post - implant quality assessment is important to ensure that the radiation dose adequately covers the prostate and is acceptable in nearby critical structures . implant quality can be represented by dose - volume histogram ( dvh ) parameters , which correlate with biochemical control and survival [ 1 , 2 , 3 , 4 ] . for the calculation of dvh parameters , two vital pieces of information are needed : dose information from the seed locations , and volume information using the boundaries of the prostate and surrounding critical structures . computed tomography ( ct ) is the current standard post - implant imaging modality , as the metallic radioactive seeds high atomic number and density result in high contrast between the seeds and prostatic tissue . however , the prostate is not well demarcated from surrounding tissues with similar densities , and combined with the seed streak artifacts that obscure prostate boundaries , prostate volumes can be overestimated on ct images [ 5 , 6 , 7 ] . high interobserver variation in prostate volume delineation on ct images [ 7 , 8 ] results in increased variability in post - implant dosimetry and obscures dose - response relationships . magnetic resonance imaging ( mri ) is an alternate post - implant imaging modality . currently , mri is the optimum imaging modality for staging of a suspected primary prostate malignancy . the primary advantage of mri compared to ct is that a variety of mri techniques allows for better anatomical visualization , such as intraprostatic detail , the prostate apex and base , internal pudendal artery , neurovascular bundles , penile bulb , bladder neck and urinary sphincters [ 6 , 7 , 10 , 11 , 12 , 13 ] . the low interobserver variation in prostate contouring on mri scans consistent and accurate quantitation of dose to critical structures , such as the urinary sphincter , would improve evaluation of dose - response relationships . the main drawback of using mri for post - implant dosimetry is that the seeds generally appear as hypointense signal voids that may be mistaken for needle tracks or blood vessels [ 14 , 15 ] . mri - ct fusion post - implant dosimetry allows for anatomical definition on mri images and seed localization on ct images . nonetheless , the mri - ct fusion quality is affected by registration quality ( registration landmarks , fusion technique , fusion algorithm parameters , personnel training and experience ) and imaging quality ( pulse sequence , contrast , pelvic tilt , coil , patient transit between scanners , duration between scans , bladder and rectal filling differences ) [ 16 , 17 , 18 , 19 ] . the advantages of mri - only post - implant dosimetry are superior soft tissue contrast , no extraneous radiation , imaging flexibility , and possible integration of functional imaging . however , mri is not as widely adopted as ct in prostate brachytherapy clinics owing to seed localization difficulties , image fusion issues , and logistical barriers . to assist in definitive seed localization on mri scans , frank et al . developed encapsulated contrast agent markers that can be placed in between seeds ( figure 1 ) . the markers do not affect dose distribution [ 20 , 21 ] , have minimal toxicity , and have well - defined mri relaxation properties [ 23 , 24 ] . b ) the appearance of markers ( hyperintense cylinders ) between seeds ( hypointense dumbbell - shaped voids ) in a commercially - available prostate phantom . the displayed sagittal slice was obtained at a plane crossing the center of the topmost marker . markers appear definitively as hyperintense regions , whereas signal voids may be seeds or needle tracks in this manuscript , we describe our experience in developing an appropriate mri protocol for marker visualization , and the process of incorporating the markers into our low dose rate ( ldr ) prostate brachytherapy clinical practice . in an institutional process quality improvement protocol , 10 prostate cancer patients selected to undergo ldr prostate brachytherapy were evaluated . various imaging modalities , such as transrectal ultrasound ( trus ) , ct , and mri were used throughout the implant workflow . these pre - implant images were used to generate the treatment plan on mim symphony ( cleveland , oh , usa ) , which has been previously commissioned . the markers ( sirius ; c4 imaging , houston , tx , usa ) contain cobalt dichloride - n - acetyl cysteine encapsulated in a polymer capsule of 5.5 mm length , 0.8 mm diameter , and have been approved by the united states food and drug administration for ldr prostate implants . the seed - marker strands were ordered directly from the seed manufacturer depending on the isotope ( isoray medical , richland , wa , usa ; isoaid , port richey , fl , usa ; theragenics , buford , ga , usa ) . after the implant , ct and mri scans were acquired on the day of implant and again approximately a month later . post - implant ct images were used to perform post - implant dosimetry for all patients according to the current standard of care . post - implant mri images were evaluated for marker , seed and prostatic anatomy visibility , as well as artifacts , including marker chemical shift , partial volume averaging , seed susceptibility , motion , and wraparound artifacts . the previous post - implant mri protocol consisted of three dimensional ( 3d ) t2-weighted fast spin echo ( fse ) , two dimensional ( 2d ) t2-weighted fse ( axial ) , and 2d t1-weighted fse ( axial / sagittal / coronal ) sequences . the 3d t2-weighted fse sequence ( ge : cube ; siemens : space , sampling perfection with application optimized contrasts using different flip angle evolution ) was routinely used for fusion with ct images . the updated post - implant mri protocol consists of a 3d fast radiofrequency - spoiled gradient - recalled echo ( fspgr ) sequence , with the scan parameters defined based on previous phantom studies   and repeat 3d fspgr scans performed to optimize the sequence for post - implant dosimetry ( table 1 ) . mri scans were acquired using a signa hdxt 3.0 t scanner ( ge , waukesha , wi , usa ) for eight patients , a signa hdxt 1.5 t scanner ( ge , waukesha , wi , usa ) for one patient , and a magnetom aera 1.5 t scanner ( siemens , malvern , pa , usa ) with the similar fast low angle shot ( flash ) sequence for one patient . except for the first patient , all patients were imaged with a disposable inflatable endorectal coil ( medrad ; bayer , whippany , nj , usa ) . surface coil intensity correction ( scic ) and phased array uniformity enhancement ( pure ) post - processing were applied to minimize the high signal intensity proximal to the endorectal coil . pulse sequence parameters for post - implant dosimetric assessment interpolated from 2 mm interpolated from 256  256 halved due to phase oversampling on the ct images ( figure 2 ) , the markers appeared isointense to the prostate tissue and were obscured by the seeds . on the other hand the seed positions were confounded by the metal streak artifacts and partial volume averaging artifacts , appearing longer and wider than the seeds physical dimensions . on the standard post - implant protocol 's 3d t2-weighted fse images ( figure 3 ) , the markers and seeds appeared inconsistently as hypointense cylinders or isointense to prostatic tissue . prostate anatomy was better visualized on the 3d t2-weighted fse images compared to ct images . axial ( a ) , sagittal ( b ) , and coronal ( c ) views of the prostate acquired using ct . seeds appeared hyperintense with streak artifacts axial ( a ) , sagittal ( b ) , and coronal ( c ) views of the prostate acquired using a 3d fast spin echo sequence . the hypointense seeds and markers were not clearly distinguishable on the updated protocol 's 3d fspgr images ( figure 4 ) , the markers appeared as hyperintense cylinders within the hypointense needles tracks , giving the characteristic appearance on axial images of bright filled circles with a dark outline . a chemical shift artifact of the marker was pronounced at low bandwidth ( bw ) . the marker chemical shift artifact results from slight differences between the larmor frequencies of hydrogen spins in the marker and the prostate , thereby displacing the marker in the frequency encoding direction . the bw should be high enough for minimal marker displacement but low enough for acceptable noise . to reduce partial volume averaging artifacts due to the small size of the markers , we used 0.27  0.27  1 mm voxels . the number of averages used was relatively high compared to standard sequences to increase the signal - to - noise ratio ( snr ) . axial ( a ) , sagittal ( b ) , and coronal ( c ) views of the prostate acquired using a 3d fast spoiled gradient echo sequence . markers appeared as hyperintense cylinders , while seeds appeared as hypointense dumbbell - shaped susceptibility voids on the other hand , the seeds appeared as hypointense dumbbell shapes , with wider widths at the ends of the seeds compared to the center of the seeds . these dumbbell shaped seed susceptibility artifacts were seen as the magnetic field inhomogeneity was distorted owing to the higher magnetic permeability of the seeds metallic casing , especially at the end - welding , compared to background prostatic tissue . the seed susceptibility artifact was more pronounced at low bw and more visible on 3d fspgr images compared to 3d fse images due to the lack of a 180 pulse that cancels out magnetic field inhomogeneities . the seed susceptibility artifact , along with the markers , enabled easier seed centroid identification . intraprostatic detail was not as clearly visualized with the 3d fspgr sequence ( figure 4 ) compared to the 3d t2-weighted fse sequence ( figure 3 ) . nevertheless , for post - implant dosimetry purposes , only prostate boundary delineation is needed . patient motion caused a ripple appearance in the phase encoding direction due to improper registration of phase information , which obscured prostate margins and impaired seed and marker identification ( figure 5 ) . the motion artifact could be expected owing to peristaltic or respiratory motion during the long ( > 10 minutes ) image acquisition . similar to diagnostic sequences , these motion artifacts should be directed away from the prostate by setting the phase encoding direction to right / left ( r / l ) . b ) phase - encoding direction = right / left the wraparound artifact could also be seen in the phase encoding direction owing to improper assignment of phase shift information and could affect marker visibility . to reduce this artifact , a common technique is to set the phase encoding direction to anterior / posterior because the anteroposterior width usually has the shortest skin - to - skin distance . however , since the imaging fov was smaller than the anteroposterior width of most patients , patient anatomy outside the fov would wrap into the image ( figure 6 ) . to reduce the wraparound artifact , we oversampled the fov , used saturation bands to reduce superimposed signal from outside the imaging fov , and kept the patient 's arms away from their sides . axial views of the prostate acquired using a 3d fspgr sequence with no wrap artifact ( a ) versus with wrap artifact ( b ) 
  minimizing the motion artifact and wraparound artifact required the phase - encoding to be set in different directions . nevertheless , using phase oversampling , the wraparound artifact would not extend into the prostate ; hence preventing the motion artifact from impinging into the prostate region could be prioritized to ensure visualization of the prostate boundaries and markers / seeds within the prostate for the purposes of post - implant dosimetric evaluation . therefore , the phase - encoding direction should be set to r / l . for patients with lateral widths greater than the oversampled fov , the wrap artifact would be observable ( hyperintense tissue visible on r / l edges of the axial view figure 4a and coronal view figure 4c ) . patients biomedical implants may be contraindicated for 3.0 t mri but may be allowed to be scanned at lower field strengths . a reduction in field strength corresponds to a reduction in power deposition in the patient , relaxation times , susceptibility artifact effect , snr , and geometric distortion . at 1.5 t , the image quality was reduced compared to 3.0 t images but the visibility of the markers was not compromised . endorectal coils are routinely used to enhance the prostate signal for diagnostic sequences , as the prostate is centered in the body while signal from the torso coil falls off away from the skin . identification of the seeds and markers was difficult without the endorectal coil ( figure 6a ) . however , endorectal coils may deform the prostate , resulting in mri - ct fusion difficulties and producing unnatural dose distributions . to reduce prostate deformation while maintaining coil immobility , the endorectal coil was slightly inflated to only 30 cc instead of maximum inflation . post - implant dosimetry improves care by allowing for corrective measures to be taken if necessary , and can improve the care of future patients through implant quality feedback to the brachytherapy team . communication of the methodology and end - points of post - implant dosimetric assessment by the brachytherapy team to the mri team is crucial to ensure useful images are acquired while maintaining high snr , minimal artifacts , and reasonable scan time . in this study , we described our experience in developing an mri protocol for marker and prostate visualization , and the incorporation of markers into our ldr prostate brachytherapy clinical practice . this is the first study presenting the appearance of mri markers in human prostate , and the first evaluation of the practical feasibility of using these markers as part of the ldr prostate brachytherapy workflow . our mri protocol consists of a 3d fspgr scan for marker visualization and an optional 3d t2-weighted fse scan for detailed anatomical visualization . the 3d fspgr scan may be used as the sole image set to identify markers and seeds , and provides adequate prostate edge visualization for contouring . however , mri - ct fusion can be done using either the 3d fspgr or 3d fse scans in our protocol for fusion with ct images , if desired . especially on the 3d fspgr images , the markers can be visualized , potentially allowing for greater registration to ct images , as the markers and seeds are interleaved . mri - mri fusion post - implant dosimetry can also be straightforwardly done with our protocol 's 3d fspgr and 3d fse scans , as these scans were acquired consecutively using an endorectal coil with the same scan prescription . a limitation of the study is that the effects of different scan parameters , scan conditions , and scanner manufacturers could not be comprehensively studied due to scanner time constraints , patient comfort concerns , and the small patient sample size . on the other hand , based on the imaging findings of this study , we are currently acquiring mri images of more patients implanted with markers to investigate if there is any clinically significant difference of dvh parameters between ct - only and mri - only post - implant dosimetry . the convenience of using the clinically - available spoiled gradient echo pulse sequence compared to novel pulse sequences for mri - based post - implant dosimetry was that the scan parameters could be matched with similar pulse sequences of different scanner manufacturers . the advantages of using markers for mri - based post - implant dosimetry are easier identification of hyperintense markers compared to hypointense seeds , prevention of spacers being incorrectly identified as seeds , and distinction between needle tracks and blood vessels . conversely , the limitations of mri - based post - implant dosimetry with markers include the indirect correspondence between hyperintense signals and seed positions , restriction to stranded use , difficult localization of migrated seeds , and manual marker - seed finding . however , compared to loose seeds , stranded seeds rarely migrate [ 26 , 27 ] . future work includes a semi - automated marker - seed finding algorithm to facilitate better integration of the markers into busy brachytherapy clinics . additionally , given the feasibility of incorporating markers into the ldr prostate brachytherapy clinic as presented in this study , more investigations are needed to evaluate the efficacy of marker - based mri - only post - implant dosimetry . the precision of dvh parameters generated from ct images , mri - ct fusion images , and mri images with the use of the markers could be compared . more importantly , the efficacy of these dvh parameters for the prediction of tumor control as well as acute and late effects of ldr prostate brachytherapy could be studied . furthermore , rigid endorectal coils with a smaller diameter compared to inflatable endorectal coils may be investigated to reduce prostate deformation while maintaining marker conspicuity . another potential future investigation is the incorporation of functional imaging sequences into the mri protocol for early prediction of treatment response . barriers to the adoption of mri for post - implant dosimetry are seed localization , time , cost , imaging complexity , and personnel education . we have illustrated an mri protocol for visualization of markers that may help overcome the barrier of seed localization and spur the use of mri for post - implant dosimetry . mri - based post - implant dosimetry may reduce inconsistencies in target delineation and subsequent reporting of dvh parameters . with more accurate dvh parameters , the dose - response relationship for critical organs and subsequent toxicity can be studied in a more meaningful manner , such that we can better manage the dose delivered to the prostate and surrounding critical structures in the future . steven j. frank is a cofounder of c4 imaging , llc , manufacturer of the mri markers .
purposecomputed tomography ( ct)-based prostate post - implant dosimetry allows for definitive seed localization but is associated with high interobserver variation in prostate contouring . currently , magnetic resonance imaging ( mri)-based post - implant dosimetry allows for accurate anatomical delineation but is limited due to inconsistent seed localization . encapsulated contrast agent markers were previously proposed to overcome the seed localization limitation on mri images by placing hyperintense markers adjacent to hypointense seeds . 
 the aim of this study was to assess the appearance of these markers in prostatic tissue , and develop an mri protocol to enable marker visualization.material and methodswe acquired mri scans in prostate implant patients ( n = 10 ) on day 0 ( day of implant ) and day 30 ( month after implant ) . before implantation of the markers , 
 the routine post - implant mri protocol included a 3d t2-weighted fast - spin - echo ( fse ) sequence with which markers and seeds could not be clearly visualized . to visualize the mri markers , a 3d fast radiofrequency - spoiled gradient - recalled echo ( fspgr ) sequence 
 was evaluated for marker and seed visibility , as well as prostate boundary definitions.resultsthe 3d fspgr sequence allowed for the visualization of markers in the prostate , enabling the distinction of signal voids as seeds versus needle tracks . 
 the updated post - implant mri protocol consists of this 3d fspgr scan and an optional 3d t2-weighted fse scan . 
 the optional 3d t2-weighted fse sequence may be employed to better visualize intraprostatic detail . 
 we also described the observed image artifacts , including seed susceptibility , marker chemical shift , partial volume averaging , motion , and wraparound artifacts.conclusionswe have demonstrated an mri protocol for use with hyperintense encapsulated contrast agent markers to assist in the identification of hypointense seeds .