Bouteldja, Nadia; Andersen, Lone Thing; Møller, Niels; Gormsen, Lars Christian
Ketone bodies - 3-hydroxybutyrate and acetoacetate - are important fuel substrates, which can be oxidized by most tissues in the body. They are synthesized in the liver and are derived from fatty acids released from adipose tissue. Intriguingly, under conditions of stress such as fasting, arterio-venous catheterization studies have shown that the brain switches from the use of almost 100% glucose to the use of >50-60% ketone bodies. A similar adaptive mechanism is observed in the heart, where fasting induces a shift toward ketone body uptake that provides the myocardium with an alternate fuel source and also favorably affects myocardial contractility. Within the past years there has been a renewed interest in ketone bodies and the possible beneficial effects of fasting/semi-fasting/exercising and other "ketogenic" regimens have received much attention. In this perspective, it is promising that positron emission tomography (PET) techniques with isotopically labeled ketone bodies, fatty acids and glucose offer an opportunity to study interactions between ketone body, fatty acid and glucose metabolism in tissues such as the brain and heart. PET scans are non-invasive and thus eliminates the need to place catheters in vascular territories not easily accessible. The short half-life of e.g. 11C-labeled PET tracers even allows multiple scans on the same study day and reduces the total radiation burden associated with the procedure. This short review aims to give an overview of current knowledge on ketone body metabolism obtained by PET studies and discusses the methodological challenges and perspectives involved in PET ketone body research. PMID:25195069
Quantitative Assessment of Radionuclide Uptake and Positron Emission Tomography-computed Tomography Image Contrast
Francis, Hasford; Amuasi, John Humphrey; Kwame, Kyere Augustine; Vangu, Mboyo Di Tamba
Radionuclide uptake and contrast for positron emission tomography-computed tomography (PET-CT) images have been assessed in this study using NEMA image quality phantom filled with background activity concentration of 5.3 kBq/mL fluorodeoxyglucose (F-18 FDG). Spheres in the phantom were filled in turns with water to mimic cold lesions and FDG of higher activity concentrations to mimic tumor sites. Transaxial image slices were acquired on the PET-CT system and used for the evaluation of mean standard uptake value (SUVmean) and contrasts for varying sphere sizes at different activity concentrations of 10.6 kBq/mL, 21.2 kBq/mL, and 42.4 kBq/mL. For spheres of same sizes, SUVmean increased with increase in activity concentration. SUVmean was increased by 80.6%, 83.5%, 63.2%, 87.4%, and 63.2% when activity concentrations of spheres with a diameter of 1.3 cm, 1.7 cm, 2.2 cm, 2.8 cm, and 3.7 cm, respectively, were increased from 10.6 kBq/mL to 42.4 kBq/mL. Average percentage contrast between cold spheres (cold lesions) and background activity concentration was estimated to be 89.96% for the spheres. Average contrast for the spheres containing 10.6 kBq/mL, 21.2 kBq/mL, and 42.4 kBq/mL were found to be 110.92%, 134.48%, and 150.52%, respectively. The average background contrast variability was estimated to be 2.97% at 95% confidence interval (P < 0.05). PMID:27650938
Four-Dimensional Positron Emission Tomography: Implications for Dose Painting of High-Uptake Regions
Aristophanous, Michalis; Killoran, Joseph H.; Chen, Aileen B.; Berbeco, Ross I.
Purpose: To investigate the behavior of tumor subvolumes of high [18F]-fluorodeoxyglucose (FDG) uptake as seen on clinical four-dimensional (4D) FDG-positron emission tomography (PET) scans. Methods and Materials: Four-dimensional FDG-PET/computed tomography scans from 13 patients taken before radiotherapy were available. The analysis was focused on regions of high uptake that are potential dose-painting targets. A total of 17 lesions (primary tumors and lymph nodes) were analyzed. On each one of the five phases of the 4D scan a classification algorithm was applied to obtain the region of highest uptake and segment the tumor volume. We looked at the behavior of both the high-uptake subvolume, called 'Boost,' and the segmented tumor volume, called 'Target.' We measured several quantities that characterize the Target and Boost volumes and quantified correlations between them. Results: The behavior of the Target could not always predict the behavior of the Boost. The shape deformation of the Boost regions was on average 133% higher than that of the Target. The gross to internal target volume expansion was on average 27.4% for the Target and 64% for the Boost, a statistically significant difference (p < 0.05). Finally, the inhale-to-exhale phase (20%) had the highest shape deformation for the Boost regions. Conclusions: A complex relationship between the measured quantities for the Boost and Target volumes is revealed. The results suggest that in cases in which advanced therapy techniques such as dose painting are being used, a close examination of the 4D PET scan should be performed.
Pre-clinical Positron Emission Tomography Reconstruction Algorithm Effect on Cu-64 ATSM Lesion Hypoxia
Sanghera, Bal; Wood, Katie; Sonoda, Luke I; Gogbashian, Andrew; Lowe, Gerry; Nunes, Andre; Stirling, James; Shepherd, Chris; Beynon, Gwen; Wong, Wai Lup
Objective: Application of distinct positron emission tomography (PET) scan reconstruction algorithms can lead to statistically significant differences in measuring lesion functional properties. We looked at the influence of two-dimensional filtered back projection (2D FBP), two-dimensional ordered subset expectation maximization (2D OSEM), three-dimensional ordered subset expectation maximization (3D OSEM) without 3D maximum a posteriori and with (3D OSEM MAP) on lesion hypoxia tracer uptake using a pre-clinical PET scanner. Methods: Reconstructed images of a rodent tumor model bearing P22 carcinosarcoma injected with hypoxia tracer Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) (i.e. Cu-64 ATSM) were analyzed at 10 minute intervals till 60 minute post injection. Lesion maximum standardized uptake values (SUVmax) and SUVmax/background SUVmean (T/B) were recorded and investigated after application of multiple algorithm and reconstruction parameters to assess their influence on Cu-64 ATSM measurements and associated trends over time. Results: SUVmaxSUVmax or T/B between 2D FBP, exhibited convergence for OSEM reconstructions while ANOVA results showed a significant difference in SUVmax or T/B between 2D FBP, 2D OSEM, 3D OSEM and 3D OSEM MAP reconstructions across all time frames. SUVmax and T/B were greatest in magnitude for 2D OSEM followed by 3D OSEM MAP, 3D OSEM and then 2D FBP at all time frames respectively. Similarly SUVmax and T/B standard deviations (SD) were lowest for 2D OSEM in comparison with other algorithms. Conclusion: Significantly higher magnitude lesion SUVmax and T/B combined with lower SD were observed using 2D OSEM reconstruction in comparison with 2D FBP, 3D OSEM and 3D OSEM MAP algorithms at all time frames. Results are SUVmax or T/B between 2D FBP, consistent with other published studies however more specimens are required for full validation. PMID:27299284
Importance of Defect Detectability in Positron Emission Tomography Imaging of Abdominal Lesions
Yamashita, Shozo; Yokoyama, Kunihiko; Onoguchi, Masahisa; Yamamoto, Haruki; Nakaichi, Tetsu; Tsuji, Shiro; Nakajima, Kenichi
Objective(s): This study was designed to assess defect detectability in positron emission tomography (PET) imaging of abdominal lesions. Methods: A National Electrical Manufactures Association International Electrotechnical Commission phantom was used. The simulated abdominal lesion was scanned for 10 min using dynamic list-mode acquisition method. Images, acquired with scan duration of 1-10 min, were reconstructed using VUE point HD and a 4.7 mm full-width at half-maximum (FWHM) Gaussian filter. Iteration-subset combinations of 2-16 and 2-32 were used. Visual and physical analyses were performed using the acquired images. To sequentially evaluate defect detectability in clinical settings, we examined two middle-aged male subjects. One had a liver cyst (approximately 10 mm in diameter) and the other suffered from pancreatic cancer with an inner defect region (approximately 9 mm in diameter). Results: In the phantom study, at least 6 and 3 min acquisition durations were required to visualize 10 and 13 mm defect spheres, respectively. On the other hand, spheres with diameters ≥17 mm could be detected even if the acquisition duration was only 1 min. The visual scores were significantly correlated with background (BG) variability. In clinical settings, the liver cyst could be slightly visualized with an acquisition duration of 6 min, although image quality was suboptimal. For pancreatic cancer, the acquisition duration of 3 min was insufficient to clearly describe the defect region. Conclusion: The improvement of BG variability is the most important factor for enhancing lesion detection. Our clinical scan duration (3 min/bed) may not be suitable for the detection of small lesions or accurate tumor delineation since an acquisition duration of at least 6 min is required to visualize 10 mm lesions, regardless of reconstruction parameters. Improvements in defect detectability are important for radiation treatment planning and accurate PET-based diagnosis. PMID:27408887
Quantitative Assessment of Radionuclide Uptake and Positron Emission Tomography-computed Tomography Image Contrast
Francis, Hasford; Amuasi, John Humphrey; Kwame, Kyere Augustine; Vangu, Mboyo Di Tamba
Radionuclide uptake and contrast for positron emission tomography-computed tomography (PET-CT) images have been assessed in this study using NEMA image quality phantom filled with background activity concentration of 5.3 kBq/mL fluorodeoxyglucose (F-18 FDG). Spheres in the phantom were filled in turns with water to mimic cold lesions and FDG of higher activity concentrations to mimic tumor sites. Transaxial image slices were acquired on the PET-CT system and used for the evaluation of mean standard uptake value (SUVmean) and contrasts for varying sphere sizes at different activity concentrations of 10.6 kBq/mL, 21.2 kBq/mL, and 42.4 kBq/mL. For spheres of same sizes, SUVmean increased with increase in activity concentration. SUVmean was increased by 80.6%, 83.5%, 63.2%, 87.4%, and 63.2% when activity concentrations of spheres with a diameter of 1.3 cm, 1.7 cm, 2.2 cm, 2.8 cm, and 3.7 cm, respectively, were increased from 10.6 kBq/mL to 42.4 kBq/mL. Average percentage contrast between cold spheres (cold lesions) and background activity concentration was estimated to be 89.96% for the spheres. Average contrast for the spheres containing 10.6 kBq/mL, 21.2 kBq/mL, and 42.4 kBq/mL were found to be 110.92%, 134.48%, and 150.52%, respectively. The average background contrast variability was estimated to be 2.97% at 95% confidence interval (P < 0.05).
In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography
Francis, D L; Freeman, A; Visvikis, D; Costa, D C; Luthra, S K; Novelli, M; Taylor, I; Ell, P J
Background and aims: Positron emission tomography (PET) using 18F labelled 2-fluoro-2-deoxy-D-glucose (18FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3′-deoxy-3-fluorothymidine (18FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of 18FLT and 18FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC). Patients and methods: Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54–87), were evaluated. Patients underwent 18FDG and 18FLT PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells). Results: Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both 18FLT and 18FDG. Three of the five resected liver metastases were also avid for 18FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of 18FLT had correspondingly very low proliferation. There was a statistically significant positive correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with 18FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with 18FDG avid lesions (r =0.4). Conclusions: 18FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy. PMID
Digital contrast enhancement of 18Fluorine-fluorodeoxyglucose positron emission tomography images in hepatocellular carcinoma
Pandey, Anil Kumar; Sharma, Sanjay Kumar; Agarwal, Krishan Kant; Sharma, Punit; Bal, Chandrasekhar; Kumar, Rakesh
Purpose: The role of 18fluorodeoxyglucose positron emission tomography (PET) is limited for detection of primary hepatocellular carcinoma (HCC) due to low contrast to the tumor, and normal hepatocytes (background). The aim of the present study was to improve the contrast between the tumor and background by standardizing the input parameters of a digital contrast enhancement technique. Materials and Methods: A transverse slice of PET image was adjusted for the best possible contrast, and saved in JPEG 2000 format. We processed this image with a contrast enhancement technique using 847 possible combinations of input parameters (threshold "m" and slope "e"). The input parameters which resulted in an image having a high value of 2nd order entropy, and edge content, and low value of absolute mean brightness error, and saturation evaluation metrics, were considered as standardized input parameters. The same process was repeated for total nine PET-computed tomography studies, thus analyzing 7623 images. Results: The selected digital contrast enhancement technique increased the contrast between the HCC tumor and background. In seven out of nine images, the standardized input parameters "m" had values between 150 and 160, and for other two images values were 138 and 175, respectively. The value of slope "e" was 4 in 4 images, 3 in 3 images and 1 in 2 images. It was found that it is important to optimize the input parameters for the best possible contrast for each image; a particular value was not sufficient for all the HCC images. Conclusion: The use of above digital contrast enhancement technique improves the tumor to background ratio in PET images of HCC and appears to be useful. Further clinical validation of this finding is warranted. PMID:26917889
Molecular imaging of atherosclerotic lesions by positron emission tomography - can it meet the expectations?
Brammen, Lindsay; Steiner, Sabine; Berent, Robert; Sinzinger, Helmut
Early non-invasive imaging of atherosclerosis and in particular the detection of lesions at risk with high specificity could significantly affect cardiovascular morbidity and mortality. Conventional nuclear medicine approaches, in particular using autologous radiolabeled lipoproteins, can be related to histopathological findings; however, they fail to identify lesions at risk. Positron emission tomography (PET) tracers with much better physical properties have been examined, the most detailed information being available for F-18-deoxyglucose (FDG) and F-18-sodium fluoride (NaF). These two approaches are sensitive to different biochemical mechanisms, i.e. inflammation and microcalcification. Initial enthusiasm, in particular for F-18-FDG, has disappeared, although for F-18-NaF there is some hope, but this is not a breakthrough. No tracer is available so far that is able to identify a specific characteristic of a lesion prone to rupture. Other PET tracers in the pipeline have been examined, mainly in experimental models and only a few in patients, but they failed to contribute significantly to early lesion discovery and do not support great expectations. The key question is: Do we understand what we see? Moreover, methodological problems, a lack of standardization of imaging protocols and aspects of quantification provide a wide range for potential future improvements. While monitoring a therapeutic intervention seems to be possible for both F-18-FDG and F-18-NaF, highly specific early identification of lesions at risk by PET imaging is still far away. As of today, PET is not ready for routine clinical judgment of atherosclerotic lesions at risk to rupture. Even if all these problems can be solved, radiation exposure will still remain a concern, in particular for repeated studies.
Determination of plasma protein binding of positron emission tomography radioligands by high-performance frontal analysis.
Amini, Nahid; Nakao, Ryuji; Schou, Magnus; Halldin, Christer
Positron emission tomography (PET) is an imaging technique based on the use of radioligands labeled with short lived radionuclides, such as (11)C (t½=20.4min) and (18)F (t½=109.8min), which as a consequence often requires rapid plasma protein binding analysis methods. In addition, PET radioligands can suffer from non-specific binding to the membrane when ultrafiltraion, which is the most commonly used method for measuring protein binding in PET, is employed. In this study a high-performance frontal analysis (HPFA) method based on incorporation of a gel filtration column (discovery(®) BIO GFC 100, 50mm×4.6mm, 5μm, 100Å) into a radio-LC system with phosphate buffered saline (PBS, pH 7.4) at a flow rate of 3ml/min as mobile phase was developed and investigated for four PET radioligands. The minimum injection volume (MIV) of plasma, which is a crucial factor in HPFA, was determined to be 200μl (human), 500μl (monkey), 700μl (human) and 1000μl (monkey) for these four radioligands. The MIV values increased as a higher fraction of the radioligand was present in the protein-free form. The protein binding results obtained were in good agreement with ultrafiltration and the method did not suffer from non-specific binding. The short analysis time (<12min) allowed multiple protein binding measurements during time course of a human [(11)C]PBR28 PET study. PMID:24922085
Accurate Automatic Delineation of Heterogeneous Functional Volumes in Positron Emission Tomography for Oncology Applications
Hatt, Mathieu; Cheze le Rest, Catherine; Descourt, Patrice; Dekker, Andre; De Ruysscher, Dirk; Oellers, Michel; Lambin, Philippe; Pradier, Olivier; Visvikis, Dimitris
Purpose: Accurate contouring of positron emission tomography (PET) functional volumes is now considered crucial in image-guided radiotherapy and other oncology applications because the use of functional imaging allows for biological target definition. In addition, the definition of variable uptake regions within the tumor itself may facilitate dose painting for dosimetry optimization. Methods and Materials: Current state-of-the-art algorithms for functional volume segmentation use adaptive thresholding. We developed an approach called fuzzy locally adaptive Bayesian (FLAB), validated on homogeneous objects, and then improved it by allowing the use of up to three tumor classes for the delineation of inhomogeneous tumors (3-FLAB). Simulated and real tumors with histology data containing homogeneous and heterogeneous activity distributions were used to assess the algorithm's accuracy. Results: The new 3-FLAB algorithm is able to extract the overall tumor from the background tissues and delineate variable uptake regions within the tumors, with higher accuracy and robustness compared with adaptive threshold (T{sub bckg}) and fuzzy C-means (FCM). 3-FLAB performed with a mean classification error of less than 9% +- 8% on the simulated tumors, whereas binary-only implementation led to errors of 15% +- 11%. T{sub bckg} and FCM led to mean errors of 20% +- 12% and 17% +- 14%, respectively. 3-FLAB also led to more robust estimation of the maximum diameters of tumors with histology measurements, with <6% standard deviation, whereas binary FLAB, T{sub bckg} and FCM lead to 10%, 12%, and 13%, respectively. Conclusion: These encouraging results warrant further investigation in future studies that will investigate the impact of 3-FLAB in radiotherapy treatment planning, diagnosis, and therapy response evaluation.
Molecular imaging of atherosclerotic lesions by positron emission tomography - can it meet the expectations?
Brammen, Lindsay; Steiner, Sabine; Berent, Robert; Sinzinger, Helmut
Early non-invasive imaging of atherosclerosis and in particular the detection of lesions at risk with high specificity could significantly affect cardiovascular morbidity and mortality. Conventional nuclear medicine approaches, in particular using autologous radiolabeled lipoproteins, can be related to histopathological findings; however, they fail to identify lesions at risk. Positron emission tomography (PET) tracers with much better physical properties have been examined, the most detailed information being available for F-18-deoxyglucose (FDG) and F-18-sodium fluoride (NaF). These two approaches are sensitive to different biochemical mechanisms, i.e. inflammation and microcalcification. Initial enthusiasm, in particular for F-18-FDG, has disappeared, although for F-18-NaF there is some hope, but this is not a breakthrough. No tracer is available so far that is able to identify a specific characteristic of a lesion prone to rupture. Other PET tracers in the pipeline have been examined, mainly in experimental models and only a few in patients, but they failed to contribute significantly to early lesion discovery and do not support great expectations. The key question is: Do we understand what we see? Moreover, methodological problems, a lack of standardization of imaging protocols and aspects of quantification provide a wide range for potential future improvements. While monitoring a therapeutic intervention seems to be possible for both F-18-FDG and F-18-NaF, highly specific early identification of lesions at risk by PET imaging is still far away. As of today, PET is not ready for routine clinical judgment of atherosclerotic lesions at risk to rupture. Even if all these problems can be solved, radiation exposure will still remain a concern, in particular for repeated studies. PMID:27058798
Relationship of computed tomography perfusion and positron emission tomography to tumour progression in malignant glioma
Yeung, Timothy P C; Yartsev, Slav; Lee, Ting-Yim; Wong, Eugene; He, Wenqing; Fisher, Barbara; VanderSpek, Lauren L; Macdonald, David; Bauman, Glenn
Introduction: This study aimed to explore the potential for computed tomography (CT) perfusion and 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting sites of future progressive tumour on a voxel-by-voxel basis after radiotherapy and chemotherapy. Methods: Ten patients underwent pre-radiotherapy magnetic resonance (MR), FDG-PET and CT perfusion near the end of radiotherapy and repeated post-radiotherapy follow-up MR scans. The relationships between these images and tumour progression were assessed using logistic regression. Cross-validation with receiver operating characteristic (ROC) analysis was used to assess the value of these images in predicting sites of tumour progression. Results: Pre-radiotherapy MR-defined gross tumour; near-end-of-radiotherapy CT-defined enhancing lesion; CT perfusion blood flow (BF), blood volume (BV) and permeability-surface area (PS) product; FDG-PET standard uptake value (SUV); and SUV:BF showed significant associations with tumour progression on follow-up MR imaging (P < 0.0001). The mean sensitivity (±standard deviation), specificity and area under the ROC curve (AUC) of PS were 0.64 ± 0.15, 0.74 ± 0.07 and 0.72 ± 0.12 respectively. This mean AUC was higher than that of the pre-radiotherapy MR-defined gross tumour and near-end-of-radiotherapy CT-defined enhancing lesion (both AUCs = 0.6 ± 0.1, P ≤ 0.03). The multivariate model using BF, BV, PS and SUV had a mean AUC of 0.8 ± 0.1, but this was not significantly higher than the PS only model. Conclusion: PS is the single best predictor of tumour progression when compared to other parameters, but voxel-based prediction based on logistic regression had modest sensitivity and specificity.
EndoTOFPET-US - A Miniaturised Calorimeter for Endoscopic Time-of-Flight Positron Emission Tomography
NASA Astrophysics Data System (ADS)
Zvolský, Milan; EndoTOFPET-US Collaboration
In the scope of the EndoTOFPET-US project, a novel multimodal device for Ultrasound (US) Endoscopy and Positron Emission Tomography (PET) is being developed. The project aims at detecting and quantifying morphologic and functional markers and developing new biomarkers for pancreas and prostate oncology. Exploiting the Time-of-Flight (TOF) information of the gamma rays allows for a more sensitive, more precise and lower radiation- dose imaging and intervention on small internal structures. The detection of the gamma rays is realised with the help of scintillator crystals with Silicon Photomultiplier (SiPM) read-out, aiming at a coincidence time resolution of 200 ps and a spatial resolution of ≈ 1 mm. For the endoscopic detector, digital SiPMs are utilised for the first time in an instrument planned for clinical applications. The functionality of the instrument as well as the challenges that accompany the high miniaturisation of the endoscopic detector and the asymmetric and variable geometry of the system, are presented. The demands on the system involve the fields of scintillating crystallography, ultra-fast photon detection, highly integrated electronics, system integration as well as image reconstruction. The single detector components have been fully characterised and are performing up to specifications. Two dedicated ASIC chips have been developed for the project. The first PET images have been acquired with a test setup that consists solely of hardware and software developed within the collaboration and demonstrate that the data acquisition and reconstruction chain is operational. In this talk, the characterisation of the single components and the status of the detector integration and comissioning is presented.
Elevated Brain Cannabinoid CB1 Receptor Availability in Posttraumatic Stress Disorder: A Positron Emission Tomography Study
Neumeister, Alexander; Normandin, Marc D.; Pietrzak, Robert H.; Piomelli, Daniele; Zheng, Ming-Qiang; Gujarro-Anton, Ana; Potenza, Marc N.; Bailey, Christopher R.; Lin, Shu-fei; Najafzadeh, Soheila; Ropchan, Jim; Henry, Shannan; Corsi-Travali, Stefani; Carson, Richard E.; Huang, Yiyun
Endocannabinoids and their attending cannabinoid type 1 receptor (CB1) have been implicated in animal models of posttraumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [11C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma controls [TC]) and those without such histories (healthy controls [HC]). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance (MR) imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [11C]OMAR, which measures volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [11C]OMAR VT values (F(2,53)=7.96, p=.001; 19.5% and 14.5% higher, respectively) which were most pronounced in women (F(1,53)=5.52, p=.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively—OMAR VT, anandamide, and cortisol—correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder. PMID:23670490
Quantitative Assessment of Radionuclide Uptake and Positron Emission Tomography-computed Tomography Image Contrast.
Francis, Hasford; Amuasi, John Humphrey; Kwame, Kyere Augustine; Vangu, Mboyo Di Tamba
Radionuclide uptake and contrast for positron emission tomography-computed tomography (PET-CT) images have been assessed in this study using NEMA image quality phantom filled with background activity concentration of 5.3 kBq/mL fluorodeoxyglucose (F-18 FDG). Spheres in the phantom were filled in turns with water to mimic cold lesions and FDG of higher activity concentrations to mimic tumor sites. Transaxial image slices were acquired on the PET-CT system and used for the evaluation of mean standard uptake value (SUVmean) and contrasts for varying sphere sizes at different activity concentrations of 10.6 kBq/mL, 21.2 kBq/mL, and 42.4 kBq/mL. For spheres of same sizes, SUVmean increased with increase in activity concentration. SUVmean was increased by 80.6%, 83.5%, 63.2%, 87.4%, and 63.2% when activity concentrations of spheres with a diameter of 1.3 cm, 1.7 cm, 2.2 cm, 2.8 cm, and 3.7 cm, respectively, were increased from 10.6 kBq/mL to 42.4 kBq/mL. Average percentage contrast between cold spheres (cold lesions) and background activity concentration was estimated to be 89.96% for the spheres. Average contrast for the spheres containing 10.6 kBq/mL, 21.2 kBq/mL, and 42.4 kBq/mL were found to be 110.92%, 134.48%, and 150.52%, respectively. The average background contrast variability was estimated to be 2.97% at 95% confidence interval (P < 0.05). PMID:27650938
Effects of amphetamine on the human brain opioid system--a positron emission tomography study.
Guterstam, Joar; Jayaram-Lindström, Nitya; Cervenka, Simon; Frost, J James; Farde, Lars; Halldin, Christer; Franck, Johan
Studies in rodents have shown that psychostimulant drugs such as cocaine and amphetamine cause endorphin release in the brain reward system. There is also evidence for the involvement of the opioid system in human psychostimulant dependence. The acute effects of an i.v. psychostimulant drug on the brain opioid system, however, have not yet been investigated in humans. We hypothesized that an i.v. dose of amphetamine as compared to placebo would cause an opioid release in the human brain reward system, measurable as a reduction of the binding potential of the μ-opioid receptor radioligand [(11)C]carfentanil. Ten healthy young men were examined using positron emission tomography (PET) and [(11)C]carfentanil in three sessions: at baseline; after placebo; after an i.v. amphetamine dose of 0.3 mg/kg bodyweight. The order of amphetamine and placebo was double-blinded and randomized. PET examinations were performed with a Siemens high resolution research tomograph. Data were analysed with the simplified reference tissue model, applying manually drawn regions of interest for every subject. Using repeated measures analysis of variance, we found no significant differences in [(11)C]carfentanil binding potential between amphetamine and placebo conditions in any of the investigated brain regions. In contrast to data from rodent studies and a recent study of oral amphetamine administration in humans, an i.v. dose of amphetamine does not cause any acute opioid release in healthy human subjects. The postulated role of the opioid system in mediating the effects of amphetamine needs to be further investigated in animal models of the disease as well as in patient populations.
Respiratory gating in positron emission tomography: A quantitative comparison of different gating schemes
Dawood, Mohammad; Buether, Florian; Lang, Norbert; Schober, Otmar; Schaefers, Klaus P
Respiratory gating is used for reducing the effects of breathing motion in a wide range of applications from radiotherapy treatment to diagnostical imaging. Different methods are feasible for respiratory gating. In this study seven gating methods were developed and tested on positron emission tomography (PET) listmode data. The results of seven patient studies were compared quantitatively with respect to motion and noise. (1) Equal and (2) variable time-based gating methods use only the time information of the breathing cycle to define respiratory gates. (3) Equal and (4) variable amplitude-based gating approaches utilize the amplitude of the respiratory signal. (5) Cycle-based amplitude gating is a combination of time and amplitude-based techniques. A baseline correction was applied to methods (3) and (4) resulting in two new approaches: Baseline corrected (6) equal and (7) variable amplitude-based gating. Listmode PET data from seven patients were acquired together with a respiratory signal. Images were reconstructed applying the seven gating methods. Two parameters were used to quantify the results: Motion was measured as the displacement of the heart due to respiration and noise was defined as the standard deviation of pixel intensities in a background region. The amplitude-based approaches (3) and (4) were superior to the time-based methods (1) and (2). The improvement in capturing the motion was more than 30% (up to 130%) in all subjects. The variable time (2) and amplitude (4) methods had a more uniform noise distribution among all respiratory gates compared to equal time (1) and amplitude (3) methods. Baseline correction did not improve the results. Out of seven different respiratory gating approaches, the variable amplitude method (4) captures the respiratory motion best while keeping a constant noise level among all respiratory phases.
Glycine transporter type 1 occupancy by bitopertin: a positron emission tomography study in healthy volunteers.
Martin-Facklam, Meret; Pizzagalli, Flavia; Zhou, Yun; Ostrowitzki, Susanne; Raymont, Vanessa; Brašić, James R; Parkar, Nikhat; Umbricht, Daniel; Dannals, Robert F; Goldwater, Ron; Wong, Dean F
Deficient N-methyl-D-aspartate (NMDA) receptor transmission is thought to underlie schizophrenia. An approach for normalizing glutamate neurotransmission by enhancing NMDA receptor transmission is to increase glycine availability by inhibiting the glycine transporter type 1 (GlyT1). This study investigated the relationship between the plasma concentration of the glycine reuptake inhibitor bitopertin (RG1678) and brain GlyT1 occupancy. Healthy male volunteers received up to 175 mg bitopertin once daily, for 10-12 days. Three positron emission tomography scans, preceded by a single intravenous infusion of ∼30 mCi [(11)C]RO5013853, were performed: at baseline, on the last day of bitopertin treatment, and 2 days after drug discontinuation. Eighteen subjects were enrolled. At baseline, regional volume of distribution (V(T)) values were highest in the pons, thalamus, and cerebellum (1.7-2.7 ml/cm(3)) and lowest in cortical areas (∼0.8 ml/cm(3)). V(T) values were reduced to a homogeneous level following administration of 175 mg bitopertin. Occupancy values derived by a two-tissue five-parameter (2T5P) model, a simplified reference tissue model (SRTM), and a pseudoreference tissue model (PRTM) were overall comparable. At steady state, the relationship between bitopertin plasma concentration and GlyT1 occupancy derived by the 2T5P model, SRTM, and PRTM exhibited an EC(50) of ∼190, ∼200, and ∼130 ng/ml, respectively. E(max) was ∼92% independently of the model used. Bitopertin plasma concentration was a reliable predictor of occupancy because the concentration-occupancy relationship was superimposable at steady state and 2 days after drug discontinuation. These data allow understanding of the concentration-occupancy-efficacy relationship of bitopertin and support dose selection of future molecules. PMID:23132267
Positron emission tomography for initial staging of esophageal cancer among medicare beneficiaries
Varghese, Thomas K.; Flanagan, Meghan R.; Flum, David R.; Shankaran, Veena; Oelschlager, Brant K.; Mulligan, Michael S.; Wood, Douglas E.; Pellegrini, Carlos A.
Background The role of positron emission tomography (PET) in the initial staging of esophageal cancer is to detect occult metastases, but its ability to do so has not been evaluated at the population-level. In 2001, Medicare approved reimbursement of PET for esophageal cancer staging. We hypothesized rapid adoption of PET after 2001 and a coincident increase in the prevalence of stage IV disease. Methods A retrospective cohort study [1997-2009] was conducted of 12,870 Medicare beneficiaries with esophageal cancer using the Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Results PET use increased from <3% before 2001 to 44% in 2009 (post-PET era) (P trend <0.001). Over the same period, the prevalence of stage IV disease also increased (20% in 1997 and 28% in 2009, P trend <0.001). After adjusting for changing patient characteristics over time, the rate of increase in stage IV disease in the post-PET era [relative risk (RR) =1.06; 95% confidence interval (CI), 1.00-1.13] was no different than the rate of increase in the pre-PET era (RR =1.02; 95% CI, 1.02-1.04). Over the entire study period, the prevalence of unrecorded stage decreased by more than half (43% to 18%, adjusted P trend <0.001) with coincident increases in stage 0-III (37% to 53%, adjusted P trend <0.001) as well as stage IV disease. Conclusions The increasing frequency of PET use and stage IV disease over time is more likely explained by improved documentation rather than PET's ability to detect occult metastases. The absence of compelling population-level impact compliments previous studies, revealing an opportunity to increase value through selective use of PET. PMID:27284472
Positron emission tomography (PET) for assessing aerosol deposition of orally inhaled drug products.
Dolovich, Myrna B; Bailey, Dale L
The topical distribution of inhaled therapies in the lung can be viewed using radionuclides and imaging. Positron emission tomography (PET) is a three-dimensional functional imaging technique providing quantitatively accurate localization of the quantity and distribution of an inhaled or injected PET radiotracer in the lung. A series of transaxial slices through the lungs are obtained, comparable to an X-ray computed tomography (CT) scan. Subsequent reformatting allows coronal and sagittal images of the distribution of radioactivity to be viewed. This article describes procedures for administering [(18)F]-fluorodeoxyglucose aerosol to human subjects for the purpose of determining dose and distribution following inhalation from an aerosol drug delivery device (ADDD). The advantages of using direct-labeled PET drugs in the ADDD are discussed with reference to the literature. The methods for designing the inhalation system, determining proper radiation shielding, calibration, and validation of administered radioactivity, scanner setup, and data handling procedures are described. Obtaining an X-ray CT or radionuclide transmission scan to provide accurate geometry of the lung and also correct for tissue attenuation of the PET radiotracer is discussed. Protocols for producing accurate images, including factors that need to be incorporated into the data calibration, are described, as well as a proposed standard method for partitioning the lung into regions of interest. Alternate methods are described for more detailed assessments. Radiation dosimetry/risk calculations for the procedures are appended, as well as a sample data collection form and spreadsheet for calculations. This article should provide guidance for those interested in using PET to determine quantity and distribution of inhaled therapeutics. PMID:23215847
Enhancement of positron emission tomography-computed tomography image quality using the principle of stochastic resonance
Pandey, Anil Kumar; Sharma, Sanjay Kumar; Sharma, Punit; Singh, Harmandeep; Patel, Chetan; Sarkar, Kaushik; Kumar, Rakesh; Bal, Chandra Sekhar
Purpose: Acquisition of higher counts improves visual perception of positron emission tomography-computed tomography (PET-CT) image. Larger radiopharmaceutical doses (implies more radiation dose) are administered to acquire this count in a short time period. However, diagnostic information does not increase after a certain threshold of counts. This study was conducted to develop a post processing method based on principle of "stochastic resonance" to improve visual perception of the PET-CT image having a required threshold counts. Materials and Methods: PET-CT images (JPEG file format) with low, medium, and high counts in the image were included in this study. The image was corrupted with the addition of Poisson noise. The amplitude of the Poisson noise was adjusted by dividing each pixel by a constant 1, 2, 4, 8, 16, and 32. The best amplitude of the noise that gave best images quality was selected based on high value of entropy of the output image, high value of structural similarity index and feature similarity index. Visual perception of the image was evaluated by two nuclear medicine physicians. Results: The variation in structural and feature similarity of the image was not appreciable visually, but statistically images deteriorated as the noise amplitude increases although maintaining structural (above 70%) and feature (above 80%) similarity of input images in all cases. We obtained the best image quality at noise amplitude "4" in which 88% structural and 95% feature similarity of the input images was retained. Conclusion: This method of stochastic resonance can be used to improve the visual perception of the PET-CT image. This can indirectly lead to reduction of radiation dose. PMID:25400362
Role of (18F) 2-fluoro-2-deoxyglucose positron emission tomography in upper gastrointestinal malignancies
Smyth, Elizabeth C; Shah, Manish A
The role of whole-body FDG [(18F) 2-fluoro-2-deoxyglucose] positron emission tomography (PET) scanning as an imaging modality in the management of patients with malignancy has evolved enormously over the past two decades. FDG-PET has demonstrated significant efficacy in the staging, prognostication and detection of occult metastatic disease in malignancies of the gastrointestinal tract, in addition to assessment of the response to cytotoxic chemotherapy in a more timely manner than has traditionally been possible by more conventional imaging tools. The sensitivity and specificity of FDG-PET for the detection and staging of malignancy depend not only on the site and size of the primary tumor and metastases, but also on histological cell type, reflecting underlying disparities in glucose metabolism. The metabolic response to neo-adjuvant chemotherapy or to chemo-radiotherapy in cancers of the gastro-esophageal junction or stomach has been demonstrated in several prospective studies to correlate significantly with both the histological tumor response to treatment and with consequent improvements in overall survival. This may offer a future paradigm of personalized treatment based on the PET response to chemotherapy. FDG-PET has been less successful in efforts to screen for and detect recurrent upper gastrointestinal malignancies, and in the detection of low volume metastatic peritoneal disease. Efforts to improve the accuracy of PET include the use of novel radiotracers such as (18F) FLT (3-deoxy-3-fluorothymidine) or 11C-choline, or fusion PET-CT with concurrent high-resolution computed tomography. This review focuses on the role of FDG-PET scanning in staging and response assessment in malignancies of the upper gastrointestinal tract, specifically gastric, esophageal and pancreas carcinoma. PMID:22171140
A practical guide to the construction of radiometallated bioconjugates for positron emission tomography
Zeglis, Brian M.
Positron emission tomography (PET) has become a vital imaging modality in the diagnosis and treatment of disease, most notably cancer. A wide array of small molecule PET radiotracers have been developed that employ the short half-life radionuclides 11C, 13N, 15O, and 18F. However, PET radiopharmaceuticals based on biomolecular targeting vectors have been the subject of dramatically increased research in both the laboratory and the clinic. Typically based on antibodies, oligopeptides, or oligonucleotides, these tracers have longer biological half-lives than their small molecule counterparts and thus require labeling with radionuclides with longer, complementary radioactive half-lives, such as the metallic isotopes 64Cu, 68Ga, 86Y, and 89Zr. Each bioconjugate radiopharmaceutical has four component parts: biomolecular vector, radiometal, chelator, and covalent link between chelator and biomolecule. With the exception of the radiometal, a tremendous variety of choices exists for each of these pieces, and a plethora of different chelation, conjugation, and radiometallation strategies have been utilized to create agents ranging from 68Ga-labeled pentapeptides to 89Zr-labeled monoclonal antibodies. Herein, the authors present a practical guide to the construction of radiometal-based PET bioconjugates, in which the design choices and synthetic details of a wide range of biomolecular tracers from the literature are collected in a single reference. In assembling this information, the authors hope both to illuminate the diverse methods employed in the synthesis of these agents and also to create a useful reference for molecular imaging researchers both experienced and new to the field. PMID:21442098
Positron emission tomography as a diagnostic tool in infection: present role and future possibilities.
Basu, Sandip; Chryssikos, Timothy; Moghadam-Kia, Siamak; Zhuang, Hongming; Torigian, Drew A; Alavi, Abass
The past decade has witnessed the emergence of yet another promising application of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in the detection and management of patients with infection and inflammatory disorders. This phenomenon is quite evident when the peer-reviewed scientific literature is searched for on this topic. Among these scientific communications, the 6 conditions in which FDG-PET has demonstrated its greatest utility include (1) chronic osteomyelitis, (2) complicated lower-limb prostheses, (3) complicated diabetic foot, (4) fever of unknown origin, (5) acquired immunodeficiency syndrome (ie, AIDS), and (6) vascular graft infection and fistula. On the basis of published literature, orthopedic infections, particularly those related to implanted prostheses and osteomyelitis (including that occurring in the setting of a complicated diabetic foot), can be detected successfully by the use of FDG-PET and, therefore, this modality has great promise for becoming the study of choice in these complex settings. Increasingly, this technique is being used to detect infection in soft tissues, including those representing the sources of fever of unknown origin. The ability of FDG-PET to diagnose vascular graft infection and fistula, even when the anatomical imaging modalities are inconclusive, is of considerable interest to practitioners of vascular surgery. Combined PET/computed tomography (CT) imaging has the potential to determine the sites of infection or inflammation with high precision. The data on the role of PET/CT imaging in the assessment of infection and inflammation is sparse, but this combined modality approach may prove to be the study of choice in foreseeable future for precise localization of involved sites. However, the role of PET/CT may be limited in the presence of metallic artifacts (such as those caused by prostheses) adjacent to the sites of infection. PMID:19038599
Occupational Exposure to Veterinary Workers from the Positron Emission Tomography Imaging Agent 64Cu-ATSM.
Hetrick, Lucas D; Kraft, Susan L; Johnson, Thomas E
Cu-ATSM is an emerging radiopharmaceutical for diagnostic use in positron emission tomography (PET), but to date there are no studies that assess the potential occupational doses to workers in either human or veterinary medicine. This study was aimed at determining the external radiation dose to veterinary workers from clinical PET/CT (PET combined with computed tomography) procedures using Cu-ATSM. To determine the dose to the workers, each worker was assigned two Electronic Personal Dosimeters (EPDs) to be worn on the chest and waist during the entirety of each procedure. The workers monitored during this study included a radiobiologist, a nuclear medicine technologist, an anesthesiologist, and a veterinary surgeon. Seven canine patients were imaged with an average mass of 33.7 kg (a range of 20.0-55.1 kg) with an average injected activity of 5 MBq kg. The dose range for the radiobiologist was 2-17 μSv (mean of 7.1 μSv), for the nuclear medicine technologist 0-14 μSv (mean of 5.6 μSv), for the anesthesiologist 0-12 μSv (mean of 4.0 μSv), and for the surgeon 0-10 μSv (mean of 3.6 μSv). In a comparison between the results of this study and published literature on occupational exposures from veterinary FDG PET/CT procedures, Cu-ATSM veterinary PET/CT procedures, on a per patient bias, exposed workers to less radiation. PMID:26425985
Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms
McBride, O.M.B.; Joshi, N.V.; Robson, J.M.J.; MacGillivray, T.J.; Gray, C.D.; Fletcher, A.M.; Dweck, M.R.; van Beek, E.J.R.; Rudd, J.H.F.; Newby, D.E.; Semple, S.I.
Objectives Inflammation is critical in the pathogenesis of abdominal aortic aneurysm (AAA) disease. Combined 18F-fludeoxyglucose (18F-FDG) positron emission tomography with computed tomography (PET-CT) and ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) are non-invasive methods of assessing tissue inflammation. The aim of this study was to compare these techniques in patients with AAA. Materials and methods Fifteen patients with asymptomatic AAA with diameter 46 ± 7 mm underwent PET-CT with 18F-FDG, and T2*-weighted MRI before and 24 hours after administration of USPIO. The PET-CT and MRI data were then co-registered. Standardised uptake values (SUVs) were calculated to measure 18F-FDG activity, and USPIO uptake was determined using the change in R2*. Comparisons between the techniques were made using a quadrant analysis and a voxel-by-voxel evaluation. Results When all areas of the aneurysm were evaluated, there was a modest correlation between the SUV on PET-CT and the change in R2* on USPIO-enhanced MRI (n = 70,345 voxels; r = .30; p < .0001). Although regions of increased 18F-FDG and USPIO uptake co-localised on occasion, this was infrequent (kappa statistic 0.074; 95% CI 0.026–0.122). 18F-FDG activity was commonly focused in the shoulder region whereas USPIO uptake was more apparent in the main body of the aneurysm. Maximum SUV was lower in patients with mural USPIO uptake. Conclusions Both 18F-FDG PET-CT and USPIO-MRI uptake identify vascular inflammation associated with AAA. Although they demonstrate a modest correlation, there are distinct differences in the pattern and distribution of uptake, suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively. PMID:26919936
Positron emission tomography imaging of braintumors with Cobalt-55 and L-[1-C11]-tyrosine
Jansen, H.M.L.; Pruim J.; Willemsen, A.T.M.
The applicability of positron emission tomography (PET) with [C-11] tyrosine (TYR) and Cobalt-55 (Co) in patients with known primary brain tumors is reported. We used Co as a Calcium (Ca) marker to study Ca influx in degenerating neural tissue and TYR to indicate incorporation of amino acids into protein. Four patients showing a primary brain tumor with central necrosis on CT/MRI were studied with Co-PET. Additionally, 2 of these patients were consecutively studied with TYR-PET. Diagnostic confirmation was obtained by means of histology and/or cytology shortly after PET. Thirty-seven MBq Co was administered iv. approximately 24 hours before acquisition. The Co-scan was acquired for I hour. Immediately following Co-PET, 2 patients received 370 MBq TYR iv. TYR-PET acquisition was done dynamically for 55 minutes starting from the time of injection. The necrotic center of the tumor revealed no uptake of either Co or TYR. Vital tumor tissue showed intense uptake of TYR, indicating a high protein synthesis rate (PSR). The circumferent zone between necrotic and tumor tissue showed evident uptake of Co, suggesting cell-decay. In conclusion, TYR and Co are both suitable tracers for visualization of different aspects of brain malignancies, ie. PSR and cell-decay. Combining Co and TYR enables differentiation of necrosis vs. tumor growth with clear marking of the border zone. We think these complementary PET-techniques in conjunction with CT and/or MRI allow the visualization of different aspects of tumor tissue: central necrosis (CT/MRI), cell-decay (Co-PET) and vital tumor tissue (TYR-PET).
Development of an angled Si-PM-based detector unit for positron emission mammography (PEM) system
NASA Astrophysics Data System (ADS)
Nakanishi, Kouhei; Yamamoto, Seiichi
Positron emission mammography (PEM) systems have higher sensitivity than clinical whole body PET systems because they have a smaller ring diameter. However, the spatial resolution of PEM systems is not high enough to detect early stage breast cancer. To solve this problem, we developed a silicon photomultiplier (Si-PM) based detector unit for the development of a PEM system. Since a Si-PM's channel is small, Si-PM can resolve small scintillator pixels to improve the spatial resolution. Also Si-PM based detectors have inherently high timing resolution and are able to reduce the random coincidence events by reducing the time window. We used 1.5×1.9×15 mm LGSO scintillation pixels and arranged them in an 8×24 matrix to form scintillator blocks. Four scintillator blocks were optically coupled to Si-PM arrays with an angled light guide to form a detector unit. Since the light guide has angles of 5.625°, we can arrange 64 scintillator blocks in a nearly circular shape (a regular 64-sided polygon) using 16 detector units. We clearly resolved the pixels of the scintillator blocks in a 2-dimensional position histogram where the averages of the peak-to-valley ratios (P/Vs) were 3.7±0.3 and 5.7±0.8 in the transverse and axial directions, respectively. The average energy resolution was 14.2±2.1% full-width at half-maximum (FWHM). By including the temperature dependent gain control electronics, the photo-peak channel shifts were controlled within ±1.5% with the temperature from 23 °C to 28 °C. With these results, in addition to the potential high timing performance of Si-PM based detectors, our developed detector unit is promising for the development of a high-resolution PEM system.
Patient self-attenuation and technologist dose in positron emission tomography
Zeff, Benjamin W.; Yester, Michael V.
Positron emission tomography (PET), with 511-keV radiation and long patient-uptake times, presents unique radiation safety concerns. This two-part study considers aspects of PET radiation safety as they relate to PET suite design, dose to the public, and technologist occupational dose. In the first part of the study, the self-attenuation of radiation by patients' bodies was quantified. The radiation exposure was measured at three positions from 64 patients injected with fluorine-18 fluorodeoxyglucose (FDG) during the uptake period. Compared with an in vitro control used as a point source, a significant decrease in exposure (>40% at 1 m) was observed due to nonuniform distribution of FDG and attenuation within the patients. The attenuation data are consistent with results from simulations [M. E. Phelps, ''Comments and Perspectives,'' J. Nucl. Med. 45, 1601 (2004)] that treat the body as a uniform, water-filled cylinder. As distance is often the principal source of protection for 511-keV radiation, the considerable self-attenuation may allow for more compact PET suites. However, despite high patient self-attenuation, shielding, and standard precautionary measures, PET technologist occupational doses can remain quite high ({approx}12 mSv/year). The second part of this study tracked the daily dose received by PET technologists. Close technologist-patient interaction both during and following FDG administration, as much as 20 min/study, contribute to the high doses and point to the need for a more innovative approach to radiation protection for PET technologists.
Determination of elemental tissue composition following proton treatment using positron emission tomography
Cho, Jongmin; Ibbott, Geoffrey; Gillin, Michael; Gonzalez-Lepera, Carlos; Min, Chul Hee; Paganetti, Harald; Zhu, Xuping; El Fakhri, Georges; Mawlawi, Osama
Purpose Positron emission tomography (PET) has been suggested as an imaging technique for in vivo proton dose and range verification after proton induced-tissue activation. During proton treatment, irradiated tissue is activated and decays while emitting positrons. In this paper, we assessed the feasibility of using PET imaging after proton treatment to determine tissue elemental composition by evaluating the resultant composite decay curve of activated tissue. Methods A phantom consisting of sections composed of different combinations of 1H, 12C, 14N, and 16O was irradiated using a pristine Bragg peak and a 6-cm spread-out Bragg-peak (SOBP) proton beam. The beam ranges defined at 90% distal dose were 10 cm; the delivered dose was 1.6 Gy for the near monoenergetic beam and 2 Gy for the SOBP beam. After irradiation, activated phantom decay was measured using an in-room PET scanner for 30 minutes in list mode. Decay curves from the activated 12C and 16O sections were first decomposed into multiple simple exponential decay curves, each curve corresponding to a constituent radioisotope, using a least-squares method. The relative radioisotope fractions from each section were determined. These fractions were used to guide the decay curve decomposition from the section consisting mainly of 12C+16O and calculate the relative elemental composition of 12C and 16O. A Monte Carlo simulation was also used to determine the elemental composition of the 12C + 16O section. The calculated compositions of the 12C + 16O section using both approaches (PET and Monte Carlo) were compared with the true known phantom composition. Finally, 2 patients were imaged using an in-room PET scanner after proton therapy of the head. Their PET data and the technique described above were used to construct elemental composition (12C and 16O) maps that corresponded to the proton-activated regions. We compared the 12C and 16O compositions of 7 ROIs that corresponded to the vitreous humor, adipose
Determination of elemental tissue composition following proton treatment using positron emission tomography
NASA Astrophysics Data System (ADS)
Cho, Jongmin; Ibbott, Geoffrey; Gillin, Michael; Gonzalez-Lepera, Carlos; Min, Chul Hee; Zhu, Xuping; El Fakhri, Georges; Paganetti, Harald; Mawlawi, Osama
Positron emission tomography (PET) has been suggested as an imaging technique for in vivo proton dose and range verification after proton induced-tissue activation. During proton treatment, irradiated tissue is activated and decays while emitting positrons. In this paper, we assessed the feasibility of using PET imaging after proton treatment to determine tissue elemental composition by evaluating the resultant composite decay curve of activated tissue. A phantom consisting of sections composed of different combinations of 1H, 12C, 14N, and 16O was irradiated using a pristine Bragg peak and a 6 cm spread-out Bragg-peak (SOBP) proton beam. The beam ranges defined at 90% distal dose were 10 cm the delivered dose was 1.6 Gy for the near monoenergetic beam and 2 Gy for the SOBP beam. After irradiation, activated phantom decay was measured using an in-room PET scanner for 30 min in list mode. Decay curves from the activated 12C and 16O sections were first decomposed into multiple simple exponential decay curves, each curve corresponding to a constituent radioisotope, using a least-squares method. The relative radioisotope fractions from each section were determined. These fractions were used to guide the decay curve decomposition from the section consisting mainly of 12C + 16O and calculate the relative elemental composition of 12C and 16O. A Monte Carlo simulation was also used to determine the elemental composition of the 12C + 16O section. The calculated compositions of the 12C + 16O section using both approaches (PET and Monte Carlo) were compared with the true known phantom composition. Finally, two patients were imaged using an in-room PET scanner after proton therapy of the head. Their PET data and the technique described above were used to construct elemental composition (12C and 16O) maps that corresponded to the proton-activated regions. We compared the 12C and 16O compositions of seven ROIs that corresponded to the vitreous humor, adipose/face mask, adipose
Enhancing 18F uptake in a single particle for positron emission particle tracking through modification of solid surface chemistry
NASA Astrophysics Data System (ADS)
Fan, X.; Parker, D. J.; Smith, M. D.
The positron emission particle tracking (PEPT) technique has been widely used in science and engineering to obtain detailed information on particulate motion in granular materials and flow fields in multiphase systems. The technique involves tracking a single radioactively labelled particle by detecting the pairs of back-to-back 511 keV γ-rays arising from annihilation of emitted positrons. It is thus crucially dependent on the availability of suitably labelled tracer particles. With the present equipment, the optimum activity for a PEPT tracer is between 300 and 1000 μCi. The positron emitting radionuclide most often used is 18F in the form of fluoride ions. However, most materials have a very poor capacity to take up fluoride naturally. This paper presents a surface modification technique which was developed to improve the adsorption of 18F on solids and therefore extending the application of PEPT. For example, 200 μm MCC particles are the subject of many PEPT studies, but these particles only adsorb a few μCi 18F naturally, and cannot be used as tracers for PEPT. After surface modification, they take up about 700 μCi 18F, and can be tracked very well using PEPT.
Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer
Madani, Indira . E-mail: firstname.lastname@example.com; Duthoy, Wim; Derie, Cristina R.N.; De Gersem, Werner Ir.; Boterberg, Tom; Saerens, Micky; Jacobs, Filip Ir.; Gregoire, Vincent; Lonneux, Max; Vakaet, Luc; Vanderstraeten, Barbara; Bauters, Wouter; Bonte, Katrien; Thierens, Hubert; Neve, Wilfried de
Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.
Development of a prototype Open-close positron emission tomography system
NASA Astrophysics Data System (ADS)
Yamamoto, Seiichi; Okumura, Satoshi; Watabe, Tadashi; Ikeda, Hayato; Kanai, Yasukazu; Toshito, Toshiyuki; Komori, Masataka; Ogata, Yoshimune; Kato, Katsuhiko; Hatazawa, Jun
We developed a prototype positron emission tomography (PET) system based on a new concept called Open-close PET, which has two modes: open and close-modes. In the open-mode, the detector ring is separated into two halved rings and subject is imaged with the open space and projection image is formed. In the close-mode, the detector ring is closed to be a regular circular ring, and the subject can be imaged without an open space, and so reconstructed images can be made without artifacts. The block detector of the Open-close PET system consists of two scintillator blocks that use two types of gadolinium orthosilicate (GSO) scintillators with different decay times, angled optical fiber-based image guides, and a flat panel photomultiplier tube. The GSO pixel size was 1.6 × 2.4 × 7 mm and 8 mm for fast (35 ns) and slow (60 ns) GSOs, respectively. These GSOs were arranged into an 11 × 15 matrix and optically coupled in the depth direction to form a depth-of-interaction detector. The angled optical fiber-based image guides were used to arrange the two scintillator blocks at 22.5° so that they can be arranged in a hexadecagonal shape with eight block detectors to simplify the reconstruction algorithm. The detector ring was divided into two halves to realize the open-mode and set on a mechanical stand with which the distance between the two parts can be manually changed. The spatial resolution in the close-mode was 2.4-mm FWHM, and the sensitivity was 1.7% at the center of the field-of-view. In both the close- and open-modes, we made sagittal (y-z plane) projection images between the two halved detector rings. We obtained reconstructed and projection images of 18F-NaF rat studies and proton-irradiated phantom images. These results indicate that our developed Open-close PET is useful for some applications such as proton therapy as well as other applications such as molecular imaging.
The relationship between cerebrospinal fluid markers of Alzheimer pathology and positron emission tomography tau imaging.
Gordon, Brian A; Friedrichsen, Karl; Brier, Matthew; Blazey, Tyler; Su, Yi; Christensen, Jon; Aldea, Patricia; McConathy, Jonathan; Holtzman, David M; Cairns, Nigel J; Morris, John C; Fagan, Anne M; Ances, Beau M; Benzinger, Tammie L S
The two primary molecular pathologies in Alzheimer's disease are amyloid-β plaques and tau-immunoreactive neurofibrillary tangles. Investigations into these pathologies have been restricted to cerebrospinal fluid assays, and positron emission tomography tracers that can image amyloid-β plaques. Tau tracers have recently been introduced into the field, although the utility of the tracer and its relationship to other Alzheimer biomarkers are still unknown. Here we examined tau deposition in 41 cognitively normal and 11 cognitively impaired older adults using the radioactive tau ligand (18)F-AV-1451 (previously known as T807) who also underwent a lumbar puncture to assess cerebrospinal fluid levels of total tau (t-tau), phosphorylated tau181 (p-tau181) and amyloid-β42 Voxel-wise statistical analyses examined spatial patterns of tau deposition associated with cognitive impairment. We then related the amount of tau tracer uptake to levels of cerebrospinal fluid biomarkers. All analyses controlled for age and gender and, when appropriate, the time between imaging and lumbar puncture assessments. Symptomatic individuals (Clinical Dementia Rating > 0) demonstrated markedly increased levels of tau tracer uptake. This elevation was most prominent in the temporal lobe and temporoparietal junction, but extended more broadly into parietal and frontal cortices. In the entire cohort, there were significant relationships among all cerebrospinal fluid biomarkers and tracer uptake, notably for tau-related cerebrospinal fluid markers. After controlling for levels of amyloid-β42, the correlations with tau uptake were r = 0.490 (P < 0.001) for t-tau and r = 0.492 (P < 0.001) for p-tau181 Within the cognitively normal cohort, levels of amyloid-β42, but not t-tau or p-tau181, were associated with elevated tracer binding that was confined primarily to the medial temporal lobe and adjacent neocortical regions. AV-1451 tau binding in the medial temporal, parietal, and frontal cortices
Transfer of learning with an application to the physics of positron emission tomography
NASA Astrophysics Data System (ADS)
Aryal, Bijaya
A series of teaching activities using physical models was developed to present some portions of physics of Positron Emission Tomography (PET) and investigate students' understanding and transfer of learning in physics to a medical technology. A teaching interview protocol consistent with a qualitative research methodology was developed and administered to the students enrolled in an algebra-based introductory level physics course. 16 students participated in individual interviews and another 21 students participated in the group sessions. The major objectives of the teaching interviews were to investigate students' transfer of physics learning from their prior experiences to the provided physical models, from one model to the other and from the models to the PET problems. The study adapted phenomenological research methodology in analyzing students' use of cognitive resources and cognitive strategies during knowledge construction and reconstruction. A resource based transfer model framed under the cognitive theory of learning and consistent with contemporary views of transfer was used to describe the transfer of physics learning. Results of the study indicated both appropriate and inappropriate use of the students' prior conceptual resources in novel contexts. Scaffolding and questioning were found to be effective in activating appropriate and suppressing the inappropriate resources. The physical models used as analogies were found useful in transferring physics learning to understand image construction in PET. Positive transfer was possible when the models were introduced in an appropriate sequence. The results of the study indicate the occurrence of three types of non-scaffolded transfer---spontaneous, semi spontaneous and non-spontaneous. The research found connections between sequencing of hints and phrasing of information in activating students' different conceptual resources. A qualitative investigation based on Vygotsky's Zone of Proximal Development (ZPD
Development of Traceable Phantoms for Improved Image Quantification in Positron Emission Tomography
NASA Astrophysics Data System (ADS)
Zimmerman, Brian
Clinical trials for new drugs increasingly rely on imaging data to monitor patient response to the therapy being studied. In the case of radiopharmaceutical applications, imaging data are also used to estimate organ and tumor doses in order to arrive at the optimal dosage for safe and effective treatment. Positron Emission Tomography (PET) is one of the most commonly used imaging modalities for these types of applications. In large, multicenter trials it is crucial to minimize as much as possible the variability that arises due to use of different types of scanners and other instrumentation so that the biological response can be more readily evaluated. This can be achieved by ensuring that all the instruments are calibrated to a common standard and that their performance is continuously monitored throughout the trial. Maintaining links to a single standard also enables the comparability of data acquired on a heterogeneous collection of instruments in different clinical settings. As the standards laboratory for the United States, the National Institute of Standards and Technology (NIST) has been developing a suite of phantoms having traceable activity content to enable scanner calibration and performance testing. The configurations range from small solid cylindrical sources having volumes from 1 mL to 23 mL to large cylinders having a total volume of 9 L. The phantoms are constructed with 68Ge as a long-lived substitute for the more clinically useful radionuclide 18F. The contained activity values are traceable to the national standard for 68Ge and are also linked to the standard for 18F through a careful series of comparisons. The techniques that have been developed are being applied to a variety of new phantom configurations using different radionuclides. Image-based additive manufacturing techniques are also being investigated to create fillable phantoms having irregular shapes which can better mimic actual organs and tumors while still maintaining traceability
Development of a prototype Open-close positron emission tomography system.
Yamamoto, Seiichi; Okumura, Satoshi; Watabe, Tadashi; Ikeda, Hayato; Kanai, Yasukazu; Toshito, Toshiyuki; Komori, Masataka; Ogata, Yoshimune; Kato, Katsuhiko; Hatazawa, Jun
We developed a prototype positron emission tomography (PET) system based on a new concept called Open-close PET, which has two modes: open and close-modes. In the open-mode, the detector ring is separated into two halved rings and subject is imaged with the open space and projection image is formed. In the close-mode, the detector ring is closed to be a regular circular ring, and the subject can be imaged without an open space, and so reconstructed images can be made without artifacts. The block detector of the Open-close PET system consists of two scintillator blocks that use two types of gadolinium orthosilicate (GSO) scintillators with different decay times, angled optical fiber-based image guides, and a flat panel photomultiplier tube. The GSO pixel size was 1.6 × 2.4 × 7 mm and 8 mm for fast (35 ns) and slow (60 ns) GSOs, respectively. These GSOs were arranged into an 11 × 15 matrix and optically coupled in the depth direction to form a depth-of-interaction detector. The angled optical fiber-based image guides were used to arrange the two scintillator blocks at 22.5° so that they can be arranged in a hexadecagonal shape with eight block detectors to simplify the reconstruction algorithm. The detector ring was divided into two halves to realize the open-mode and set on a mechanical stand with which the distance between the two parts can be manually changed. The spatial resolution in the close-mode was 2.4-mm FWHM, and the sensitivity was 1.7% at the center of the field-of-view. In both the close- and open-modes, we made sagittal (y-z plane) projection images between the two halved detector rings. We obtained reconstructed and projection images of (18)F-NaF rat studies and proton-irradiated phantom images. These results indicate that our developed Open-close PET is useful for some applications such as proton therapy as well as other applications such as molecular imaging. PMID:26329212
Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging.
Xiao, Yuling; Hong, Hao; Javadi, Alireza; Engle, Jonathan W; Xu, Wenjin; Yang, Yunan; Zhang, Yin; Barnhart, Todd E; Cai, Weibo; Gong, Shaoqin
A multifunctional unimolecular micelle made of a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for cancer-targeted drug delivery and non-invasive positron emission tomography (PET) imaging in tumor-bearing mice. The hyperbranched amphiphilic block copolymer, Boltorn(®) H40-poly(L-glutamate-hydrazone-doxorubicin)-b-poly(ethylene glycol) (i.e., H40-P(LG-Hyd-DOX)-b-PEG), was conjugated with cyclo(Arg-Gly-Asp-D-Phe-Cys) peptides (cRGD, for integrin α(v)β(3) targeting) and macrocyclic chelators (1,4,7-triazacyclononane-N, N', N''-triacetic acid [NOTA], for (64)Cu-labeling and PET imaging) (i.e., H40-P(LG-Hyd-DOX)-b-PEG-OCH(3)/cRGD/NOTA, also referred to as H40-DOX-cRGD). The anti-cancer drug, doxorubicin (DOX) was covalently conjugated onto the hydrophobic segments of the amphiphilic block copolymer arms (i.e., PLG) via a pH-labile hydrazone linkage to enable pH-controlled drug release. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. cRGD-conjugated unimolecular micelles (i.e., H40-DOX-cRGD) exhibited a much higher cellular uptake in U87MG human glioblastoma cells due to integrin α(v)β(3)-mediated endocytosis than non-targeted unimolecular micelles (i.e., H40-DOX), thereby leading to a significantly higher cytotoxicity. In U87MG tumor-bearing mice, H40-DOX-cRGD-(64)Cu also exhibited a much higher level of tumor accumulation than H40-DOX-(64)Cu, measured by non-invasive PET imaging and confirmed by biodistribution studies and ex vivo fluorescence imaging. We believe that unimolecular micelles formed by hyperbranched amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics.
Development of a prototype Open-close positron emission tomography system
Yamamoto, Seiichi Okumura, Satoshi; Komori, Masataka; Ogata, Yoshimune; Kato, Katsuhiko; Watabe, Tadashi; Ikeda, Hayato; Kanai, Yasukazu; Toshito, Toshiyuki; Hatazawa, Jun
We developed a prototype positron emission tomography (PET) system based on a new concept called Open-close PET, which has two modes: open and close-modes. In the open-mode, the detector ring is separated into two halved rings and subject is imaged with the open space and projection image is formed. In the close-mode, the detector ring is closed to be a regular circular ring, and the subject can be imaged without an open space, and so reconstructed images can be made without artifacts. The block detector of the Open-close PET system consists of two scintillator blocks that use two types of gadolinium orthosilicate (GSO) scintillators with different decay times, angled optical fiber-based image guides, and a flat panel photomultiplier tube. The GSO pixel size was 1.6 × 2.4 × 7 mm and 8 mm for fast (35 ns) and slow (60 ns) GSOs, respectively. These GSOs were arranged into an 11 × 15 matrix and optically coupled in the depth direction to form a depth-of-interaction detector. The angled optical fiber-based image guides were used to arrange the two scintillator blocks at 22.5° so that they can be arranged in a hexadecagonal shape with eight block detectors to simplify the reconstruction algorithm. The detector ring was divided into two halves to realize the open-mode and set on a mechanical stand with which the distance between the two parts can be manually changed. The spatial resolution in the close-mode was 2.4-mm FWHM, and the sensitivity was 1.7% at the center of the field-of-view. In both the close- and open-modes, we made sagittal (y-z plane) projection images between the two halved detector rings. We obtained reconstructed and projection images of {sup 18}F-NaF rat studies and proton-irradiated phantom images. These results indicate that our developed Open-close PET is useful for some applications such as proton therapy as well as other applications such as molecular imaging.
Budget impact from the incorporation of positron emission tomography – computed tomography for staging lung cancers
Biz, Aline Navega; Caetano, Rosângela
OBJECTIVE To estimate the budget impact from the incorporation of positron emission tomography (PET) in mediastinal and distant staging of non-small cell lung cancer. METHODS The estimates were calculated by the epidemiological method for years 2014 to 2018. Nation-wide data were used about the incidence; data on distribution of the disease´s prevalence and on the technologies' accuracy were from the literature; data regarding involved costs were taken from a micro-costing study and from Brazilian Unified Health System (SUS) database. Two strategies for using PET were analyzed: the offer to all newly-diagnosed patients, and the restricted offer to the ones who had negative results in previous computed tomography (CT) exams. Univariate and extreme scenarios sensitivity analyses were conducted to evaluate the influence from sources of uncertainties in the parameters used. RESULTS The incorporation of PET-CT in SUS would imply the need for additional resources of 158.1 BRL (98.2 USD) million for the restricted offer and 202.7 BRL (125.9 USD) million for the inclusive offer in five years, with a difference of 44.6 BRL (27.7 USD) million between the two offer strategies within that period. In absolute terms, the total budget impact from its incorporation in SUS, in five years, would be 555 BRL (345 USD) and 600 BRL (372.8 USD) million, respectively. The costs from the PET-CT procedure were the most influential parameter in the results. In the most optimistic scenario, the additional budget impact would be reduced to 86.9 BRL (54 USD) and 103.8 BRL (64.5 USD) million, considering PET-CT for negative CT and PET-CT for all, respectively. CONCLUSIONS The incorporation of PET in the clinical staging of non-small cell lung cancer seems to be financially feasible considering the high budget of the Brazilian Ministry of Health. The potential reduction in the number of unnecessary surgeries may cause the available resources to be more efficiently allocated. PMID:26274871
Fluorodeoxyglucose Positron Emission Tomography Response and Normal Tissue Regeneration After Stereotactic Body Radiotherapy to Liver Metastases
Stinauer, Michelle A.; Diot, Quentin; Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.
Purpose: To characterize changes in standardized uptake value (SUV) in positron emission tomography (PET) scans and determine the pace of normal tissue regeneration after stereotactic body radiation therapy (SBRT) for solid tumor liver metastases. Methods and Materials: We reviewed records of patients with liver metastases treated with SBRT to {>=}40 Gy in 3-5 fractions. Evaluable patients had pretreatment PET and {>=}1 post-treatment PET. Each PET/CT scan was fused to the planning computed tomography (CT) scan. The maximum SUV (SUV{sub max}) for each lesion and the total liver volume were measured on each PET/CT scan. Maximum SUV levels before and after SBRT were recorded. Results: Twenty-seven patients with 35 treated liver lesions were studied. The median follow-up was 15.7 months (range, 1.5-38.4 mo), with 5 PET scans per patient (range, 2-14). Exponential decay curve fitting (r=0.97) showed that SUV{sub max} declined to a plateau of 3.1 for controlled lesions at 5 months after SBRT. The estimated SUV{sub max} decay half-time was 2.0 months. The SUV{sub max} in controlled lesions fluctuated up to 4.2 during follow-up and later declined; this level is close to 2 standard deviations above the mean normal liver SUV{sub max} (4.01). A failure cutoff of SUV{sub max} {>=}6 is twice the calculated plateau SUV{sub max} of controlled lesions. Parenchymal liver volume decreased by 20% at 3-6 months and regenerated to a new baseline level approximately 10% below the pretreatment level at 12 months. Conclusions: Maximum SUV decreases over the first months after SBRT to plateau at 3.1, similar to the median SUV{sub max} of normal livers. Transient moderate increases in SUV{sub max} may be observed after SBRT. We propose a cutoff SUV{sub max} {>=}6, twice the baseline normal liver SUV{sub max}, to score local failure by PET criteria. Post-SBRT values between 4 and 6 would be suspicious for local tumor persistence or recurrence. The volume of normal liver reached nadir 3
Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor
NASA Astrophysics Data System (ADS)
Qin, Zhengtao
Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and
[Examination of myocardial perfusion with positron emission tomography: a clinically useful and valid method?].
vom Dahl, J
Positron emission tomography (PET) of the heart has gained widespread scientific and clinical acceptance with regard to 2 indications: 1. the detection of perfusion abnormalities by qualitative and semiquantitative analyses of perfusion images at rest and during physical or pharmacological stress using well validated perfusion tracers such as N-13 ammonia, Rb-82 rubidiumchloride, or O-15 labeled water, 2. Viability imaging of myocardial regions with reduced contractility by combining perfusion measurements with substrate metabolism as assessed from F-18 deoxyglucose utilization. This overview summarizes the use of PET as a perfusion imaging method. With a sensitivity > 90% in combination with a high specificity, PET is today the best available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. The high diagnostic accuracy and the methological advantages as compared to conventional scintigraphy allows to use PET perfusion imaging for detection of subtle changes of the perfusion reserve for detection of CAD in high risk but asymptomatic patients as well as in patients with proven CAD undergoing various treatment forms such as risk factor reduction or coronary revascularization. In patients following orthotopic heart transplantation, evolving transplant vasculopathy can be detected at an early stage. Quantitative PET imaging at rest allows for detection of myocardial viability since cellular survival is based on maintenance of a minimal perfusion and structural changes correlate to the degree of perfusion reduction. Furthermore, quantitative assessment of the myocardial perfusion reserve detects the magnitude and competence of collaterals in regions with occluded epicardial arteries and thus, imaging of several coronary distribution territories in one noninvasive study. The cost of
Image reconstruction for a Positron Emission Tomograph optimized for breast cancer imaging
Virador, Patrick R.G.
The author performs image reconstruction for a novel Positron Emission Tomography camera that is optimized for breast cancer imaging. This work addresses for the first time, the problem of fully-3D, tomographic reconstruction using a septa-less, stationary, (i.e. no rotation or linear motion), and rectangular camera whose Field of View (FOV) encompasses the entire volume enclosed by detector modules capable of measuring Depth of Interaction (DOI) information. The camera is rectangular in shape in order to accommodate breasts of varying sizes while allowing for soft compression of the breast during the scan. This non-standard geometry of the camera exacerbates two problems: (a) radial elongation due to crystal penetration and (b) reconstructing images from irregularly sampled data. Packing considerations also give rise to regions in projection space that are not sampled which lead to missing information. The author presents new Fourier Methods based image reconstruction algorithms that incorporate DOI information and accommodate the irregular sampling of the camera in a consistent manner by defining lines of responses (LORs) between the measured interaction points instead of rebinning the events into predefined crystal face LORs which is the only other method to handle DOI information proposed thus far. The new procedures maximize the use of the increased sampling provided by the DOI while minimizing interpolation in the data. The new algorithms use fixed-width evenly spaced radial bins in order to take advantage of the speed of the Fast Fourier Transform (FFT), which necessitates the use of irregular angular sampling in order to minimize the number of unnormalizable Zero-Efficiency Bins (ZEBs). In order to address the persisting ZEBs and the issue of missing information originating from packing considerations, the algorithms (a) perform nearest neighbor smoothing in 2D in the radial bins (b) employ a semi-iterative procedure in order to estimate the unsampled data
The Silicon Photomultiplier for application to high-resolution Positron Emission Tomography
NASA Astrophysics Data System (ADS)
Herbert, D. J.; Moehrs, S.; D'Ascenzo, N.; Belcari, N.; Del Guerra, A.; Morsani, F.; Saveliev, V.
Positron Emission Tomography (PET) for small animal studies requires high-resolution gamma cameras with high sensitivity. Traditionally, inorganic scintillators are used and, in recent times, coupled to position sensitive PMTs to achieve a higher resolution. Such PSPMTs are costly, operated at high voltage and have a relatively low packing fraction. However, their advantage, compared to current solid state photodetectors, is their high signal-to-noise ratio. The Silicon Photomultiplier (SiPM) is a silicon diode detector that shows great promise as a photodetector for scintillators and hence application in nuclear medicine imaging applications. The microcell MRS (Metal-Resistor-Semiconductor) structure of the SiPM leads to a self-quenching, Geiger-mode avalanche photodiode (GAPD), that produces a large gain (5×105) at low bias voltage (50 V) and proportional output for moderate photon flux. Such a compact silicon detector, with a performance similar to a PMT, is obviously well disposed to being developed into a close-packed array in order to have a position-sensitive detection surface. We propose a miniature, high-resolution camera for a small-animal PET imaging system that is based on such an array of SiPM. The design is based upon the classic Anger camera principle; each detector module consists of a continuous slab of scintillator, viewed by a matrix of SiPM. A detector head of 4×4 cm2 in area is proposed, constructed from three such modules of the continuous camera described above. The stacked layers would give the system intrinsic depth of interaction (DOI) information. A summary of measured SiPM performance and results of a simulation of the proposed camera, using the Monte Carlo package GEANT4, are presented. It is shown that using three layers of 5 mm thick LSO, gives an efficiency of 68% with maximum count rates in the front layers. Intrinsic spatial resolution of <0.4 mm FWHM was found although this is degraded at the edges. Although the inclusion of DOI
A Gaussian mixture model for definition of lung tumor volumes in positron emission tomography
Aristophanous, Michalis; Penney, Bill C.; Martel, Mary K.; Pelizzari, Charles A.
The increased interest in {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in radiation treatment planning in the past five years necessitated the independent and accurate segmentation of gross tumor volume (GTV) from FDG-PET scans. In some studies the radiation oncologist contours the GTV based on a computed tomography scan, while incorporating pertinent data from the PET images. Alternatively, a simple threshold, typically 40% of the maximum intensity, has been employed to differentiate tumor from normal tissue, while other researchers have developed algorithms to aid the PET based GTV definition. None of these methods, however, results in reliable PET tumor segmentation that can be used for more sophisticated treatment plans. For this reason, we developed a Gaussian mixture model (GMM) based segmentation technique on selected PET tumor regions from non-small cell lung cancer patients. The purpose of this study was to investigate the feasibility of using a GMM-based tumor volume definition in a robust, reliable and reproducible way. A GMM relies on the idea that any distribution, in our case a distribution of image intensities, can be expressed as a mixture of Gaussian densities representing different classes. According to our implementation, each class belongs to one of three regions in the image; the background (B), the uncertain (U) and the target (T), and from these regions we can obtain the tumor volume. User interaction in the implementation is required, but is limited to the initialization of the model parameters and the selection of an 'analysis region' to which the modeling is restricted. The segmentation was developed on three and tested on another four clinical cases to ensure robustness against differences observed in the clinic. It also compared favorably with thresholding at 40% of the maximum intensity and a threshold determination function based on tumor to background image intensities proposed in a recent paper. The parts of
Multimodality imaging probe for positron emission tomography and fluorescence imaging studies.
Pandey, Suresh K; Kaur, Jasmeet; Easwaramoorthy, Balu; Shah, Ankur; Coleman, Robert; Mukherjee, Jogeshwar
Our goal is to develop multimodality imaging agents for use in cell tracking studies by positron emission tomography (PET) and optical imaging (OI). For this purpose, bovine serum albumin (BSA) was complexed with biotin (histologic studies), 5(6)-carboxyfluorescein, succinimidyl ester (FAM SE) (OI studies), and diethylenetriamine pentaacetic acid (DTPA) for chelating gallium 68 (PET studies). For synthesis of BSA-biotin-FAM-DTPA, BSA was coupled to (+)-biotin N-hydroxysuccinimide ester (biotin-NHSI). BSA-biotin was treated with DTPA-anhydride and biotin-BSA-DTPA was reacted with FAM. The biotin-BSA-DTPA-FAM was reacted with gallium chloride 3 to 5 mCi eluted from the generator using 0.1 N HCl and was passed through basic resin (AG 11 A8) and 150 μCi (100 μL, pH 7-8) was incubated with 0.1 mg of FAM conjugate (100 μL) at room temperature for 15 minutes to give 68Ga-BSA-biotin-DTPA-FAM. A shaved C57 black mouse was injected with FAM conjugate (50 μL) at one flank and FAM-68Ga (50 μL, 30 μCi) at the other. Immediately after injection, the mouse was placed in a fluorescence imaging system (Kodak In-Vivo F, Bruker Biospin Co., Woodbridge, CT) and imaged (λex: 465 nm, λem: 535 nm, time: 8 seconds, Xenon Light Source, Kodak). The same mouse was then placed under an Inveon microPET scanner (Siemens Medical Solutions, Knoxville, TN) injected (intravenously) with 25 μCi of 18F and after a half-hour (to allow sufficient bone uptake) was imaged for 30 minutes. Molecular weight determined using matrix-associated laser desorption ionization (MALDI) for the BSA sample was 66,485 Da and for biotin-BSA was 67,116 Da, indicating two biotin moieties per BSA molecule; for biotin-BSA-DTPA was 81,584 Da, indicating an average of 30 DTPA moieties per BSA molecule; and for FAM conjugate was 82,383 Da, indicating an average of 1.7 fluorescent moieties per BSA molecule. Fluorescence imaging clearly showed localization of FAM conjugate and FAM-68Ga at respective flanks of the mouse
Modeling clustered activity increase in amyloid-beta positron emission tomographic images with statistical descriptors
Shokouhi, Sepideh; Rogers, Baxter P; Kang, Hakmook; Ding, Zhaohua; Claassen, Daniel O; Mckay, John W; Riddle, William R
Background Amyloid-beta (Aβ) imaging with positron emission tomography (PET) holds promise for detecting the presence of Aβ plaques in the cortical gray matter. Many image analyses focus on regional average measurements of tracer activity distribution; however, considerable additional information is available in the images. Metrics that describe the statistical properties of images, such as the two-point correlation function (S2), have found wide applications in astronomy and materials science. S2 provides a detailed characterization of spatial patterns in images typically referred to as clustering or flocculence. The objective of this study was to translate the two-point correlation method into Aβ-PET of the human brain using 11C-Pittsburgh compound B (11C-PiB) to characterize longitudinal changes in the tracer distribution that may reflect changes in Aβ plaque accumulation. Methods We modified the conventional S2 metric, which is primarily used for binary images and formulated a weighted two-point correlation function (wS2) to describe nonbinary, real-valued PET images with a single statistical function. Using serial 11C-PiB scans, we calculated wS2 functions from two-dimensional PET images of different cortical regions as well as three-dimensional data from the whole brain. The area under the wS2 functions was calculated and compared with the mean/median of the standardized uptake value ratio (SUVR). For three-dimensional data, we compared the area under the wS2 curves with the subjects' cerebrospinal fluid measures. Results Overall, the longitudinal changes in wS2 correlated with the increase in mean SUVR but showed lower variance. The whole brain results showed a higher inverse correlation between the cerebrospinal Aβ and wS2 than between the cerebrospinal Aβ and SUVR mean/median. We did not observe any confounding of wS2 by region size or injected dose. Conclusion The wS2 detects subtle changes and provides additional information about the binding
Spatiotemporal Stability of Cu-ATSM and FLT Positron Emission Tomography Distributions During Radiation Therapy
Bradshaw, Tyler J.; Yip, Stephen; Jallow, Ngoneh; Forrest, Lisa J.; Jeraj, Robert
Purpose: In dose painting, in which functional imaging is used to define biological targets for radiation therapy dose escalation, changes in spatial distributions of biological properties during treatment can compromise the quality of therapy. The goal of this study was to assess the spatiotemporal stability of 2 potential dose painting targets—hypoxia and proliferation—in canine tumors during radiation therapy. Methods and Materials: Twenty-two canine patients with sinonasal tumors (14 carcinoma and 8 sarcoma) were imaged before hypofractionated radiation therapy with copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) positron emission tomography/computed tomography (PET/CT) for hypoxia and 3′-deoxy-3′-{sup 18}F-fluorothymidine (FLT) PET/CT for proliferation. The FLT scans were repeated after 2 fractions and the Cu-ATSM scans after 3 fractions. Midtreatment PET/CT images were deformably registered to pretreatment PET/CT images. Voxel-based Spearman correlation coefficients quantified the spatial stability of Cu-ATSM and FLT uptake distributions between pretreatment and midtreatment scans. Paired t tests determined significant differences between the patients' respective Cu-ATSM and FLT correlations coefficients. Standardized uptake value measures were also compared between pretreatment and midtreatment scans by use of paired t tests. Results: Spatial distributions of Cu-ATSM and FLT uptake were stable through midtreatment for both sarcomas and carcinomas: the population mean ± standard deviation in Spearman correlation coefficient was 0.88 ± 0.07 for Cu-ATSM and 0.79 ± 0.13 for FLT. The patients' Cu-ATSM correlation coefficients were significantly higher than their respective FLT correlation coefficients (P=.001). Changes in Cu-ATSM SUV measures from pretreatment to midtreatment were histology dependent: carcinomas experienced significant decreases in Cu-ATSM uptake (P<.05), whereas sarcomas did not (P>.20). Both histologies
Role of Positron Emission Tomography-Computed Tomography in the Management of Anal Cancer
Mistrangelo, Massimiliano; Pelosi, Ettore; Bello, Marilena; Ricardi, Umberto; Milanesi, Enrica; Cassoni, Paola; Baccega, Massimo; Filippini, Claudia; Racca, Patrizia; Lesca, Adriana; Munoz, Fernando H.; Fora, Gianluca; Skanjeti, Andrea; Cravero, Francesca; Morino, Mario
Purpose: Pre- and post-treatment staging of anal cancer are often inaccurate. The role of positron emission tomograpy-computed tomography (PET-CT) in anal cancer is yet to be defined. The aim of the study was to compare PET-CT with CT scan, sentinel node biopsy results of inguinal lymph nodes, and anal biopsy results in staging and in follow-up of anal cancer. Methods and Materials: Fifty-three consecutive patients diagnosed with anal cancer underwent PET-CT. Results were compared with computed tomography (CT), performed in 40 patients, and with sentinel node biopsy (SNB) (41 patients) at pretreatment workup. Early follow-up consisted of a digital rectal examination, an anoscopy, a PET-CT scan, and anal biopsies performed at 1 and 3 months after the end of treatment. Data sets were then compared. Results: At pretreatment assessment, anal cancer was identified by PET-CT in 47 patients (88.7%) and by CT in 30 patients (75%). The detection rates rose to 97.9% with PET-CT and to 82.9% with CT (P=.042) when the 5 patients who had undergone surgery prior to this assessment and whose margins were positive at histological examination were censored. Perirectal and/or pelvic nodes were considered metastatic by PET-CT in 14 of 53 patients (26.4%) and by CT in 7 of 40 patients (17.5%). SNB was superior to both PET-CT and CT in detecting inguinal lymph nodes. PET-CT upstaged 37.5% of patients and downstaged 25% of patients. Radiation fields were changed in 12.6% of patients. PET-CT at 3 months was more accurate than PET-CT at 1 month in evaluating outcomes after chemoradiation therapy treatment: sensitivity was 100% vs 66.6%, and specificity was 97.4% vs 92.5%, respectively. Median follow-up was 20.3 months. Conclusions: In this series, PET-CT detected the primary tumor more often than CT. Staging of perirectal/pelvic or inguinal lymph nodes was better with PET-CT. SNB was more accurate in staging inguinal lymph nodes.
Design and development of a dedicated mammary and axillary region positron emission tomography system
NASA Astrophysics Data System (ADS)
Doshi, Niraj Kumar
Breast cancer is the second leading cause of cancer death in women. Currently, mammography and physical breast examination, both non-invasive techniques, provide the two most effective methods available for screening potential breast cancer patients. During the management of patients, however, several invasive techniques such as axillary lymph node dissection, core biopsies and lumpectomies, are utilized to determine the stage or malignancy of the disease with significant cost and morbidity associated with them. Positron Emission Tomography (PET), using [F-18] fluorodeoxyglucose (FDG) tracer is a sensitive and non-invasive imaging modality that may be a cost-effective alternative to certain invasive procedures. In this project we have developed a low cost, high performance, dedicated PET camera (maxPET) for mammary and axillary region imaging. The system consists of two 15x15 cm2 planar scintillation detector arrays composed of modular detectors operating in coincidence. The modular detectors are comprised of a 9x9 array of 3x3x20 mm3 lutetiurn oxyorthosilicate (LSO) detector elements, read out by a 5x5 array of position- sensitive photomultiplier tubes. The average measured intrinsic spatial resolution of a detector module is 2.26 mm with a sensitivity of up to 40% for a central point source. The measured coincidence timing resolution for two modules is 2.4 ns. The average energy resolution measured across the entire two detector plates is 21.6%. The coincidence timing resolution for the entire system is 8.1 ns. A line bar phantom was imaged and images were reconstructed using the focal plane tomography algorithm. A 4 mm projection image resolution was measured based on profiles taken through the line bar phantom images. The goal of the maxPET system will be to aid in breast cancer patient management by assisting in imaging women with dense, fibro-glandular breasts, detecting axillary lymph node metastases without surgery, monitoring chemotherapy effectiveness and
Ventilation/Perfusion Positron Emission Tomography—Based Assessment of Radiation Injury to Lung
Siva, Shankar; Hardcastle, Nicholas; Kron, Tomas; Bressel, Mathias; Callahan, Jason; MacManus, Michael P.; Shaw, Mark; Plumridge, Nikki; Hicks, Rodney J.; Steinfort, Daniel; Ball, David L.; Hofman, Michael S.
Purpose: To investigate {sup 68}Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). Methods and Materials: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). Results: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r{sup 2}=0.99, P<.01), with ventilation strongly negatively linear (r{sup 2}=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. Conclusions: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET
Preliminary safety evaluation of a cyclotron facility for positron emission tomography imaging.
González, L; Vañó, E; Cordeiro, C A; Carreras, J L
This work describes the design characteristics of a medical imaging centre which uses positron emission tomography, with a cyclotron for fluorine-18 and nitrogen-13 production, and which has provided experimental information on operational data recorded by area dosimetry since 1995. Doses to radiopharmacy and medical staff have been measured both in normal work and in some handling incidents. Data on radiation levels in the installation have also been obtained and related to design details and shielding. Area dosimetry was carried out using a five-stationary detector network, with a sampling rate of 2 min(-1), and by thermoluminescent dosimetry (TLD). Staff were also monitored by TLD, using extra chips for finger dosimetry and to duplicate individual whole-body dosimetry in order to measure doses in certain single operations. For normal work, average whole-body doses to radiopharmacy staff were between 0.03 and 0.28 mSv/month, wrist doses were between 0.42 and 2.67 mSv/month, and finger doses were between 1.4 and 7.7 mSv/day for the left hand and 0.8 and 2.4 mSv/day for the right hand; such variation reflects the differing expertise of staff and the role played by optimisation. Finger doses between 16 and 131 mSv were measured in handling incidents, and finger doses of 20.2 and 20.7 mSv for the left hand and 22.0 and 22.3 mSv for the right hand were measured during handling of a syringe without shielding, containing 3 GBq. For medical staff, contributions to the whole-body dose of 2.0 and 1.9 microSv/procedure were measured for injection and placing the patient on the examination couch, respectively. Dose measurement on the middle finger of the right hand gives an average of 70 microSv during the injection. The provisions regarding the shielding design have proved to be adequate and effective during a 3-year operational period. Operational doses to medical staff are comparatively low, while radiopharmacy staff are the most exposed. The finger doses in these
Label-free assay for the assessment of nonspecific binding of positron emission tomography tracer candidates.
Assmus, Frauke; Seelig, Anna; Gobbi, Luca; Borroni, Edilio; Glaentzlin, Patricia; Fischer, Holger
Positron emission tomography (PET) is a valuable non-invasive technique for the visualization of drug tissue distribution and receptor occupancy at the target site in living animals and men. Many potential PET tracers, however, fail due to an unfavorably high non-specific binding (NSB) to non-target proteins and phospholipid membranes which compromises the sensitivity of PET. Hence, there is a high demand to assess the extent of NSB as early as possible in the PET tracer development process, preferentially before ligands are radiolabeled and elaborate imaging studies are performed. The purpose of this study was to establish a novel Lipid Membrane Binding Assay (LIMBA) for assessing the tendency of potential tracers to bind non-specifically to brain tissue. The assay works with unlabeled compounds and allows the medium-throughput measurement of brain tissue/water distribution coefficients, logDbrain (pH7.4), at minimal expense of animal tissue. To validate LIMBA, logDbrain (pH7.4) values were measured and compared with NSB estimates derived from in vivo PET studies in human brain (n=10 tracers, literature data), and in vitro autoradiography studies in rat and mouse brain slices (n=30 tritiated radioligands). Good agreement between logDbrain (pH7.4) and the volume of distribution in brain of non-specifically bound tracer in PET was achieved, pertaining to compounds classified as non-substrates of P-glycoprotein (R(2)≥0.88). The ability of LIMBA for the prediction of NSB was further supported by the strong correlation between logDbrain (pH7.4) and NSB in brain autoradiography (R(2)≥0.76), whereas octanol/water distribution coefficients, logDoct (pH7.4) were less predictive. In conclusion, LIMBA provides a fast and reliable tool for identifying compounds with unfavorably high NSB in brain tissue. The data may be used in conjunction with other parameters like target affinity, density and membrane permeability for the selection of most promising compounds to be
Spectrum of fluorodeoxyglucose-positron emission tomography/computed tomography and magnetic resonance imaging findings of ovarian tumors.
Kitajima, Kazuhiro; Ueno, Yoshiko; Maeda, Tetsuo; Murakami, Koji; Kaji, Yasushi; Kita, Masato; Suzuki, Kayo; Sugimura, Kazuro
The purpose of this article is to review fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI) findings in a variety of benign, malignant, and borderline malignant ovarian tumors. It is advantageous to become familiar with the wide variety of FDG-PET/CT findings of this entity. Benign ovarian tumors generally have faint uptake, whereas endometriomas, fibromas, and teratomas show mild to moderate uptake. Malignant ovarian tumors generally have intense uptake, whereas tumors with a small solid component often show minimal uptake.
Melorheostosis associated with peripheral form spondyloarthropathy: new image with 18-fluoride positron emission tomoscintigraphy coupled to computed tomography
Hassani, Hakim; Slama, Jérôme; Hayem, Gilles; Ben Ali, Khadija; Sarda-Mantel, Laure; Burg, Samuel; Le Guludec, Dominique
Melorheostosis is a rare benign bone pathology which can be responsible for incapacitating pain and bone deformations. Its imaging abnormalities are often typical. We describe here the case of a patient with melorheostosis involving the lower limbs, associated with a peripheral form of inflammatory spondyloarthropathy, who underwent 18FNa positron emission tomography coupled to a computed tomography scan. Our objective is to present this new image, to show the value of this new modality and emphasize its advantages compared to the 99mTechnetium bone scan.
Metastatic superscan in prostate carcinoma on gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography scan
Agarwal, Krishan Kant; Tripathi, Madhavi; Kumar, Rajeev; Bal, Chandrasekhar
We describe the imaging features of a metastatic superscan on gallium-68 Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)], abbreviated as gallium-68-prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) imaging. 68Ga-PSMA is novel radiotracer undergoing evaluation for PET/CT imaging of prostate carcinoma. This patient had a superscan of metastases on conventional bone scintigraphy and was referred for 68Ga-PSMA PET/CT to evaluate the feasibility of 177Lu-PSMA therapy. PMID:27095868
[Capabilities of positron emission tomography to study mecha-nisms of multiple sclerosis: own data and literature].
Stolyarov, I D; Petrov, A M; Shkil'nyuk, G G; Kataeva, G V; Prakhova, L N
The article presents the literature data and results of our own researchon the use of positron emission tomography (PET) with different radiotracersin multiple sclerosis (MS). Informationon the operating principles of PET and PET studies with different radiotracers are considered. The results of PET studiesin different typesof MS, including determinationof the localization of neuronal damagein the corticalgray matter, assessmentof microglial activation, study of the relationship between glucose metabolismin the brain and the severity of cognitive impairmentin MS, can providenew information about the pathogenesis ofMS.
Multiple pulmonary sclerosing hemangiomas (pneumocytoma) mimicking lung metastasis detected in fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography
Kamaleshwaran, Koramadai Karuppusamy; Rajan, Firoz; Mehta, Sangita; Mohanan, Vyshakh; Shinto, Ajit Sugunan
Pulmonary sclerosing hemangioma (PSH), or the alternative name of "sclerosing pneumocytoma," is a rare benign neoplasm. PSH is often asymptomatic and presents as a solitary or multiple pulmonary nodules on radiologic imaging studies. Few articles have been reported to describe the fluorodeoxyglucose positron emission tomography (FDG PET) findings about PSH. The authors describe an interesting but uncommonly encountered cause of false positive FDG PET scan in the thorax in a 25-year-old woman, a known case of arteriovenous malformation of oral cavity who underwent embolization and presented with incidental detection of bilateral lung nodules. She is asymptomatic and is on follow-up. PMID:25210285
Multiple pulmonary sclerosing hemangiomas (pneumocytoma) mimicking lung metastasis detected in fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography.
Kamaleshwaran, Koramadai Karuppusamy; Rajan, Firoz; Mehta, Sangita; Mohanan, Vyshakh; Shinto, Ajit Sugunan
Pulmonary sclerosing hemangioma (PSH), or the alternative name of "sclerosing pneumocytoma," is a rare benign neoplasm. PSH is often asymptomatic and presents as a solitary or multiple pulmonary nodules on radiologic imaging studies. Few articles have been reported to describe the fluorodeoxyglucose positron emission tomography (FDG PET) findings about PSH. The authors describe an interesting but uncommonly encountered cause of false positive FDG PET scan in the thorax in a 25-year-old woman, a known case of arteriovenous malformation of oral cavity who underwent embolization and presented with incidental detection of bilateral lung nodules. She is asymptomatic and is on follow-up.
Positron emission tomography assessment of effects of benzodiazepines on regional glucose metabolic rate in patients with anxiety disorder
Buchsbaum, M.S.; Wu, J.; Haier, R.; Hazlett, E.; Ball, R.; Katz, M.; Sokolski, K.; Lagunas-Solar, M.; Langer, D.
Patients with generalized anxiety disorder (n = 18) entered a 21-day, double-blind, placebo-controlled random assignment trial of clorazepate. Positron emission tomography with YF-deoxyglucose was carried out before and after treatment. Decreases in glucose metabolic rate in visual cortex and relative increases in the basal ganglia and thalamus were found. A correlation between regional changes in metabolic rate and regional benzodiazepine receptor binding density from other human autopsy studies was observed; brain regions highest in receptor density showed the greatest decrease in rate.
Clinical usefulness of post-operative 18F-fluorodeoxyglucose positron emission tomography-computed tomography in canine hemangiosarcoma
Lee, Gahyun; Kwon, Seong Young; Son, Kyuyeol; Park, Seungjo; Lee, Ju-hwan; Cho, Kyoung-Oh; Min, Jung-Joon
This report describes the usefulness of positron emission tomography-computed tomography (PET-CT) for evaluating recurrent or residual tumors following surgery. CT and 18F-fluorodeoxyglucose PET-CT were pre- and post-operatively applied to multiple masses in a dog with hemangiosarcoma. The distinction between the left subcutaneous mass and the peritoneum was clarified on pre-operative CT examination, and malignancy was suspected based on PET-CT. A recurrent or residual tumor in the left subcutaneous region was suspected on post-operative PET-CT, and confirmed through histopathologic examination. PMID:26645332
Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study
Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.
Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for /sup 82/Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.
Positron Emission Mammography Imaging with Low Activity Fluorodeoxyglucose and Novel Utilization in Core-needle Biopsy Sampling
Choudhery, Sadia; Seiler, Stephen
Positron emission mammography (PEM), a relatively novel breast imaging modality, provides certain advantages over magnetic resonance imaging, including the ability to image biopsy samples. However, the radiation activity associated with PEM has remained a concern in clinical practice. We present a case of an invasive ductal carcinoma that was adequately imaged with a much lower than the standard 185 to 370 MBq activity of 18F-fluorodeoxyglucose. In addition, we demonstrate ultrasound-guided core-needle biopsy sample imaging with PEM to assess adequacy of sampling, a strategy that has previously only been documented with vacuum-assisted biopsy samples. PMID:25709550
New techniques for positron emission tomography in the study of human neurological disorders
Kuhl, D.E.
This progress report describes accomplishments of four programs. The four programs are entitled (1) Faster,simpler processing of positron-computing precursors: New physicochemical approaches, (2) Novel solid phase reagents and methods to improve radiosynthesis and isotope production, (3) Quantitative evaluation of the extraction of information from PET images, and (4) Optimization of tracer kinetic methods for radioligand studies in PET.
SU-E-T-230: Measurement of Proton-Activated Positron Emission with PRESAGE 3-D Dosimeters
Carroll, M; Mawlawi, O; Ibbott, G; Adamovics, J
Purpose: Measurement of positron emission following proton beam irradiation of a target has been studied as a method of in-vivo dosimetry. Relative dosimetry studies between a phantom and treatment plan are susceptible to range uncertainties from material heterogeneities and setup error. By using the radiochromic polyurethane dosimeter PRESAGE, we can correlate the proton dose distribution to the PET activity measurement within a single detector. The PRESAGE formulation used was developed for high-LET proton radiotherapy, has similar density and RLSP to tissue, and consists of a greater carbon component, which gives it a higher positron signal than many other 3D detectors. Methods: Three cylindrical PRESAGE dosimeters were irradiated semi-uniformly to 500 cGy with 180- MeV protons. The beam was directed along the dosimeter axis and delivered a 2-cm SOBP at the center of the dosimeter. The dosimeters were rushed to a nearby PET/CT where imaging began within 15 minutes, less than a single half-life of 11C. A 3-hr measurement captured the full activation decay. Afterwards, the dose profiles were measured by optical-CT. A direct comparison between the measured dose and the positron emission was performed using CERR software. Results: The correlations between dose distributions and PET activity were consistent with previous studies in that the proximal region of the SOBP displayed the highest activity. The spatial distributions between the dose and activity were similar. Along the central axis of the beam, we found a shift in the distal 80% of 1 cm. The lateral profile showed good agreement between dose and activity. PET imaging times between 30-min and 3-hrs showed <5% discrepancy. Conclusion: PRESAGE dosimeters offer a strong and unique potential to accurately correlate dosimetric and PET activation information. Implementation in an anthropomorphic phantom could be used to study representative treatment plans. NIH grant 5R01CA100835.
Identification of ischemic and hibernating myocardium: feasibility of post-exercise F-18 deoxyglucose positron emission tomography
Marwick, T.H.; MacIntyre, W.J.; Salcedo, E.E.; Go, R.T.; Saha, G.; Beachler, A. )
The identification of ischemic and hibernating myocardium facilitates the selection of patients most likely to benefit from revascularization. This study examined the feasibility of metabolic imaging, using post-exercise F-18 deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of both ischemia and hibernation in 27 patients with known coronary anatomy. Normal post-exercise FDG uptake was defined in each patient by reference to normal resting perfusion and normal coronary supply. Abnormal elevation of FDG (ischemia or hibernation) was compared in 13 myocardial segments in each patient, with the results of dipyridamole stress perfusion imaging performed by rubidium-82 positron emission tomography (Rb-PET). Myocardial ischemia was diagnosed by either FDG-PET or Rb-PET in 34 segments subtended by significant local coronary stenoses. Increased FDG uptake was present in 32/34 (94%) and a reversible perfusion defect was identified by Rb-PET in 22/34 (65%, p less than .01). In 3 patients, ischemia was identified by metabolic imaging alone. In 16 patients with previous myocardial infarction, perfusion defects were present at rest in 89 regions, 30 of which (34%) demonstrated increased FDG uptake, consistent with the presence of hibernation. Increased post-exercise FDG uptake appears to be a sensitive indicator of ischemia and myocardial hibernation. Increased post-exercise FDG uptake, appears to be a sensitive indicator of ischemia and myocardial hibernation. This test may be useful in selecting post-infarction patients for revascularization.
F-18 deoxyglucose and stress N-13 ammonia positron emission tomography in anterior wall healed myocardial infarction
Fudo, T.; Kambara, H.; Hashimoto, T.; Hayashi, M.; Nohara, R.; Tamaki, N.; Yonekura, Y.; Senda, M.; Konishi, J.; Kawai, C.
To evaluate myocardial blood flow and glucose utilization, N-13 ammonia (NH3) and F-18 deoxyglucose positron emission tomography scanning was performed in 22 patients with previous anterior wall myocardial infarction, using a high-resolution, multi-slice, whole-body scanner. The N-13 ammonia study was performed at rest and after exercise. The F-18 deoxyglucose study was performed at rest after fasting greater than 5 hours. The N-13 ammonia study revealed a hypoperfused area in 19 of the 22 patients (86%), that corresponded to the infarcted regions as diagnosed by electrocardiography, coronary arteriography and left ventriculography (21 patients). The hypoperfused areas expanded after exercise in 16 of 22 patients (73%). F-18 deoxyglucose uptake was observed in these hypoperfused areas, especially in patients with hypokinetic wall motion on left ventriculography and in exercise-induced hypoperfused areas. However, positron emission tomography demonstrated diffuse uptake of F-18 deoxyglucose in 3 of 8 patients with dyskinetic wall motion. Thus, metabolically active myocardium in infarcted areas or periinfarct ischemia can be visualized with F-18 deoxyglucose and stress N-13 ammonia studies.
[(11) C]Carbon monoxide in labeling chemistry and positron emission tomography tracer development: scope and limitations.
Rahman, Obaidur
[(11) C]Carbon monoxide is an attractive precursor for labeling carbonyl position in a wide range of organic compounds. The use of [(11) C]carbon monoxide in transition metal-mediated coupling reactions has been explored by several groups during the last 15 years, and an impressive number of the synthesis of [carbonyl-(11) C]compounds have been published to date. The application of radical-mediated [(11) C]carbonylation has also been explored in some extent. However, the main limitations to apply this potential precursor in (11) C-labeling chemistry are low concentration, poor solubility in commonly used organic solvents, and low reactivity. A couple of technical solutions such as high-pressure reactor system, microfluidic system, and different approaches to confine [(11) C]CO to the reaction media at ambient pressure have been developed over the years. Although considerable advances in [(11) C]carbon monoxide chemistry have been reported in recent years, its application in positron emission tomography tracer development is still an area of work in progress. This review summarizes all contributions to the area of radiolabeling using [(11) C]carbon monoxide published between 1995 and 2014 and discusses the scope and limitations of this method in clinical positron emission tomography tracer development.
Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with (/sup 18/F)fluorodeoxyglucose
Friedland, R.P.; Budinger, T.F.; Ganz, E.; Yano, Y.; Mathis, C.A.; Koss, B.; Ober, B.A.; Huesman, R.H.; Derenzo, S.E.
Alzheimer disease is the most common cause of dementia in adults. Despite recent advances in our understanding of its anatomy and chemistry, we remain largely ignorant of its pathogenesis, physiology, diagnosis, and treatment. Dynamic positron emission tomography using (/sup 18/F)fluorodeoxyglucose (FDG) was performed on the Donner 280-crystal ring in 10 subjects with dementia of the Alzheimer type and six healthy age-matched controls. Ratios comparing mean counts per resolution element in frontal, temporoparietal, and entire cortex regions in brain sections 10 mm thick obtained 40-70 min following FDG injection showed relatively less FDG uptake in the temporoparietal cortex bilaterally in all the Alzheimer subjects (p less than 0.01). Left-right alterations were less prominent than the anteroposterior changes. This diminished uptake was due to lowered rates of FDG use and suggests that the metabolic effects of Alzheimer disease are most concentrated in the temporoparietal cortex. Positron emission tomography is a most powerful tool for the noninvasive in vivo assessment of cerebral pathophysiology in dementia.
The use of fluorine-18 fluorodeoxyglucose positron emission tomography for imaging human motor neuronal activation in the brain
The present study aimed to visualize human motor neuronal activation in the brain using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), and to develop an FDG-PET procedure for imaging neuronal activation. A male volunteer underwent 20 min periods of rest and motor activation, whilst being assessed using FDG-PET on two consecutive days. The motor task, which involved repetitively grasping and releasing the right hand, was performed during the initial 5 min of the activation period. Subtraction of the rest period signal from the activation PET images was performed using the subtraction ictal single-photon emission computed tomography co-registered to magnetic resonance imaging method. The subtracted image detected activation of the contralateral (left) primary motor cortex, supplementary motor area, and ipsilateral (right) cerebellum. In the present study, FDG-PET detected significantly increased motor-associated activation of the brain in a subject performing a motor task. PMID:26668604
Impact of technology on the utilisation of positron emission tomography in lymphoma: current and future perspectives.
Visvikis, D; Ell, P J
Positron emission tomography (PET) has now gained a place in the management of patients with cancer, including those with Hodgkin's disease and non-Hodgkin's lymphoma. Restaging studies and those addressing the monitoring of response to treatment are especially in focus. Most of the knowledge gained has been achieved with dedicated BGO-based PET technology, but there are a number of developments that will impact on the use of this metabolic imaging technique in the investigation of patients with lymphoma. The challenges ahead are determined by the need for high-quality whole-body imaging associated with increased patient throughput and the need to investigate the role of new labelled ligands. The latter are likely to yield new insights into tumour cell characterisation, tumour behaviour and tumour outcome assessment. The study of new radiolabelled ligands will impose further demands for rapid dynamic data acquisition and accurate tracer quantification. Current and future developments in PET technology range from the use of new detector materials to different detector geometries and data acquisition modes. The search for alternatives to BGO scintillation materials for PET has led to the development of PET instruments utilising new crystals such as LSO and GSO. The use of these new detectors and the increased sensitivity achieved with 3D data acquisitions represent the most significant current developments in the field. With the increasing demands imposed on the clinical utilisation of PET, issues such as study cost and patient throughput will emerge as significant future factors. As a consequence, low-cost units are being offered by the manufacturers through the utilisation of gamma camera-based SPET systems for PET coincidence imaging. Unfortunately, clinical studies in lymphoma and other cancers have already demonstrated the limitations of this technology, with 20% of lesions <15 mm in size escaping detection. On the other hand, the recent development of combined
The potential of positron emission tomography for intratreatment dynamic lung tumor tracking: A phantom study
Yang, Jaewon; Yamamoto, Tokihiro; Mazin, Samuel R.; Graves, Edward E.; Keall, Paul J.
Purpose: This study aims to evaluate the potential and feasibility of positron emission tomography for dynamic lung tumor tracking during radiation treatment. The authors propose a center of mass (CoM) tumor tracking algorithm using gated-PET images combined with a respiratory monitor and investigate the geometric accuracy of the proposed algorithm. Methods: The proposed PET dynamic lung tumor tracking algorithm estimated the target position information through the CoM of the segmented target volume on gated PET images reconstructed from accumulated coincidence events. The information was continuously updated throughout a scan based on the assumption that real-time processing was supported (actual processing time at each frame ≈10 s). External respiratory motion and list-mode PET data were acquired from a phantom programmed to move with measured respiratory traces (external respiratory motion and internal target motion) from human subjects, for which the ground truth target position was known as a function of time. The phantom was cylindrical with six hollow sphere targets (10, 13, 17, 22, 28, and 37 mm in diameter). The measured respiratory traces consisted of two sets: (1) 1D-measured motion from ten healthy volunteers and (2) 3D-measured motion from four lung cancer patients. The authors evaluated the geometric accuracy of the proposed algorithm by quantifying estimation errors (Euclidean distance) between the actual motion of targets (1D-motion and 3D-motion traces) and CoM trajectories estimated by the proposed algorithm as a function of time. Results: The time-averaged error of 1D-motion traces over all trajectories of all targets was 1.6 mm. The error trajectories decreased with time as coincidence events were accumulated. The overall error trajectory of 1D-motion traces converged to within 2 mm in approximately 90 s. As expected, more accurate results were obtained for larger targets. For example, for the 37 mm target, the average error over all 1D
The potential of positron emission tomography for intratreatment dynamic lung tumor tracking: A phantom study
Yang, Jaewon; Yamamoto, Tokihiro; Mazin, Samuel R.; Graves, Edward E.; Keall, Paul J.
Purpose: This study aims to evaluate the potential and feasibility of positron emission tomography for dynamic lung tumor tracking during radiation treatment. The authors propose a center of mass (CoM) tumor tracking algorithm using gated-PET images combined with a respiratory monitor and investigate the geometric accuracy of the proposed algorithm. Methods: The proposed PET dynamic lung tumor tracking algorithm estimated the target position information through the CoM of the segmented target volume on gated PET images reconstructed from accumulated coincidence events. The information was continuously updated throughout a scan based on the assumption that real-time processing was supported (actual processing time at each frame ≈10 s). External respiratory motion and list-mode PET data were acquired from a phantom programmed to move with measured respiratory traces (external respiratory motion and internal target motion) from human subjects, for which the ground truth target position was known as a function of time. The phantom was cylindrical with six hollow sphere targets (10, 13, 17, 22, 28, and 37 mm in diameter). The measured respiratory traces consisted of two sets: (1) 1D-measured motion from ten healthy volunteers and (2) 3D-measured motion from four lung cancer patients. The authors evaluated the geometric accuracy of the proposed algorithm by quantifying estimation errors (Euclidean distance) between the actual motion of targets (1D-motion and 3D-motion traces) and CoM trajectories estimated by the proposed algorithm as a function of time. Results: The time-averaged error of 1D-motion traces over all trajectories of all targets was 1.6 mm. The error trajectories decreased with time as coincidence events were accumulated. The overall error trajectory of 1D-motion traces converged to within 2 mm in approximately 90 s. As expected, more accurate results were obtained for larger targets. For example, for the 37 mm target, the average error over all 1D
Fast 3D-EM reconstruction using Planograms for stationary planar positron emission mammography camera.
Motta, A; Guerra, A Del; Belcari, N; Moehrs, S; Panetta, D; Righi, S; Valentini, D
At the University of Pisa we are building a PEM prototype, the YAP-PEM camera, consisting of two opposite 6 x 6 x 3 cm3 detector heads of 30 x 30 YAP:Ce finger crystals, 2 x 2 x 30 mm3 each. The camera will be equipped with breast compressors. The acquisition will be stationary. Compared with a whole body PET scanner, a planar Positron Emission Mammography (PEM) camera allows a better, easier and more flexible positioning around the breast in the vicinity of the tumor: this increases the sensitivity and solid angle coverage, and reduces cost. To avoid software rejection of data during the reconstruction, resulting in a reduced sensitivity, we adopted a 3D-EM reconstruction which uses all of the collected Lines Of Response (LORs). This skips the PSF distortion given by data rebinning procedures and/or Fourier methods. The traditional 3D-EM reconstruction requires several times the computation of the LOR-voxel correlation matrix, or probability matrix {p(ij)}; therefore is highly time-consuming. We use the sparse and symmetry properties of the matrix {p(ij)} to perform fast 3D-EM reconstruction. Geometrically, a 3D grid of cubic voxels (FOV) is crossed by several divergent 3D line sets (LORs). The symmetries occur when tracing different LORs produces the same p(ij) value. Parallel LORs of different sets cross the FOV in the same way, and the repetition of p(ij) values depends on the ratio between the tube and voxel sizes. By optimizing this ratio, the occurrence of symmetries is increased. We identify a nucleus of symmetry of LORs: for each set of symmetrical LORs we choose just one LOR to be put in the nucleus, while the others lie outside. All of the possible p(ij) values are obtainable by tracking only the LORs of this nucleus. The coordinates of the voxels of all of the other LORs are given by means of simple translation rules. Before making the reconstruction, we trace the LORs of the nucleus to find the intersecting voxels, whose p(ij) values are computed and
Myocardial Blood Flow Quantification for Evaluation of Coronary Artery Disease by Positron Emission Tomography, Cardiac Magnetic Resonance Imaging, and Computed Tomography
Waller, Alfonso H.; Blankstein, Ron; Kwong, Raymond Y.; Di Carli, Marcelo F.
The noninvasive detection of the presence and functional significance of coronary artery stenosis is important in the diagnosis, risk assessment, and management of patients with known or suspected coronary artery disease. Quantitative assessment of myocardial perfusion can provide an objective and reproducible estimate of myocardial ischemia and risk prediction. Positron emission tomography, cardiac magnetic resonance, and cardiac computed tomography perfusion are modalities capable of measuring myocardial blood flow and coronary flow reserve. In this review, we will discuss the technical aspects of quantitative myocardial perfusion imaging with positron emission tomography, cardiac magnetic resonance imaging and computed tomography, and its emerging clinical applications. PMID:24718671
(/sup 11/C)clorgyline and (/sup 11/C)-L-deprenyl and their use in measuring functional monoamine oxidase activity in the brain using positron emission tomography
Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.
This invention involves a new strategy for imaging the activity of the enzyme monoamine oxidase in the living body by using /sup 11/C-labeled enzyme inhibitors which bind irreversibly to an enzyme as a result of catalysis. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.
Adult granulosa cell tumor presenting with massive ascites, elevated CA-125 level, and low 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography
Tak, Ji Young; Park, Ji Y.; Lee, Seung Jeong; Lee, Yoon Hee; Hong, Dae Gy
Adult granulosa cell tumors (AGCTs) presenting with massive ascites and elevated serum CA-125 levels have rarely been described in the literature. An ovarian mass, massive ascites, and elevated serum CA-125 levels in postmenopausal women generally suggest a malignant ovarian tumor, particularly advanced epithelial ovarian cancer. AGCT has low 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography due to its low metabolic activity. In the present report, we describe a case of an AGCT with massive ascites, elevated serum CA-125 level, and low 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography. PMID:26430671
Synthesis and biological evaluation of fluorine-18-labeled estrogens and progestins as positron emission tomography (PET) imaging agents
VanBrocklin, H.F.
Seven new estrogen receptor-based radiopharmaceuticals, 16[alpha]-[[sup 18]F]-fluoro-17[alpha]-ethynyl-estradiol, (FEES), 15, 11[beta]-methoxy-FEES, 16, 11[beta]-ethyl-FEES, 17, 16[beta]-[[sup 18]F]-fluoroestradiol, (16[beta]-FES), 19, 11[beta]-methoxy-16[beta]-FES, 20, 16[beta]-[[sup 18]F]-fluoro-17[alpha]-ethynyl-estradiol, (16[beta]FEES), 21, and 11[beta]-methoxy-16[beta]-FEES, 22, have been prepared and evaluated as potential PET imaging agents for estrogen receptor-rich breast tumors. Radiolabeling was achieved by nucleophilic displacement of the appropriate 16[beta]- or 16[alpha]-trifluoromethanesulfonate(triflate)-estrone-3-triflate derivative with nBu[sub 4]N[sup 18]F. Subsequent hydride reduction or nucleophilic attack by lithium-trimethylsilylacetylide followed by HPLC purification yielded the FES or FEES analogs, respectively. These compounds can be prepared in 90-120 minutes from [sup 18]F-fluoride with radiochemical yields of 1-40% (decay corrected) and effective specific activities ranging from 50-4,000 Ci/mmol. The relative binding affinities (RBA) ranged from 0.5 to 309. Biological distribution was performed in 25 day old Sprague-Dawley female rats. Uterine uptake ranged from 5-16 percent of the injected dose. These fluorestrogens were highly selective in vivo as evidenced by the high uterus-to-blood (range 10-170) and uterus-to-muscle (range 25-80) ratios. The FEES analogs, 15,16, and 17, had the highest uterus to blood ratios ever seen amongst estrogen radiopharmaceuticals; 154, 145 and 169, respectively. The dose to critical clearance organs (liver and kidneys) was less than 3% of the injected dose per gram of tissue. Metabolic defluorination did not occur with these compounds. These new analogs exhibited an array of desirable characteristics for the optimal PET imaging of estrogen receptor-positive human mammary tumors.
Positron annihilation in flight
NASA Astrophysics Data System (ADS)
Tudor Jones, Goronwy
In this resource article, an exceptional bubble chamber picture - showing the annihilation of a positron (antielectron e+ ) in flight - is discussed in detail. Several other esoteric phenomena (some not easy to show on their own!) also manifest themselves in this picture - pair creation or the materialization of a high energy photon into an electron-positron pair; the `head-on' collision of a positron with an electron, from which the mass of the positron can be estimated; the Compton Effect ; an example of the emission of electromagnetic radiation (photons) by accelerating charges (bremsstrahlung ).
Kinetics of in vivo binding of antagonist to muscarinic cholinergic receptor in the human heart studied by Positron Emission Tomography
Syrota, A.; Paillotin, G.; Davy, J.M.; Aumont, M.C.
Positron Emission Tomography (PET) was used to analyze in vivo antagonist binding to human myocardial muscarinic cholinergic receptor. The methiodide salt of the muscarinic antagonist, quinuclidinyl benzilate (MQNB), was labeled with the positron emitter, Carbon-11, and injected intravenously to 8 normal subjects. /sup 11/C-MQNB concentration was determined in vivo in the ventricular septum from 40 cross-sectional images acquired at the same transverse level over a period of 70 minutes. In 4 subjects, various amounts of unlabeled atropine were rapidly injected at 20 minutes to study whether atropine competitively inhibited MQNB. The kinetics of binding of /sup 11/C-MQNB were not the same in vivo and in vitro. The apparent dissociation rate of /sup 11/C-MQNB in vivo was much slower (by 1 to 2 orders of magnitude) than that observed in vitro with /sup 3/H-QNB. After atropine injection, /sup 11/C-MQNB dissociated from its binding sites at a rate that apparently depended on the amount of atropine present. /sup 11/C-MQNB kinetics were analyzed with a mathematical model which assumes the existence of a boundary layer containing free ligand in the vicinity of the binding sites. The dissociation rate of the radioligand depends on the probability of its rebinding to a free receptor site. 11 references, 1 table.
The fast method of Cu-porphyrin complex synthesis for potential use in positron emission tomography imaging.
Kilian, Krzysztof; Pęgier, Maria; Pyrzyńska, Krystyna
Porphyrin based photosensitizers are useful agents for photodynamic therapy and fluorescence imaging of cancer. Additionally, porphyrins are excellent metal chelators, forming stable metalo-complexes and (64)Cu isotope can serve as a positron emitter (t1/2=12.7h). The other advantage of (64)Cu is its decay characteristics that facilitates the use of (64)Cu-porphyrin complex as a therapeutic agent. Thus, (64)Cu chelation with porphyrin photosensitizer may become a simple and versatile labeling strategy for clinical positron emission tomography. The present study reports a convenient method for the synthesis of Cu complex with tetrakis(4-carboxyphenyl)porphyrin (TCPP). The experimental conditions for labeling, such as the metal-to-ligand molar ratio, pH and time of reaction were optimized to achieve a high complexation efficiency in a short period of time as possible. In order to accelerate the metallation, the use of substitution reactions of cadmium or lead porphyrin and the presence of reducing agent, such as ascorbic acid, hydroxylamine and flavonoid - morin, were evaluated. The optimum conditions for the synthesis of the copper complex were borate buffer at pH9 with the addition of 10-fold molar excess, with respect to Cu(2+) ions and TCPP and ascorbic acid which resulted in reduction of the reaction time from 30 min to below 1 min.
Improved treatment planning for boron neutron capture therapy for glioblastoma multiforme using fluorine-18 labeled boronophenylalanine and positron emission tomography.
Nichols, Trent L; Kabalka, George W; Miller, Laurence F; Khan, Mohammad K; Smith, Gary T
Boron neutron capture therapy (BNCT) is a cancer brachytherapy based upon the thermal neutron reaction: 10B(n,alpha)7Li. The efficacy of the treatment depends primarily upon two conditions being met: (a) the preferential concentration of a boronated compound in the neoplasm and (b) an adequate fluence of thermal neutrons delivered to the neoplasm. The boronated amino acid, para-boronophenylalanine (BPA), is the agent widely used in clinical trials to deliver 10B to the malignancy. Positron emission tomography (PET) can be used to generate in vivo boron distribution maps by labeling BPA with the positron emitting nuclide fluorine-18. The incorporation of the PET-derived boron distribution maps into current treatment planning protocols is shown to provide improved treatment plans. Using previously established protocols, six patients with glioblastoma had 18BPA PET scans. The PET distribution maps obtained were used in the conventional BNCT treatment codes. The isodose curves derived from the PET data are shown to differ both qualitatively and quantitatively from the conventional isodose curves that were derived from calculations based upon the assumption of uniform uptake of the pharmaceutical in tumor and normal brain regions. The clinical course of each of the patients who eventually received BNCT (five of the six patients) was compared using both sets of isodose calculations. The isodose contours based upon PET derived distribution data appear to be more consistent with the patients' clinical course. PMID:12408309
(11)C[double bond, length as m-dash]O bonds made easily for positron emission tomography radiopharmaceuticals.
Rotstein, Benjamin H; Liang, Steven H; Placzek, Michael S; Hooker, Jacob M; Gee, Antony D; Dollé, Frédéric; Wilson, Alan A; Vasdev, Neil
The positron-emitting radionuclide carbon-11 ((11)C, t1/2 = 20.3 min) possesses the unique potential for radiolabeling of any biological, naturally occurring, or synthetic organic molecule for in vivo positron emission tomography (PET) imaging. Carbon-11 is most often incorporated into small molecules by methylation of alcohol, thiol, amine or carboxylic acid precursors using [(11)C]methyl iodide or [(11)C]methyl triflate (generated from [(11)C]carbon dioxide or [(11)C]methane). Consequently, small molecules that lack an easily substituted (11)C-methyl group are often considered to have non-obvious strategies for radiolabeling and require a more customized approach. [(11)C]Carbon dioxide itself, [(11)C]carbon monoxide, [(11)C]cyanide, and [(11)C]phosgene represent alternative reactants to enable (11)C-carbonylation. Methodologies developed for preparation of (11)C-carbonyl groups have had a tremendous impact on the development of novel PET tracers and provided key tools for clinical research. (11)C-Carbonyl radiopharmaceuticals based on labeled carboxylic acids, amides, carbamates and ureas now account for a substantial number of important imaging agents that have seen translation to higher species and clinical research of previously inaccessible targets, which is a testament to the creativity, utility and practicality of the underlying radiochemistry. PMID:27276357
Positron emission tomographic imaging of tumors using monoclonal antibodies. Progress report, November 1, 1992--October 31, 1993
Zalutsky, M.R.
The overall goal of this project is to be able to combine the molecular specificity of monoclonal antibodies with the imaging advantages of positron emission tomography. During the past year, were have made progress in a number of areas. This report will focus on our studies evaluating the potential of two different methods for labeling a monoclonal antibody fragment with positron-emitting F-18 both in vitro and in athymic mice bearing subcutaneous D-54 MG human glioma xenografts. The F (a b{prime}){sub 2} fragment of Me1-14, a murine egg{sub 2a} reactive with an epitope of the tumor associated proteoglycan sulfate present in gliomas and melanomas, was used. This antibody is a particular interest because of our ongoing clinical radioimmunotherapy trails using Me1--14 that could ultimately benefit from the determination of quantitative dosimetry using monoclonal antibody PET imaging. Our results demonstrated, for the first time, that MAb fragments could be labeled with F-18 with retention of immunoreactivity and affinity. Further, they show that selective and specific tumor uptake of an F-18 labeled MAb fragment can be achieved in a xenograft model in a time frame compatible with the short half life of this nuclide.
The fast method of Cu-porphyrin complex synthesis for potential use in positron emission tomography imaging
NASA Astrophysics Data System (ADS)
Kilian, Krzysztof; Pęgier, Maria; Pyrzyńska, Krystyna
Porphyrin based photosensitizers are useful agents for photodynamic therapy and fluorescence imaging of cancer. Additionally, porphyrins are excellent metal chelators, forming stable metalo-complexes and 64Cu isotope can serve as a positron emitter (t1/2 = 12.7 h). The other advantage of 64Cu is its decay characteristics that facilitates the use of 64Cu-porphyrin complex as a therapeutic agent. Thus, 64Cu chelation with porphyrin photosensitizer may become a simple and versatile labeling strategy for clinical positron emission tomography. The present study reports a convenient method for the synthesis of Cu complex with tetrakis(4-carboxyphenyl)porphyrin (TCPP). The experimental conditions for labeling, such as the metal-to-ligand molar ratio, pH and time of reaction were optimized to achieve a high complexation efficiency in a short period of time as possible. In order to accelerate the metallation, the use of substitution reactions of cadmium or lead porphyrin and the presence of reducing agent, such as ascorbic acid, hydroxylamine and flavonoid - morin, were evaluated. The optimum conditions for the synthesis of the copper complex were borate buffer at pH 9 with the addition of 10-fold molar excess, with respect to Cu2 + ions and TCPP and ascorbic acid which resulted in reduction of the reaction time from 30 min to below 1 min.
Positron emission tomography/magnetic resonance hybrid scanner imaging of cerebral blood flow using 15O-water positron emission tomography and arterial spin labeling magnetic resonance imaging in newborn piglets
Andersen, Julie B; Henning, William S; Lindberg, Ulrich; Ladefoged, Claes N; Højgaard, Liselotte; Greisen, Gorm; Law, Ian
Abnormality in cerebral blood flow (CBF) distribution can lead to hypoxic–ischemic cerebral damage in newborn infants. The aim of the study was to investigate minimally invasive approaches to measure CBF by comparing simultaneous 15O-water positron emission tomography (PET) and single TI pulsed arterial spin labeling (ASL) magnetic resonance imaging (MR) on a hybrid PET/MR in seven newborn piglets. Positron emission tomography was performed with IV injections of 20 MBq and 100 MBq 15O-water to confirm CBF reliability at low activity. Cerebral blood flow was quantified using a one-tissue-compartment-model using two input functions: an arterial input function (AIF) or an image-derived input function (IDIF). The mean global CBF (95% CI) PET-AIF, PET-IDIF, and ASL at baseline were 27 (23; 32), 34 (31; 37), and 27 (22; 32) mL/100 g per minute, respectively. At acetazolamide stimulus, PET-AIF, PET-IDIF, and ASL were 64 (55; 74), 76 (70; 83) and 79 (67; 92) mL/100 g per minute, respectively. At baseline, differences between PET-AIF, PET-IDIF, and ASL were 22% (P<0.0001) and −0.7% (P=0.9). At acetazolamide, differences between PET-AIF, PET-IDIF, and ASL were 19% (P=0.001) and 24% (P=0.0003). In conclusion, PET-IDIF overestimated CBF. Injected activity of 20 MBq 15O-water had acceptable concordance with 100 MBq, without compromising image quality. Single TI ASL was questionable for regional CBF measurements. Global ASL CBF and PET CBF were congruent during baseline but not during hyperperfusion. PMID:26058699
Zolpidem-Induced Arousal by Paradoxical GABAergic Stimulation: A Case Report With F-18 Flumazenil Positron Emission Tomography and Single Photon Emission Computed Tomography Study
Kim, Changjae; Nam, Ki Yeun; Park, Jin Woo; Lee, Ho Jun
Zolpidem is a non-benzodiazepine drug that has selectivity for the gamma-aminobutyric acid (GABA) receptors. We experienced paradoxical effect of zolpidem in a 48-year-old male patient with hypoxic-ischemic brain injury after cardiac arrest. The patient was in stupor and could not communicate. His Glasgow Coma Scale (GCS) was E2M4V2 and Rancho Los Amigos (RLA) was grade III to IV. Zolpidem was prescribed to induce sedation but paradoxically, he became alert (GCS 15, RLA VII) and was able to communicate. The arousal lasted for 2 hours repeatedly following each administration of the medication. While he was alert, electroencephalogram showed the reversal of slow wave into beta range fast activity and F-18 flumazenil positron emission tomography (PET) showed increased GABAergic receptor activity in both frontoparietotemporal cortices. Single photon emission computed tomography (SPECT) also showed increased cerebral perfusion and reversal of cerebellar diaschisis. PMID:26949686
An introduction to the physics and instrumentation of positron emission tomography
Bennett, G.W.
Positron-emitting radionuclides permit the use of electronic collimation and thus achieve higher resolution and better sensitivity than can be obtained with gamma-emitting radiotracers. The evolution of PET imaging systems can be traced from the use of opposed collimated scanning detectors, which had all the limitations of traditional single photon imaging devices, to the present systems which surround the subject with a large volume of detector material. The improvements in system resolution now approach the theoretical limitation imposed by positron-range, and angular deviation. The use of coding permits the use of shared electronics for reading our multiple detectors, which promises to decrease the cost of PET imaging devices, at some penalty of degraded performance. Improvements in computer architectures and capabilities permit faster reconstruction of the multiple planes imaged by multi-slice imaging systems. Software for distortion correction and image processing are still under development, and the ability to map between different devices requires the coordination of efforts between different groups in the same institution. The development and validation of the mathematical models for tracer kinetic analyses will continue to occupy the attention of clinicians and scientists involved in these developments. The desire to make these devices simple and cheap enough to be used in routine patient care is occupying the attention of industry and pioneering users, but this goal has not yet been achieved. 17 refs., 15 figs., 3 tabs.
Are we ready for positron emission tomography/computed tomography-based target volume definition in lymphoma radiation therapy?
Yeoh, Kheng-Wei; Mikhaeel, N George
Fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has become indispensable for the clinical management of lymphomas. With consistent evidence that it is more accurate than anatomic imaging in the staging and response assessment of many lymphoma subtypes, its utility continues to increase. There have therefore been efforts to incorporate PET/CT data into radiation therapy decision making and in the planning process. Further, there have also been studies investigating target volume definition for radiation therapy using PET/CT data. This article will critically review the literature and ongoing studies on the above topics, examining the value and methods of adding PET/CT data to the radiation therapy treatment algorithm. We will also discuss the various challenges and the areas where more evidence is required.
Development of new deoxycytidine kinase inhibitors and non-invasive in vivo evaluation using Positron Emission Tomography
Murphy, Jennifer M.; Armijo, Amanda L.; Nomme, Julian; Lee, Chi Hang; Smith, Quentin A.; Li, Zheng; Campbell, Dean O.; Liao, Hsiang-I; Nathanson, David A.; Austin, Wayne R.; Lee, Jason T.; Darvish, Ryan; Wei, Liu; Wang, Jue; Su, Ying; Damoiseaux, Robert; Sadeghi, Saman; Phelps, Michael E.; Herschman, Harvey R.; Czernin, Johannes; Alexandrova, Anastassia N.; Jung, Michael E.; Lavie, Arnon; Radu, Caius G.
Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest and apoptosis. Evidence implicating dCK in cancer cell proliferation and survival stimulated our interest in developing small molecule dCK inhibitors. Following a high throughput screen of a diverse chemical library, a structure-activity relationship study was carried out. Positron Emission Tomography (PET) using 18F-L-1-(2′-deoxy-2′-FluoroArabinofuranosyl) Cytosine (18F-L-FAC), a dCK-specific substrate, was used to rapidly rank lead compounds based on their ability to inhibit dCK activity in vivo. Evaluation of a subset of the most potent compounds in cell culture (IC50 = ∼1 – 12 nM) using the 18F-L-FAC PET pharmacodynamic assay identified compounds demonstrating superior in vivo efficacy. PMID:23947754
Acute Calculous Cholecystitis Missed on Computed Tomography and Ultrasound but Diagnosed with Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography
Aparici, Carina Mari; Win, Aung Zaw
We present a case of a 69-year-old patient who underwent ascending aortic aneurysm repair with aortic valve replacement. On postsurgical day 12, he developed leukocytosis and low-grade fevers. The chest computed tomography (CT) showed a periaortic hematoma which represents a postsurgical change from aortic aneurysm repair, and a small pericardial effusion. The abdominal ultrasound showed cholelithiasis without any sign of cholecystitis. Finally, a fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT examination was ordered to find the cause of fever of unknown origin, and it showed increased FDG uptake in the gallbladder wall, with no uptake in the lumen. FDG-PET/CT can diagnose acute cholecystitis in patients with nonspecific clinical symptoms and laboratory results. PMID:27625897
A rare cardiac haemangioma in the right ventricle diagnosed accurately using ¹⁸F-fluorodeoxyglucose-positron emission tomography.
Matsuba, Tomoyuki; Hisashi, Yosuke; Yotsumoto, Goichi; Imoto, Yutaka
A right ventricular cardiac tumour was incidentally detected in a 61-year-old man during a preoperative examination for coronary artery bypass grafting (CABG). Findings on computed tomography and magnetic resonance imaging suggested the differential diagnoses of myxoma, haemangioma and haemangiosarcoma, and it was difficult to identify whether the tumour was benign or malignant. (18)F-fluorodeoxyglucose-positron emission tomography strongly suggested a benign tumour. We enucleated the tumour, because an intraoperative frozen section also strongly suggested a benign origin. After resection, CABG under cardiopulmonary bypass was performed. Histopathological and immunohistochemical analysis indicated a cavernous haemangioma without evidence of malignant tissue. The patient has survived 20 months after surgery with no evidence of tumour recurrence.
Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Findings of Post Traumatic Lymphangioma in a Young Adult Male
Kwon, Sang Don; Chun, Kyung Ah; Kong, Eun Jung; Cho, Ihn Ho
The authors report the case of a 34-year-old male, who underwent a fluorine-18 fluoro deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scan 7 years after trauma for the evaluation of multifocal masses in the right iliac and right inguinal areas. CT findings showed multifocal low density masses and 18F-FDG PET revealed slightly increased uptake (maximum standardized uptake value [SUVmax] 3.1). These findings did not exclude the possibility of a benign or malignant lesion. To achieve differential diagnosis, partial surgical excision was performed and a pathologic examination subsequently revealed lymphangioma. Here, the authors describe the 18F-FDG PET/CT findings of a rare case of lymphangioma resulting from trauma. PMID:27699163
Acute Calculous Cholecystitis Missed on Computed Tomography and Ultrasound but Diagnosed with Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography.
Aparici, Carina Mari; Win, Aung Zaw
We present a case of a 69-year-old patient who underwent ascending aortic aneurysm repair with aortic valve replacement. On postsurgical day 12, he developed leukocytosis and low-grade fevers. The chest computed tomography (CT) showed a periaortic hematoma which represents a postsurgical change from aortic aneurysm repair, and a small pericardial effusion. The abdominal ultrasound showed cholelithiasis without any sign of cholecystitis. Finally, a fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT examination was ordered to find the cause of fever of unknown origin, and it showed increased FDG uptake in the gallbladder wall, with no uptake in the lumen. FDG-PET/CT can diagnose acute cholecystitis in patients with nonspecific clinical symptoms and laboratory results. PMID:27625897
Acute Calculous Cholecystitis Missed on Computed Tomography and Ultrasound but Diagnosed with Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography
Aparici, Carina Mari; Win, Aung Zaw
We present a case of a 69-year-old patient who underwent ascending aortic aneurysm repair with aortic valve replacement. On postsurgical day 12, he developed leukocytosis and low-grade fevers. The chest computed tomography (CT) showed a periaortic hematoma which represents a postsurgical change from aortic aneurysm repair, and a small pericardial effusion. The abdominal ultrasound showed cholelithiasis without any sign of cholecystitis. Finally, a fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT examination was ordered to find the cause of fever of unknown origin, and it showed increased FDG uptake in the gallbladder wall, with no uptake in the lumen. FDG-PET/CT can diagnose acute cholecystitis in patients with nonspecific clinical symptoms and laboratory results.
"Mixed" anionic and non-ionic micellar liquid chromatography for high-speed radiometabolite analysis of positron emission tomography radioligands.
Nakao, Ryuji; Halldin, Christer
A mixed micellar liquid chromatographic (LC) method, the mobile phase consisting of anionic and non-ionic surfactants, has been developed for the high-speed direct radiometabolite analysis of positron emission tomography (PET) radioligands in plasma. The addition of Triton X-100 on an anionic surfactant sodium dodecyl sulphate (SDS) mobile phase improved elution strength and peak efficiency for many PET radioligands. Several radioligands could be easily separated from their radioactive metabolites with short run time of only 4 min using a "pure" (without organic solvent) mixed micellar mobile phase and semi-preparative monolithic C(18)-bonded silica column by simple isocratic elution without any treatment of plasma. Moreover, the use of "hybrid" mixed micellar mobile phase containing anionic, non-ionic surfactants and organic solvent was effective to further enhance peak efficiency and elute highly retained hydrophobic PET radioligands. These characteristics enabled significant shorting the radiometabolite analysis procedure of PET radioligands and simplifying the experimental setup.
Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Findings of Post Traumatic Lymphangioma in a Young Adult Male
Kwon, Sang Don; Chun, Kyung Ah; Kong, Eun Jung; Cho, Ihn Ho
The authors report the case of a 34-year-old male, who underwent a fluorine-18 fluoro deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scan 7 years after trauma for the evaluation of multifocal masses in the right iliac and right inguinal areas. CT findings showed multifocal low density masses and 18F-FDG PET revealed slightly increased uptake (maximum standardized uptake value [SUVmax] 3.1). These findings did not exclude the possibility of a benign or malignant lesion. To achieve differential diagnosis, partial surgical excision was performed and a pathologic examination subsequently revealed lymphangioma. Here, the authors describe the 18F-FDG PET/CT findings of a rare case of lymphangioma resulting from trauma.
Synthesis and evaluation of fluorinated fingolimod (FTY720) analogues for sphingosine-1-phosphate receptor molecular imaging by positron emission tomography.
Shaikh, Rizwan S; Schilson, Stefanie S; Wagner, Stefan; Hermann, Sven; Keul, Petra; Levkau, Bodo; Schäfers, Michael; Haufe, Günter
Sphingosine-1-phosphate (S1P) is a lysophospholipid that evokes a variety of biological responses via stimulation of a set of cognate G-protein coupled receptors (GPCRs): S1P1-S1P5. S1P and its receptors (S1PRs) play important roles in the immune, cardiovascular, and central nervous systems and have also been implicated in carcinogenesis. Recently, the S1P analogue Fingolimod (FTY720) has been approved for the treatment of patients with relapsing multiple sclerosis. This work presents the synthesis of various fluorinated structural analogues of FTY720, their in vitro and in vivo biological testing, and their development and application as [(18)F]radiotracers for the study of S1PR biodistribution and imaging in mice using small-animal positron emission tomography (PET).
Bilateral Diffuse Fluorodeoxyglucose Uptake in Thyroid Gland Diagnosed by Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography
Win, Aung Zaw; Aparici, Carina Mari
Our patient is a female who was first diagnosed with breast cancer at the age of 23. A follow-up fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) at age 44 revealed diffuse high FDG uptake in an enlarged thyroid gland. Fine-needle aspiration (FNA) of the thyroid mass revealed estrogen receptor/progesterone receptor negative, human epidermal growth factor receptor 2+ breast cancer. To the best of our knowledge, this is the first case to report breast cancer metastasis to the thyroid in a diffuse pattern on FDG-PET/CT. Bilateral diffuse uptake of FDG in thyroid is the most commonly associated with benign conditions. However, FNA biopsies need to be done to rule out metastatic disease in thyroid lesions with diffuse high FDG uptake, especially for patients with history of cancer. PMID:25191131
18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging findings of primary intracranial histiocytic sarcoma in a dog.
Kang, Byeong-Teck; Park, Chul; Yoo, Jong-Hyun; Gu, Su-Hyun; Jang, Dong-Pyo; Kim, Young-Bo; Woo, Eung-Je; Kim, Dae-Young; Cho, Zang-Hee; Park, Hee-Myung
A 10-year-old, neutered male, Maltese dog presented with a three week history of intention tremor, right hind limb rigidity, poor coordination, and occasional circling to the left. On magnetic resonance imaging (MRI) of the brain, a mass was identified in the right occipital lobe and cerebellum. Three weeks after the initial MRI scan, we performed an (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) of the brain. The FDG-PET demonstrated areas of hypermetabolism in the right occipital lobe, cerebellum, pons, and medulla oblongata. When the standardized uptake value was calculated, the hypermetabolic lesion was higher than the gray matter values. The anatomical location of the hypermetabolic lesion was more precisely identified by the PET-MRI fusion images. The dog was definitively diagnosed as a primary histiocytic sarcoma of the brain. This is the first report of PET findings of an intracranial histiocytic sarcoma in a dog.
Design of brain imaging agents for positron emission tomography: do large bioconjugates provide an opportunity for in vivo brain imaging?
Schirrmacher, Ralf; Bernard-Gauthier, Vadim; Reader, Andrew; Soucy, Jean-Paul; Schirrmacher, Esther; Wängler, Björn; Wängler, Carmen
The development of brain imaging agents for positron emission tomography and other in vivo imaging modalities mostly relies on small compounds of low MW as a result of the restricted transport of larger molecules, such as peptides and proteins, across the blood-brain barrier. Besides passive transport, only a few active carrier mechanisms, such as glucose transporters and amino acid transporters, have so far been exploited to mediate the accumulation of imaging probes in the brain. An important question for the future is whether some of the abundant active carrier systems located at the blood-brain barrier can be used to shuttle potential, but non-crossing, imaging agents into the brain. What are the biological and chemical constrictions toward such bioconjugates and is it worthwhile to persue such a delivery strategy?
Positron emission tomography and drug discovery: contributions to the understanding of pharmacokinetics, mechanism of action and disease state characterization.
Klimas, Michael T
As an imaging modality, positron emission tomography (PET) provides unique quantitative in vivo information of value to drug discovery studies. These non-invasive studies span the pharmacokinetic/pharmacodynamic evaluation of potential drug candidates, receptor occupancy as an important determinant of efficacy, the pharmacological characterization of potential mechanisms of action, and the biological characterization of disease with well-characterized PET ligands. PET techniques are also being applied to the assessment of gene-level activities and the longitudinal evaluation of disease progression and therapeutic intervention. As the availability of PET scanners, cyclotrons, and specific PET ligands grows, the techniques highlighted in this review will become central to target validation, drug candidate selection, pharmacokinetic characterization, and clinical evaluation.
Are We Ready for Positron Emission Tomography/Computed Tomography-based Target Volume Definition in Lymphoma Radiation Therapy?
Yeoh, Kheng-Wei; Mikhaeel, N. George
Fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has become indispensable for the clinical management of lymphomas. With consistent evidence that it is more accurate than anatomic imaging in the staging and response assessment of many lymphoma subtypes, its utility continues to increase. There have therefore been efforts to incorporate PET/CT data into radiation therapy decision making and in the planning process. Further, there have also been studies investigating target volume definition for radiation therapy using PET/CT data. This article will critically review the literature and ongoing studies on the above topics, examining the value and methods of adding PET/CT data to the radiation therapy treatment algorithm. We will also discuss the various challenges and the areas where more evidence is required.
Bitemporal hypometabolism in Creutzfeldt-Jakob disease measured by positron emission tomography with (/sup 18/F)-2-fluorodeoxyglucose
Friedland, R.P.; Prusiner, S.B.; Jagust, W.J.; Budinger, T.F.; Davis, R.L.
It is well established that Creutzfeldt-Jakob disease (CJD) is caused by a slow infectious agent similar to the scrapie prion. However, the pathogenesis of this infection is poorly understood. Positron emission tomography (PET) was performed on a 54-year-old man with autopsy confirmed CJD using (18F)-2-fluorodeoxyglucose (FDG) and the Donner 280-crystal tomograph. Temporal lobe hypometabolism with hemispheric asymmetry was observed. These findings are similar to those previously obtained in PET-FDG studies of patients with clinically defined Alzheimer disease (AD). The similarities in the regional metabolic alterations between CJD and AD provide additional evidence for the possibility that AD may be caused by a slow infectious prion.
SensL B-Series and C-Series silicon photomultipliers for time-of-flight positron emission tomography
NASA Astrophysics Data System (ADS)
O`Neill, K.; Jackson, C.
Silicon photomultipliers from SensL are designed for high performance, uniformity and low cost. They demonstrate peak photon detection efficiency of 41% at 420 nm, which is matched to the output spectrum of cerium doped lutetium orthosilicate. Coincidence resolving time of less than 220 ps is demonstrated. New process improvements have lead to the development of C-Series SiPM which reduces the dark noise by over an order of magnitude. In this paper we will show characterization test results which include photon detection efficiency, dark count rate, crosstalk probability, afterpulse probability and coincidence resolving time comparing B-Series to the newest pre-production C-Series. Additionally we will discuss the effect of silicon photomultiplier microcell size on coincidence resolving time allowing the optimal microcell size choice to be made for time of flight positron emission tomography systems.
A comparison of positron emission particle tracking (PEPT) methods for analysis of a tube-in-shell heat exchanger
NASA Astrophysics Data System (ADS)
Wiggins, Cody; Patel, Nitant; Ruggles, Arthur
A positron emission particle tracking (PEPT) study of a stainless steel tube-in-shell heat exchanger is performed. Studies are performed using two different energy window settings. A new multiple particle tracking technique is introduced and used in this analysis. Results are compared to those obtained with previously established multiple particle tracking technique. Both techniques are found to be capable of flow imaging through opaque surfaces. No significant difference is observed between energy window settings using either method. Results from both methods are found to be qualitatively similar; however, it is observed that the new method exhibits consistently lower measurement uncertainty across the field of view of the scanner and is robust against the adverse effects of stationary particles in the flow field.
Synthesis and evaluation of fluorinated fingolimod (FTY720) analogues for sphingosine-1-phosphate receptor molecular imaging by positron emission tomography.
Shaikh, Rizwan S; Schilson, Stefanie S; Wagner, Stefan; Hermann, Sven; Keul, Petra; Levkau, Bodo; Schäfers, Michael; Haufe, Günter
Sphingosine-1-phosphate (S1P) is a lysophospholipid that evokes a variety of biological responses via stimulation of a set of cognate G-protein coupled receptors (GPCRs): S1P1-S1P5. S1P and its receptors (S1PRs) play important roles in the immune, cardiovascular, and central nervous systems and have also been implicated in carcinogenesis. Recently, the S1P analogue Fingolimod (FTY720) has been approved for the treatment of patients with relapsing multiple sclerosis. This work presents the synthesis of various fluorinated structural analogues of FTY720, their in vitro and in vivo biological testing, and their development and application as [(18)F]radiotracers for the study of S1PR biodistribution and imaging in mice using small-animal positron emission tomography (PET). PMID:25826109
One-step synthesis of 4-[(18) F]fluorobenzyltriphenylphosphonium cation for imaging with positron emission tomography.
Zhang, Zhengxing; Zhang, Chengcheng; Lau, Joseph; Colpo, Nadine; Bénard, François; Lin, Kuo-Shyan
4-[(18) F]Fluorobenzyltriphenylphosphonium cation ((18) F-FBnTP) is a promising negative membrane potential targeting positron emission tomography tracer. However, the reported multistep radiolabeling approach for the synthesis of (18) F-FBnTP poses a challenge for routine clinical applications. In this study, we demonstrated that (18) F-FBnTP can be prepared in good conversion yields (~60%, nondecay corrected) in just one step via a copper-mediated (18) F-fluorination reaction using a pinacolyl arylboronate precursor. In addition, our data suggest that (18) F-labeled (phosphonium) cations can be efficiently prepared via a copper-mediated (18) F-fluoronation by using triflate as the counterion.
Use of 18F-2-Fluorodeoxyglucose to Label Antibody Fragments for Immuno-Positron Emission Tomography of Pancreatic Cancer
We generated 18F-labeled antibody fragments for positron emission tomography (PET) imaging using a sortase-mediated reaction to install a trans-cyclooctene-functionalized short peptide onto proteins of interest, followed by reaction with a tetrazine-labeled-18F-2-deoxyfluoroglucose (FDG). The method is rapid, robust, and site-specific (radiochemical yields > 25%, not decay corrected). The availability of 18F-2-deoxyfluoroglucose avoids the need for more complicated chemistries used to generate carbon–fluorine bonds. We demonstrate the utility of the method by detecting heterotopic pancreatic tumors in mice by PET, using anti-Class II MHC single domain antibodies. We correlate macroscopic PET images with microscopic two-photon visualization of the tumor. Our approach provides easy access to 18F-labeled antibodies and their fragments at a level of molecular specificity that complements conventional 18F-FDG imaging. PMID:26955657
Optimization of [(11)C]raclopride positron emission tomographic rat studies: comparison of methods for image quantification.
Torrent, Elia; Farré, Magí; Abasolo, Ibane; Millan, Olga; Llop, Jordi; Gispert, Juan Domingo; Ruiz, Alba; Pareto, Deborah
The goal of this study was to compare different quantification approaches and reconstruction methods to estimate the binding potential in [11C]raclopride studies in rats. The final aim was to determine if the results obtained with short-acquisition scanning were comparable to the results obtained with long-acquistion (conventional) scanning. We analyzed two rat data sets: a baseline versus a pretreatment study (with cold raclopride) and a young versus an old animal group comparison. The study results support the contention that optimization of [11C]raclopride positron emission tomographic studies in rats by shortening the acquisition time is feasible. In addition, filtered backprojection is recommended as a reconstruction algorithm, although iterative methods may be more sensitive to detect within-group differences.
Imaging Spectrum and Pitfalls of 11C-Methionine Positron Emission Tomography in a Series of Patients with Intracranial Lesions
Matsuda, Hiroshi; Kubota, Kazoo
11C-methionine (Met) positron emission tomography (PET) is one of the most commonly used PET tracers for evaluating brain tumors. However, few reports have described tips and pitfalls of 11C-Met PET for general practitioners. Physiological 11C-Met uptake, anatomical variations, vascular disorders, non-tumorous lesions such as inflammation or dysplasia, benign brain tumors and patient condition during 11C-Met PET examination can potentially affect the image interpretation and cause false positives and negatives. These pitfalls in the interpretation of 11C-Met PET images are important for not only nuclear medicine physicians but also general radiologists. Familiarity with the spectrum and pitfalls of 11C-Met images could help prevent unfavorable clinical results caused by misdiagnoses. PMID:27134530
Positron emission tomography correlates of visually-scored electroencephalographic waveforms during non-Rapid Eye Movement sleep.
Picchioni, Dante; Killgore, William D S; Balkin, Thomas J; Braun, Allen R
Visually-scored, non-Rapid Eye Movement (REM) sleep electroencephalographic (EEG) waveform activity for each 30-s sleep scored epoch-including the number of sleep spindles, the number of K-complexes, and the percentage of delta waves occupying the epoch-was correlated with H(2)(15)O positron emission tomography. Sleep spindle correlations included positive correlations in the thalamus and right hippocampus. K-complex correlations included positive correlations in the frontomedian prefrontal cortex and cerebellum. Delta wave correlations included negative correlations in the thalamus, frontomedian prefrontal cortex, dorsal pons, and primary visual cortex. Each pattern of correlations may suggest a functional significance for these waveforms that relates to a waking outcome.
/sup 18/F-2-deoxy-2-fluoro-D-glucose as a tracer in the positron emission tomographic study of senile dementia
Farkas, T.; Ferris, S.H.; Wolf, A.P.; De Leon, M.J.; Christman, D.R.; Reisberg, B.; Alavi, A.; Fowler, J.S.; George, A.E.; Reivich, M.
Using /sup 18/F-2-deoxy-2-fluoro-D-glucose as a tracer, the authors obtained positron emission tomographic scans of 11 patients with senile dementia and 6 age-matched controls. The rate of glucose metabolism was significantly lower in the patients with senile dementia and significantly correlated with the degree of cognitive impairment.
Sodium-22-radiolabeled silica nanoparticles as new radiotracer for biomedical applications: in vivo positron emission tomography imaging, biodistribution, and biocompatibility
Al Faraj, Achraf; Alotaibi, Basem; Shaik, Abjal Pasha; Shamma, Khaled Z; Al Jammaz, Ibrahim; Gerl, Jürgen
Despite their advantageous chemical properties for nuclear imaging, radioactive sodium-22 (22Na) tracers have been excluded for biomedical applications because of their extremely long lifetime. In the current study, we proposed, for the first time, the use of 22Na radiotracers for pre-clinical applications by efficiently loading with silica nanoparticles (SiNPs) and thus offering a new life for this radiotracer. Crown-ether-conjugated SiNPs (300 nm; −0.18±0.1 mV) were successfully loaded with 22Na with a loading efficacy of 98.1%±1.4%. Noninvasive positron emission tomography imaging revealed a transient accumulation of 22Na-loaded SiNPs in the liver and to a lower extent in the spleen, kidneys, and lung. However, the signal gradually decreased in a time-dependent manner to become not detectable starting from 2 weeks postinjection. These observations were confirmed ex vivo by quantifying 22Na radioactivity using γ-counter and silicon content using inductively coupled plasma-mass spectrometry in the blood and the different organs of interest. Quantification of Si content in the urine and feces revealed that SiNPs accumulated in the organs were cleared from the body within a period of 2 weeks and completely in 1 month. Biocompatibility evaluations performed during the 1-month follow-up study to assess the possibility of synthesized nanocarriers to induce oxidative stress or DNA damage confirmed their safety for pre-clinical applications. 22Na-loaded nanocarriers can thus provide an innovative diagnostic agent allowing ultra-sensitive positron emission tomography imaging. On the other hand, with its long lifetime, onsite generators or cyclotrons will not be required as 22Na can be easily stored in the nuclear medicine department and be used on-demand. PMID:26504381
Mathematical modeling of positron emission tomography (PET) data to assess radiofluoride transport in living plants following petiolar administration
Converse, Alexander K.; Ahlers, Elizabeth O.; Bryan, Tom W.; Hetue, Jackson D.; Lake, Katherine A.; Ellison, Paul A.; Engle, Jonathan W.; Barnhart, Todd E.; Nickles, Robert J.; Williams, Paul H.; et al
Background: Ion transport is a fundamental physiological process that can be studied non-invasively in living plants with radiotracer imaging methods. Fluoride is a known phytotoxic pollutant and understanding its transport in plants after leaf absorption is of interest to those in agricultural areas near industrial sources of airborne fluoride. Here we report the novel use of a commercial, high-resolution, animal positron emission tomography (PET) scanner to trace a bolus of [¹⁸F]fluoride administered via bisected petioles of Brassica oleracea, an established model species, to simulate whole plant uptake of atmospheric fluoride. This methodology allows for the first time mathematical compartmental modelingmore » of fluoride transport in the living plant. Radiotracer kinetics in the stem were described with a single-parameter free- and trapped-compartment model and mean arrival times at different stem positions were calculated from the free-compartment time-activity curves. Results: After initiation of administration at the bisected leaf stalk, [¹⁸F] radioactivity climbed for approximately 10 minutes followed by rapid washout from the stem and equilibration within leaves. Kinetic modeling of transport in the stem yielded a trapping rate of 1.5 +/- 0.3%/min (mean +/- s.d., n = 3), velocity of 2.2 +/- 1.1 cm/min, and trapping fraction of 0.8 +/- 0.5%/cm. Conclusion: Quantitative assessment of physiologically meaningful transport parameters of fluoride in living plants is possible using standard positron emission tomography in combination with petiolar radiotracer administration. Movement of free fluoride was observed to be consistent with bulk flow in xylem, namely a rapid and linear change in position with respect to time. Trapping, likely in the apoplast, was observed. Future applications of the methods described here include studies of transport of other ions and molecules of interest in plant physiology.« less
Mathematical modeling of positron emission tomography (PET) data to assess radiofluoride transport in living plants following petiolar administration
Converse, Alexander K.; Ahlers, Elizabeth O.; Bryan, Tom W.; Hetue, Jackson D.; Lake, Katherine A.; Ellison, Paul A.; Engle, Jonathan W.; Barnhart, Todd E.; Nickles, Robert J.; Williams, Paul H.; DeJesus, Onofre T.
Background: Ion transport is a fundamental physiological process that can be studied non-invasively in living plants with radiotracer imaging methods. Fluoride is a known phytotoxic pollutant and understanding its transport in plants after leaf absorption is of interest to those in agricultural areas near industrial sources of airborne fluoride. Here we report the novel use of a commercial, high-resolution, animal positron emission tomography (PET) scanner to trace a bolus of [¹⁸F]fluoride administered via bisected petioles of Brassica oleracea, an established model species, to simulate whole plant uptake of atmospheric fluoride. This methodology allows for the first time mathematical compartmental modeling of fluoride transport in the living plant. Radiotracer kinetics in the stem were described with a single-parameter free- and trapped-compartment model and mean arrival times at different stem positions were calculated from the free-compartment time-activity curves. Results: After initiation of administration at the bisected leaf stalk, [¹⁸F] radioactivity climbed for approximately 10 minutes followed by rapid washout from the stem and equilibration within leaves. Kinetic modeling of transport in the stem yielded a trapping rate of 1.5 +/- 0.3%/min (mean +/- s.d., n = 3), velocity of 2.2 +/- 1.1 cm/min, and trapping fraction of 0.8 +/- 0.5%/cm. Conclusion: Quantitative assessment of physiologically meaningful transport parameters of fluoride in living plants is possible using standard positron emission tomography in combination with petiolar radiotracer administration. Movement of free fluoride was observed to be consistent with bulk flow in xylem, namely a rapid and linear change in position with respect to time. Trapping, likely in the apoplast, was observed. Future applications of the methods described here include studies of transport of other ions and molecules of interest in plant physiology.
The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five-point scale
Gallamini, Andrea; Barrington, Sally F.; Biggi, Alberto; Chauvie, Stephane; Kostakoglu, Lale; Gregianin, Michele; Meignan, Michel; Mikhaeel, George N.; Loft, Annika; Zaucha, Jan M.; Seymour, John F.; Hofman, Michael S.; Rigacci, Luigi; Pulsoni, Alessandro; Coleman, Morton; Dann, Eldad J.; Trentin, Livio; Casasnovas, Olivier; Rusconi, Chiara; Brice, Pauline; Bolis, Silvia; Viviani, Simonetta; Salvi, Flavia; Luminari, Stefano; Hutchings, Martin
A retrospective, international, multicenter study was undertaken to assess: (i) the prognostic role of 'interim' positron emission tomography performed during treatment with doxorubicin, bleomycin, vinblastine and dacarbazine in patients with Hodgkin lymphoma; and (ii) the reproducibility of the Deauville five-point scale for the interpretation of interim positron emission tomography scan. Two hundred and sixty patients with newly diagnosed Hodgkin lymphoma were enrolled. Fifty-three patients with early unfavorable and 207 with advanced-stage disease were treated with doxorubicin, bleomycin, vinblastine and dacarbazine ± involved-field or consolidation radiotherapy. Positron emission tomography scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. An international panel of six expert reviewers independently reported the scans using the Deauville five-point scale, blinded to treatment outcome. Forty-five scans were scored as positive (17.3%) and 215 (82.7%) as negative. After a median follow up of 37.0 (2–110) months, 252 patients are alive and eight have died. The 3-year progression-free survival rate was 83% for the whole study population, 28% for patients with interim positive scans and 95% for patients with interim negative scans (P<0.0001). The sensitivity, specificity, and negative and positive predictive values of interim positron emission tomography scans for predicting treatment outcome were 0.73, 0.94, 0.94 and 0.73, respectively. Binary concordance amongst reviewers was good (Cohen's kappa 0.69–0.84). In conclusion, the prognostic role and validity of the Deauville five-point scale for interpretation of interim positron emission tomography scans have been confirmed by the present study. PMID:24658820