prior to the development of ct angiography , planar ventilation / perfusion scans were the primary noninvasive method for diagnosis of pulmonary embolism ( pe ) . however , the technique suffered disrepute since the pioped i study showed that 65% of scans were nondiagnostic . as will be reviewed below , results from later studies based upon modern imaging techniques and new holistic principles ( combining clinical information , pretest probability , results of chest radiograph , and patterns typical of pe or other diseases ) reduce the number of nondiagnostic findings to 3% or less , while sensitivity and specificity are excellent [ 2 , 3 ] .   since the early 1980s , the advantage of tomography over planar imaging for pe detection was indicated . since then , numerous studies have shown such advantages of ventilation / perfusion single photon emission computed tomography ( v / pspect ) over alternative techniques , which indicated that lung scintigraphy is again appreciated as a first line method for diagnosis of pe . an important issue is to estimate the clinical probability for pe before performing imaging tests as is elaborated upon in the european guidelines for lung scintigraphy   and by mamlouk et al . . the object of this paper is to show the advantages of v / pspect in accordance with the european guidelines for v / pspect [ 2 , 3 ] . it will be emphasized that v / pspect gives diagnostic information in other conditions such as pneumonia , copd , and left heart failure . the presentation will focus on basic requirements on diagnostic methods for pe : no contraindications , high diagnostic accuracy and few nondiagnostic reports , utility for selection of treatment strategy , suitability for followup and research . the only gas that is useful for v / pspect is krypton , kr . its short half life ( 13  s ) implies that it disappears from the alveoli by decay rather than by exhalation . after some minutes of test gas breathing , when the alveolar concentration has approached a steady state reflecting alveolar ventilation , v / pspect is performed . the rubidium generator that delivers kr has a half life of 4.6  h. limited availability and high costs inhalation of a radio - aerosol is used in nearly all centers for ventilation scintigraphy . particles larger than 2  m are deposited in large airways ( hot spots ) . high flow rates at forced breathing patterns and turbulent flow enhance particle deposition in airways and augment tendencies to hot spots in ventilation images , particularly in chronic obstructive pulmonary disease ( copd ) . the mass median aerodynamic diameter , mmad , reflects radioactivity carried by each liquid particle . half of the radioactivity resides in particles smaller than mmad and 50% in larger ones . it is often recommended that the maximum droplet size inhaled by the patient should not exceed 2  m . because of the complex physics behind aerosol deposition pattern , the performance of a nebuliser must be clinically tested . diethylenetriaminepentaacetic acid labelled with technetium , tc - dtpa , is in general use for ventilation scintigraphy with liquid aerosols . the size of the water solvable molecule is 492 dalton . therefore , tc - dtpa diffuses through the alveolocapillary membrane to the blood . in a healthy patient , increased clearance , leading to a shorter half life is observed with alveolar inflammation of any kind , such as alveolitis of allergic or toxic nature and even in smokers [ 79 ] . technegas is an aerosol of extremely small carbon particles , 0.0050.2  m , generated in a high temperature furnace [ 1012 ] . the small particle size implies that they are distributed in the lungs almost like a gas and are deposited in alveoli by diffusion [ 13 , 14 ] . recently , a head to head study of deposition patterns using technegas and tc - dtpa performed in a group of patients routinely admitted for v / pspect and in a group of patients with known copd was published . unevenness of radiotracer deposition and degree of central deposition were less with technegas , particularly in the obstructive patients , figure 1 . in some patients , mismatched perfusion defects were only identified using technegas because the marked peripheral unevenness of tc - dtpa obscured mismatch and thereafter pe might have been overlooked in copd patients using tc - dtpa . in a few patients , it was concluded that technegas is the superior radio - aerosol , particularly in patients with obstructive lung disease . another advantage of using technegas is that a few breaths are sufficient to achieve an adequate amount of activity in the lungs . for perfusion scintigraphy , radio - labelled maa , sized 15100  m , is injected intravenously . this causes microembolization of pulmonary capillaries and precapillary arterioles , reflecting regional perfusion if at least 60  000 particles are injected . as there are over 280 billion pulmonary capillaries and 300 million precapillary arterioles , only a small fraction of the pulmonary bed will be obstructed . fewer particles might be used in patients with known pulmonary hypertension or after single lung transplantation . using a dual head camera , palmer et al . developed a fast and efficient clinical method for v / pspect . a new algorithm allows calculation of the quotient between ventilation and perfusion and presentation of v / pquotient images for easier diagnosis and quantification of pe extension . the ventilation study starts with inhalation of 2530  mbq tc - dtpa or technegas . immediately after ventilation spect , a dose of 100120  mbq tc maa is given intravenously for perfusion imaging . during the examination the doses of 30  mbq and 120  mbq for ventilation and perfusion , respectively , allow excellent v / pspect quality at an effective radiation dose of 1.8  msv . iterative reconstruction is performed using ordered subset expectation maximization ( osem ) , for example , with 8 subsets and 2 iterations . in processing the images , the ventilation background was subtracted from the perfusion tomograms and a normalized v / p image set calculated , v / pquotient . the algorithms for v / pquotient were developed by palmer et al . and further amended by bajc et al . the main consideration in the creation of  v / pquotient images was to scale smoothened ventilation and perfusion data sets to display v / pquotient in a fixed linear scale allowing separation of normal regions from those with mismatch ( figure 2 ) . the basic format for v / pspect presentation is displayed slices in frontal , sagittal , and transversal projections , available on any modern system . the slices must be accurately aligned so that ventilation and perfusion slices match each other and can be correctly compared . it is of value to achieve this acquisition in one session with maintained body position . this is also a prerequisite for the calculation of v / pquotient images , which greatly facilitates identification and quantification of pe . volume rendered images , such as  maximum intensity projection  , are available with almost all spect systems , allowing rotating 3d views . such displays might be useful , particularly for quantification and followup of pe patients . using a porcine model based upon tl - marked emboli as a  gold standard  , bajc et al . validated the new v / pspect method for diagnosis of pe and confirmed the superior value of tomography over planar imaging and improved interobserver agreement of defects on the subsegmental level . in a following clinical head to head comparison between planar imaging and v / pspect , it was shown that 53% more mismatch points were identified with v / pspect compared to the planar technique . spect eliminates superimposed structures , clarifying the segmental and sub - segmental nature of perfusion defect caused by pe . lung scintigraphy for diagnosis of pe and other diseases should routinely include ventilation and perfusion studies [ 21 , 23 , 25 , 27 , 29 ] . in pe , a perfusion defect is due to an embolus blocking blood flow . because there is no corresponding blockage in the airway , perfusion defects due to blockage of a pulmonary artery should reflect the branching of pulmonary circulation and its classical segmental anatomy . a segmental defect is wedge shaped and with its base on the pleura as will be illustrated ( figure 3 ) . the european guidelines [ 2 , 3 ] advocate the new holistic interpretation and reporting of lung spect . argued that  the expert 's successful interpretation of lung scans exceeds the best accuracy achievable by algorithms , which , by definition , are distillations of decision making into finite linear steps . the subjective of the whole is superior to any possible attempt to define its discrete parts  . a holistic interpretation of v / pspect images includes ( 1 ) clinical information and pretest probability for pe , ( 2 ) chest x - ray when available , ( 3 ) recognition of patterns typical for pe based upon segmental charts , and ( 4 ) recognition of patterns of other diseases than pe whenever possible [ 21 , 23 ] . the clinician can only benefit from reports , which clearly express the presence or absence of pe . this goal was not reached with previous probabilistic reporting methods according to pioped or modified pioped , which defied how planar scans are reported [ 1 , 31 ] . large v / pspect studies show that this is achievable if all patterns representing ventilation together with perfusion are considered [ 23 , 3234 ] . recommended criteria for reading v / pspect with respect to acute pe described in the european guidelines are as follows . no pe is reported if there are any of the following features : normal perfusion pattern conforming to the anatomic boundaries of the lungs ,   matched or reversed mismatch v / p defects of any size , shape , or number in the absence of mismatch ,   mismatch that does not have a lobar , segmental or subsegmental pattern . pe is reported if there is v / p mismatch of at least one segment or two subsegments that conforms to the pulmonary vascular anatomy . nondiagnostic for pe is reported if there are multiple v / p abnormalities not typical of specific diseases .  
				 in pe , it is fundamental that mismatched areas are conical with the base of the cone along the pleura and conform to known sub - segmental and segmental vascular anatomy . with such interpretation criteria , recent v / pspect studies in over 3000 cases showed according to a recent review a negative predictive value of 9799% , a sensitivity of 9699% , and a specificity of 9198% for pe . using our technique , v / pspect yields ventilation and perfusion images in exactly the same projections . this makes calculation of v / pquotient images possible and facilitates recognition of mismatch , particularly important in the middle lobe and lingula where mismatch may be overlooked if the lung is not accurately delineated by its ventilation images . v / pspect is the method of choice for quantification of the extent of embolism , because all emboli in the whole lung are recognised and it has greater sensitivity compared to mdct [ 27 , 32 , 33 ] . the number of segments and sub - segments indicating for pe typical mismatch are counted and expressed in % of the total lung parenchyma . a segmental reduction or a sub - segmental total deficiency of function therefore , the 9 segments of each lung can be represented by the total of 18 points . mismatch defects are expressed as mismatch points , which after division by 36 give the fraction of the lung that is embolized . the reduction in total overall lung function can be estimated by adding the number of regions with reduced ventilation and/or perfusion . patients with up 40% pe could be safely treated at home if ventilation abnormalities engaged not more that 20% of the lung . since 2004 , the university hospital of lund has safely treated about 60% of patients with pe at home ( approximately 1500 ) . v / pspect images allow clear identification of segmental and sub - segmental perfusion defects , as in figure 2 from a woman with extensive pe .  
 figure 3 shows a well - delineated segmental perfusion defect . followup after three days showed an almost normal pattern , confirming the diagnosis of pe . such findings are often observed in patients with heart failure , mediastinal adenopathy , postradiation therapy , and so forth . the clinical value of v / pspect has been confirmed in several studies [ 27 , 29 , 3234 ] . in a recent review . v / pspect is today the method recommended by the european association of nuclear medicine for clinical diagnosis , followup , and research . management of pe was previously confined to in - hospital therapy , using thrombolysis or heparin injections followed by oral anticoagulants for extended periods of time . it has been shown that out - patient treatment is safe when based upon v / pspect that quantifies pe extension and identifies v / p defects of other etiologies . v / pspect is accordingly a tool to guide the individual treatment . for followup , v / pspect is the method recommended by the european association of nuclear medicine due to its high sensitivity , noninvasiveness , low radiation exposure , and absence of contraindications . clinical reasons for followup are persistent v / p mismatches often occur after pe ; pe may recur in identical locations ; a prior study will help determine the age of a new defect ; 
								 there is an impact on therapy decision . obviously , evaluation of different drugs and treatment strategies merits the use of v / pspect because of its high sensitivity and quality with regards to quantification . v / pspect allows diagnosis of several other diseases which have different scintigraphic appearances to pe , as detailed below [ 2 , 3 , 37 ] . in ventilation defects are commonly more prominent than those of perfusion which leads to a pattern called reverse mismatch . notably , v / pspect allows the diagnosis of pe even in the presence of copd [ 32 , 37 ] , figure 4 . in left heart failure , ventilation is usually not affected to the same degree as perfusion , which leads to a mismatch pattern . importantly , this pattern does not conform to segmental anatomy of pulmonary arteries and it is not of a segmental character . among patients referred for suspected pe , the most frequent finding is a matched defect . in case of partly preserved perfusion , reversed mismatch is observed [ 40 , 41 ] . preserved perfusion along the pleural border leads to a  stripe sign  [ 42 , 43 ] . v / pspect frequently shows this sign because no overlaying structures obscure the images , figure 6 . suspicion or knowledge that a patient has pneumonia does not contraindicate v / pspect . on the contrary , the qualities of v / pspect rely upon adequate and standardized technology of combined ventilation and perfusion studies as well as new holistic interpretation criteria as discussed . furthermore , it allows quantification of pe that in some centres has impact on choice of treatment . its outstanding qualities merit consideration of its use as the primary diagnostic method for pe in all hospitals in which nuclear medicine is practiced . v / pspect frequently gives diagnosis of both pe as well as comorbid conditions as copd , left heart failure , and pneumonia .
v / pspect has the potential to become a first hand tool for diagnosis of pulmonary embolism based on standardized technology and new holistic interpretation criteria . 
 pretest 
 probability helps clinicians choose the most appropriate objective test for diagnosis or exclusion of pe . 
 interpretation should also take into account all ventilation and perfusion patterns allowing diagnosis of other cardiopulmonary diseases than pe . 
 in such contexts , v / pspect has excellent sensitivity and specificity . 
 nondiagnostic reports are 3% . 
 v / pspect has no contraindication ; it is noninvasive and has very low radiation exposure . 
 moreover , acquisition time for v / pspect is only 20 minutes . 
 it allows quantification of pe extension which has an impact on individual treatment . 
 it is uniquely useful for followup and research .