assessment of myocardial viability in patients with coronary artery disease is of great clinical importance , as dysfunctional but viable myocardium has the ability to regain contractility after coronary revascularization with subsequent improvements in cardiac function and prognosis . the perfusable tissue index ( pti )
can be used as a marker of myocardial viability , having been validated in patients with ischaemic heart disease [ 27 ] .
however , pti has never been used in clinical practice , primarily due to the complex imaging protocol consisting of dynamic [ o]h2o and [ o]co scans , together with a transmission scan , and the lack of high - quality , clinically usable parametric images .
recently , however , a method was developed to derive the pti from a single [ o]h2o pet / ct scan .
given the current potential of clinical [ o]h2o - based perfusion imaging and the rapid growth in the availability of cardiac pet / ct systems , pti viability measurements could become incorporated into clinical practice [ 9 , 10 ] .
parametric pti images derived from [ o]h2o pet / ct scans , however , have not yet been validated .
the purpose of this study was to compare these novel parametric pti images with late gadolinium - enhanced cardiovascular magnetic resonance ( lge - cmr ) imaging , an established method for quantifying scar size and a marker of viability .
the study population comprised 46 patients with documented or suspected coronary artery disease who had been studied using both pet / ct and cmr within a 2-month period .
all patients were in a stable clinical condition and no ischaemic events or revascularizations had occurred during the period between the two examinations .
patients with contraindications for pet / ct or cmr ( e.g. pacemaker , claustrophobia , atrial fibrillation ) were excluded .
the study was approved by the institutional medical ethics review committee , and all participants gave written informed consent prior to inclusion .
[ o]h2o scans were acquired using a gemini tf-64 ( philips healthcare , best , the netherlands ) pet / ct scanner .
[ o]h2o ( 370  mbq ) was injected as a 5-ml bolus ( 0.8  ml  s ) followed by a 35-ml saline flush ( 2  ml  s ) , simultaneously starting a 6-min list mode emission scan .
this scan was followed immediately by a respiration - averaged slow low - dose ( ld ) ct scan ( 55 mas , rotation time 1.5  s , pitch 0.825 , collimation 16    0.625 , acquiring 20  cm in 37  s ) during normal breathing .
all scans were checked for misalignment between the ld ct scan and the [ o]h2o scan ; in none of the patients were corrections needed .
dynamic [ o]h2o images were reconstructed into 22 frames ( 1    10 , 8    5 , 4    10 , 2    15 , 3    20 , 2    30 , 2    60  s ) using the three - dimensional row action maximum likelihood algorithm and applying all appropriate corrections for the scanner , normalization , dead time , decay , scatter , randoms and attenuation based on the corresponding ld ct scan . using capp software ( siemens / cti , knoxville , tn ) , regions of interest ( rois ) of 1  cm diameter were placed over the ascending aorta in at least ten transaxial image planes of the frame showing the first pass of the injected bolus .
these rois were combined into one volume of interest ( voi ) for the ascending aorta .
a second set of rois were placed over the right ventricle ( rv ) cavity in at least five transaxial planes , with roi boundaries at least 1  cm from the rv wall to avoid spill - in from myocardial activity .
both vois were then projected onto all dynamic [ o]h2o images , thereby generating arterial ( ca(t ) ) and rv ( crv(t ) ) time  activity curves .
parametric pti images were calculated as previously described . in brief , parametric images of myocardial blood flow ( mbf ) , perfusable tissue fraction ( ptf ) , and arterial and venous blood volume fractions were calculated using a basis function implementation of the standard single - tissue compartment model for [ o]h2o [ 1114 ] .
parametric images of arterial and venous blood volume fractions were subtracted from normalized ct transmission images , resulting in parametric anatomic tissue fraction ( atf ) images . finally , parametric pti images were calculated as the ratio of ptf and atf images ( fig .  1 ) .
finally , 16 myocardial vois were defined manually on parametric ptf images , according to the 16 segments model of the american heart association , after which this voi template was projected onto the parametric pti images.fig .
( b ) atf ( g  ml ) , ( c ) ptf ( g  ml ) , and ( d ) pti in a patient without coronary artery disease example of short axis images of ( a ) blood volume , ( b ) atf ( g  ml ) , ( c ) ptf ( g  ml ) , and ( d ) pti in a patient without coronary artery disease cmr studies were performed on a 1.5-t whole - body scanner ( magnetom sonata or avanto ; siemens , erlangen , germany ) , using a six - channel phased - array body coil . after survey scans ,
a retrotriggered , balanced steady - state free precession gradient - echo sequence was used for cine imaging .
image parameters included : slice thickness 5  mm , slice gap 5  mm , temporal resolution < 50  ms , repetition time 3.2  ms , echo time 1.54  ms , flip angle 60 , typical image resolution 1.3    1.6    5.0  mm .
the cardiac cycle consisted of 20 phases . after obtaining four- , three- and two - chamber view cines ,
stacks of 10 to 12 short - axis slices were acquired to fully cover the left ventricle ( lv ) .
contrast images were acquired 10 to 15  min after administration of 0.2  mmol  kg gadolinium - dtpa in the same views as in the cine images , using a two - dimensional segmented inversion - recovery prepared gradient echo sequence ( te 4.4  ms , tr 9.8  ms , inversion time 250 to 300  ms , typical voxel size 1.3    1.6    5.0  mm ) .
images were analysed off - line using the software package mass ( mr analytical software system ; medis , leiden , the netherlands ) .
the endocardial and epicardial borders of the lv were outlined manually in both end - diastolic and end - systolic phases of all short - axis images .
end - diastolic volume , end - systolic volume and ejection fraction were computed using these analyses .
the amount of fibrosis was calculated using the full - width at half - maximum method , which defines fibrosis as myocardial tissue with a signal intensity 50  % of the maximum hyperenhancement intensity . if no enhancement was found in a slice , the maximum signal of the nearest slice with enhancement was used .
all areas of enhancement were quantified by computer - assisted planimetry on each of the short - axis images and the segmental extent of enhancement was expressed as a percentage of the segmental area .
cmr images were analysed according to the same 16-segment model as used for the parametric pet images .
finally , myocardial segments were graded as viable or nonviable using the previously defined cut - off value of 50  % lge per segment [ 15 , 17 ] .
continuous variables are presented as means  sd , and categorical data are summarized as frequencies and percentages .
multiple datasets were compared using analysis of variance ( anova ) , and specific differences were identified using student s t - test with bonferroni inequality adjustment .
receiver operating characteristic curves were generated for ptf , pti and mbf for the prediction of myocardial viability assessed by lge cmr .
the area under the curve ( auc ) was considered a measure of accuracy to discriminate between viable and nonviable myocardium .
the study population comprised 46 patients with documented or suspected coronary artery disease who had been studied using both pet / ct and cmr within a 2-month period .
all patients were in a stable clinical condition and no ischaemic events or revascularizations had occurred during the period between the two examinations .
patients with contraindications for pet / ct or cmr ( e.g. pacemaker , claustrophobia , atrial fibrillation ) were excluded .
the study was approved by the institutional medical ethics review committee , and all participants gave written informed consent prior to inclusion .
[ o]h2o scans were acquired using a gemini tf-64 ( philips healthcare , best , the netherlands ) pet / ct scanner .
[ o]h2o ( 370  mbq ) was injected as a 5-ml bolus ( 0.8  ml  s ) followed by a 35-ml saline flush ( 2  ml  s ) , simultaneously starting a 6-min list mode emission scan .
this scan was followed immediately by a respiration - averaged slow low - dose ( ld ) ct scan ( 55 mas , rotation time 1.5  s , pitch 0.825 , collimation 16    0.625 , acquiring 20  cm in 37  s ) during normal breathing .
all scans were checked for misalignment between the ld ct scan and the [ o]h2o scan ; in none of the patients were corrections needed .
dynamic [ o]h2o images were reconstructed into 22 frames ( 1    10 , 8    5 , 4    10 , 2    15 , 3    20 , 2    30 , 2    60  s ) using the three - dimensional row action maximum likelihood algorithm and applying all appropriate corrections for the scanner , normalization , dead time , decay , scatter , randoms and attenuation based on the corresponding ld ct scan . using capp software ( siemens / cti , knoxville , tn ) , regions of interest ( rois ) of 1  cm diameter were placed over the ascending aorta in at least ten transaxial image planes of the frame showing the first pass of the injected bolus .
these rois were combined into one volume of interest ( voi ) for the ascending aorta .
a second set of rois were placed over the right ventricle ( rv ) cavity in at least five transaxial planes , with roi boundaries at least 1  cm from the rv wall to avoid spill - in from myocardial activity .
both vois were then projected onto all dynamic [ o]h2o images , thereby generating arterial ( ca(t ) ) and rv ( crv(t ) ) time  activity curves .
parametric pti images were calculated as previously described . in brief , parametric images of myocardial blood flow ( mbf ) , perfusable tissue fraction ( ptf ) , and arterial and venous blood volume fractions were calculated using a basis function implementation of the standard single - tissue compartment model for [ o]h2o [ 1114 ] .
parametric images of arterial and venous blood volume fractions were subtracted from normalized ct transmission images , resulting in parametric anatomic tissue fraction ( atf ) images . finally , parametric pti images were calculated as the ratio of ptf and atf images ( fig .  1 ) .
finally , 16 myocardial vois were defined manually on parametric ptf images , according to the 16 segments model of the american heart association , after which this voi template was projected onto the parametric pti images.fig .
( b ) atf ( g  ml ) , ( c ) ptf ( g  ml ) , and ( d ) pti in a patient without coronary artery disease example of short axis images of ( a ) blood volume , ( b ) atf ( g  ml ) , ( c ) ptf ( g  ml ) , and ( d ) pti in a patient without coronary artery disease
cmr studies were performed on a 1.5-t whole - body scanner ( magnetom sonata or avanto ; siemens , erlangen , germany ) , using a six - channel phased - array body coil . after survey scans ,
a retrotriggered , balanced steady - state free precession gradient - echo sequence was used for cine imaging .
image parameters included : slice thickness 5  mm , slice gap 5  mm , temporal resolution < 50  ms , repetition time 3.2  ms , echo time 1.54  ms , flip angle 60 , typical image resolution 1.3    1.6    5.0  mm .
the cardiac cycle consisted of 20 phases . after obtaining four- , three- and two - chamber view cines ,
stacks of 10 to 12 short - axis slices were acquired to fully cover the left ventricle ( lv ) .
contrast images were acquired 10 to 15  min after administration of 0.2  mmol  kg gadolinium - dtpa in the same views as in the cine images , using a two - dimensional segmented inversion - recovery prepared gradient echo sequence ( te 4.4  ms , tr 9.8  ms , inversion time 250 to 300  ms , typical voxel size 1.3    1.6    5.0  mm ) .
images were analysed off - line using the software package mass ( mr analytical software system ; medis , leiden , the netherlands ) .
the endocardial and epicardial borders of the lv were outlined manually in both end - diastolic and end - systolic phases of all short - axis images .
end - diastolic volume , end - systolic volume and ejection fraction were computed using these analyses .
the amount of fibrosis was calculated using the full - width at half - maximum method , which defines fibrosis as myocardial tissue with a signal intensity 50  % of the maximum hyperenhancement intensity .
if no enhancement was found in a slice , the maximum signal of the nearest slice with enhancement was used .
all areas of enhancement were quantified by computer - assisted planimetry on each of the short - axis images and the segmental extent of enhancement was expressed as a percentage of the segmental area .
cmr images were analysed according to the same 16-segment model as used for the parametric pet images .
finally , myocardial segments were graded as viable or nonviable using the previously defined cut - off value of 50  % lge per segment [ 15 , 17 ] .
continuous variables are presented as means  sd , and categorical data are summarized as frequencies and percentages .
multiple datasets were compared using analysis of variance ( anova ) , and specific differences were identified using student s t - test with bonferroni inequality adjustment .
receiver operating characteristic curves were generated for ptf , pti and mbf for the prediction of myocardial viability assessed by lge cmr .
the area under the curve ( auc ) was considered a measure of accuracy to discriminate between viable and nonviable myocardium . a p value of < 0.05 was considered statistically significant .
lge was seen in the cmr images of 34 patients ( 74  % ) . of the 736 myocardial segments ,
364 ( 49  % ) showed some degree of lge.table 1patient characteristics ( n  =  46)characteristicvalueage ( years)65    10gender ( male)36 ( 78  % ) previous myocardial infarction34 ( 74  % ) lv end - diastolic volume ( ml)226    65lv end - systolic volume ( ml)135    71lv ejection fraction ( % ) 42    16lv mass ( g)132    39 patient characteristics ( n  =  46 ) pet / ct and cmr data are summarized in table  2 . there was a gradual decrease in ptf , pti and mbf values with increasing degree of lge on cmr images ( p  <  0.001 by anova ) .
atf values remained relatively constant , except for a significant decrease in the ( near ) transmurally enhanced segments ( p  <  0.001 by anova).table 2segmental pet / ct and lge dataextent of lge ( % ) control
( n  =  372)025 ( n  =  190)2550 ( n  =  83)5075 ( n  =  54)75 ( n  =  37)p value ( anova)atf0.76    0.090.77    0.090.75    0.110.73    0.080.68    0.11**<0.001ptf ( g  ml)0.72    0.080.72    0.090.70    0.090.60    0.08**0.51    0.12***<0.001pti0.91    0.080.89    0.090.89    0.090.77    0.10**0.70 
  0.16***<0.001mbf ( ml  g  min)1.02    0.300.91    0.26 * 0.85    0.30 * 0.83    0.24 * 0.67    0.30**<0.001*p  <  0.05 vs. control ; * * p  <  0.05 vs. control , 025  % lge and 2550  % lge ; * * * p  <  0.05 vs. control , 025  % lge , 2550  % lge and 5075  % lge . segmental pet / ct and lge data * p  <  0.05 vs. control ; * * p  <  0.05 vs. control , 025  % lge and 2550  % lge ; * * * p  <  0.05 vs. control , 025  % lge , 2550  % lge and 5075  % lge .
figure  2 shows a concordant pattern between parametric ptf , pti and lge cmr images in a patient with ischaemic cardiomyopathy after an anterior myocardial infarction.fig .
2long axis images ( a  d ) and polar maps ( e  h ) in a patient with an anterior myocardial infarction : a , e cmr with lge ( arrow , % transmurality ) ; b , f ptf ( g  ml ) ; c , g pti ; d , h mbf ( ml  g  min)fig .
3long axis images in a patient with a nontransmural anterior myocardial infarction : a cmr with lge ; b pti long axis images ( a  d ) and polar maps ( e  h ) in a patient with an anterior myocardial infarction : a , e cmr with lge ( arrow , % transmurality ) ; b , f ptf ( g  ml ) ; c , g pti ; d , h mbf ( ml  g  min ) long axis images in a patient with a nontransmural anterior myocardial infarction : a cmr with lge ; b pti using cmr as a reference , 91 of 364 ( 25  % ) segments showing some degree of lge were judged to be nonviable ( lge > 50  % ) . as shown in fig .  4 ,
the values of ptf and pti for predicting myocardial viability in all 736 segments were comparable ( auc 0.87 , ci 0.830.90 , and 0.86 , ci 0.820.91 , respectively , p  =  0.541 ) .
mbf was able to predict myocardial viability with less accurate ( auc 0.69 , ci 0.630.75 , p  <  0.001 ) .
optimal cut - off values of ptf , pti and mbf for predicting ( near ) transmural lge on cmr were 0.69  g  ml , 0.80 , and 0.78  ml  min  g with sensitivities of 69  % , 91  % and 72  % , and specificities of 87  % , 73  % and 56  % , respectively .
figure  3 shows an example of a patient with a nontransmural scar and a corresponding relatively high pti.fig .
4receiver operator characteristics curves for the abilities of ptf , pti and mbf to differentiate between viable and nonviable segments based on late gadolinium enhancement receiver operator characteristics curves for the abilities of ptf , pti and mbf to differentiate between viable and nonviable segments based on late gadolinium enhancement
lge was seen in the cmr images of 34 patients ( 74  % ) . of the 736 myocardial segments ,
364 ( 49  % ) showed some degree of lge.table 1patient characteristics ( n  =  46)characteristicvalueage ( years)65    10gender ( male)36 ( 78  % ) previous myocardial infarction34 ( 74  % ) lv end - diastolic volume ( ml)226    65lv end - systolic volume ( ml)135    71lv ejection fraction ( % ) 42    16lv mass ( g)132    39 patient characteristics ( n  =  46 )
pet / ct and cmr data are summarized in table  2 . there was a gradual decrease in ptf , pti and mbf values with increasing degree of lge on cmr images ( p  <  0.001 by anova ) .
atf values remained relatively constant , except for a significant decrease in the ( near ) transmurally enhanced segments ( p  <  0.001 by anova).table 2segmental pet / ct and lge dataextent of lge ( % ) control
( n  =  372)025 ( n  =  190)2550 ( n  =  83)5075 ( n  =  54)75 ( n  =  37)p value ( anova)atf0.76    0.090.77    0.090.75    0.110.73    0.080.68    0.11**<0.001ptf ( g  ml)0.72    0.080.72    0.090.70    0.090.60    0.08**0.51    0.12***<0.001pti0.91    0.080.89    0.090.89    0.090.77    0.10**0.70    0.16***<0.001mbf ( ml  g  min)1.02    0.300.91    0.26 * 0.85    0.30 * 0.83    0.24 * 0.67    0.30**<0.001*p  <  0.05 vs. control ; * * p  <  0.05 vs. control , 025  % lge and 2550  % lge ; * * * p  <  0.05 vs. control , 025  % lge , 2550  % lge and 5075  % lge .
segmental pet / ct and lge data * p  <  0.05 vs. control ; * * p  <  0.05 vs. control , 025  % lge and 2550  % lge ; * * * p  <  0.05 vs. control , 025  % lge , 2550  % lge and 5075  % lge .
figure  2 shows a concordant pattern between parametric ptf , pti and lge cmr images in a patient with ischaemic cardiomyopathy after an anterior myocardial infarction.fig .
2long axis images ( a  d ) and polar maps ( e  h ) in a patient with an anterior myocardial infarction : a , e cmr with lge ( arrow , % transmurality ) ; b , f ptf ( g  ml ) ; c , g pti ; d , h mbf ( ml  g  min)fig .
3long axis images in a patient with a nontransmural anterior myocardial infarction : a cmr with lge ; b pti long axis images ( a  d ) and polar maps ( e  h ) in a patient with an anterior myocardial infarction : a , e cmr with lge ( arrow , % transmurality ) ; b , f ptf ( g  ml ) ; c , g pti ; d , h mbf ( ml  g  min ) long axis images in a patient with a nontransmural anterior myocardial infarction : a cmr with lge ; b pti using cmr as a reference , 91 of 364 ( 25  % ) segments showing some degree of lge were judged to be nonviable ( lge > 50  % ) . as shown in fig .  4 ,
the values of ptf and pti for predicting myocardial viability in all 736 segments were comparable ( auc 0.87 , ci 0.830.90 , and 0.86 , ci 0.820.91 , respectively , p  =  0.541 ) .
mbf was able to predict myocardial viability with less accurate ( auc 0.69 , ci 0.630.75 , p  <  0.001 ) .
optimal cut - off values of ptf , pti and mbf for predicting ( near ) transmural lge on cmr were 0.69  g  ml , 0.80 , and 0.78  ml  min  g with sensitivities of 69  % , 91  % and 72  % , and specificities of 87  % , 73  % and 56  % , respectively .
figure  3 shows an example of a patient with a nontransmural scar and a corresponding relatively high pti.fig .
4receiver operator characteristics curves for the abilities of ptf , pti and mbf to differentiate between viable and nonviable segments based on late gadolinium enhancement receiver operator characteristics curves for the abilities of ptf , pti and mbf to differentiate between viable and nonviable segments based on late gadolinium enhancement
the present study was conducted to validate the use of a parametric myocardial viability imaging technique using [ o]h2o pet / ct in patients with ischaemic heart disease .
viability assessed using parametric ptf and pti imaging was in good agreement with that assessed using lge cmr .
furthermore , these images and myocardial perfusion imaging are obtained simultaneously allowing both myocardial viability and ischaemia to be evaluated in a single scanning session .
[ o]h2o is generally considered to be the gold standard for absolute quantification of myocardial perfusion in vivo [ 10 , 18 , 19 ] .
apart from mbf , [ o]h2o also provides estimates of the extent of myocardium within a roi that is able to exchange water rapidly , i.e. ptf .
subsequently , ptf can be corrected for partial volume effects by dividing it by its anatomical counterpart atf , resulting in pti .
it has been shown that both ptf and pti can identify myocardial scarring and thus can act as markers of viability . only recently ,
however , a method has been developed that enables generation parametric atf , ptf and pti images from a single [ o]h2o pet / ct scan .
in addition , the traditional ( long ) transmission scan can be replaced by a ( rapid ) low - dose ct scan , thereby shortening the total scanning time substantially .
now that the method has been shown to produce high - quality parametric images , its implementation into clinical practice needs investigation . using the described parametric imaging approach
, the present study demonstrated that atf was relatively constant independent of tissue characteristics of the myocardium . only in ( near )
transmurally infarcted segments was atf significantly reduced , most likely due to wall thinning , as atf is prone to partial volume effects . in contrast , ptf and pti progressively decreased with increasing extent of scarring , as shown by lge cmr .
these results are in line with those of previous studies in which reductions in both ptf and pti were observed in nonviable scarred myocardium .
pti in control segments appeared to be somewhat lower than the expected value of unity for normal segments ( 0.91    0.08 ) .
this phenomenon has previously been observed in cardiomyopathy in both animal experiments and human studies [ 6 , 20 ] .
slight misalignment between pet and cmr segments may have occurred to additionally account for this reduction in pti .
furthermore , the presence of interstitial fibrosis in dilated cardiomyopathy may also explain this reduction in 
normal segments that remains undetected on lge cmr [ 21 , 22 ] . taking lge as a reference , the optimal cut - off values for discriminating between viable and nonviable myocardium
although this would reduce the data processing time , it would not affect the scanning protocol , as for both parameters a dynamic [ o]h2o pet scan in combination with a low - dose ct scan are required .
in addition , the sensitivity of pti exceeded that of ptf ( 91  % and 68  % , respectively ) , whereas for specificity the opposite pattern was observed ( 73  % and 78  % , respectively ) .
although further study is need to determine the cause of this discrepancy , as a potential clinical marker of viability pti may be favoured over ptf to reduce false - negative findings in patients who might benefit from revascularization .
it is of interest to note that , compared to ptf and pti , mbf performed relatively poorly in distinguishing viable from nonviable tissue , rendering it less suitable for viability imaging .
previous studies have indicated that the optimal cut - off value for pti is in the range 0.70.9 .
lge was used as a surrogate end - point of myocardial viability instead of functional recovery of dysfunctional myocardium after revascularization .
lge has been shown to be a good , but not perfect , marker of myocardial viability [ 15 , 17 ] .
therefore , the results should be interpreted with caution , and more studies are warranted to establish the value of parametric pti as a viability marker .
ptf and pti , obtained from a single [ o]h2o pet / ct scan , can be used as markers of myocardial viability in patients with coronary artery disease .
ptf and pti , obtained from a single [ o]h2o pet / ct scan , can be used as markers of myocardial viability in patients with coronary artery disease .
this article is distributed under the terms of the creative commons attribution license which permits any use , distribution , and reproduction in any medium , provided the original author(s ) and the source are credited .
 purposethe perfusable tissue index ( pti ) is a marker of myocardial viability . 
 recent technological advances have made it possible to generate parametric pti images from a single [ 15o]h2o pet / ct scan . 
 the purpose of this study was to validate these parametric pti images.methodsthe study population comprised 46 patients with documented or suspected coronary artery disease who were studied with [ 15o]h2o pet and late gadolinium - enhanced ( lge ) cardiac magnetic resonance imaging ( cmr).resultsof the 736 myocardial segments included , 364 showed some degree of lge . 
 pti and perfusable tissue fraction ( ptf ) diminished with increasing lge . 
 the areas under the curve of the pti and ptf , used to predict ( near ) transmural lge on cmr , were 0.86 and 0.87 , respectively . 
 optimal sensitivity and specificity were 91  % and 73  % for pti and 69  % and 87  % for ptf , respectively.conclusionpti and ptf assessed with a single [ 15o]h2o scan can be utilized as markers of myocardial viability in patients with coronary artery disease . 
Introduction
Materials and methods
Study population
PET/CT image acquisition
PET/CT image analysis
CMR image acquisition
CMR image analysis
Statistical analysis
Results
Baseline characteristics
PET/CT and CMR parameters
Predictive values for viability
Discussion
Conclusion
Open Access