The perfusable tissue index: a marker of myocardial viability

REVIEW The perfusable tissue index: A marker of myocardial viability Paul Knaapen, MD,a Ronald Boellaard, PhD,b Marco J. W. Go ¨ tte, MD, PhD,a Arno P. van der Weerdt, MD,a Cees A. Visser, MD, PhD,a Adriaan A. Lammertsma, PhD,b and Frans C. Visser, MD, PhDa INTRODUCTION

O-15–LABELED WATER AS A TRACER OF MBF

Detection of viable myocardium in patients with coronary artery disease and depressed left ventricular function is of great clinical importance. In contrast to nonviable myocardium, dysfunctional but viable myocardium has the capability of regaining contractility after revascularization.1 Various diagnostic techniques,2 including echocardiography,3 magnetic resonance imaging,4 and nuclear imaging,5 are available for detection of viable myocardium. Positron emission tomography (PET) with fluorine 18 –fluorodeoxyglucose (FDG) in combination with a myocardial blood flow (MBF) tracer, however, is considered to be the gold standard.6 The perfusable tissue index (PTI) is an alternative method for detecting myocardial viability. PTI reflects the fraction of the myocardium that is able to exchange water rapidly (ie, perfusable by water). It has been hypothesized that differentiation between viable and nonviable myocardium can be made based on the concept that areas of infarction (scar tissue) cannot exchange water rapidly. PTI is a PET-derived index, in which the water perfusable tissue fraction (PTF) is related to the anatomic tissue fraction (ATF). In combination with a transmission scan, PTF and ATF can be obtained with the use of oxygen 15–labeled water and carbon monoxide, respectively. This review discusses the background, principles, and validation of PTI. Because PTF is obtained from an O-15–labeled water MBF study, O-15– labeled water as a tracer of myocardial perfusion will first be discussed in brief.

Nearly two decades ago, the first validation studies were performed for quantification of MBF with the use of O-15–labeled water and PET. Bergmann et al7 demonstrated that regional distribution of O-15–labeled water correlated well with values obtained with the use of labeled microspheres, the accepted gold standard. Coronary artery stenoses could be detected accurately by measuring relative regional MBF in dogs during pharmacologically induced vasodilation.8 These results were successfully reproduced in patients with angiographically documented coronary artery disease.9 For absolute quantification of MBF, a single-compartment model can be used, which requires an arterial input function and accurate measurement of the myocardial radiotracer concentration. The latter issue remained difficult because of the partial volume effect (underestimation of true radiotracer concentration in regions smaller than twice the full width at half maximum of the resolution of the tomograph) and corresponding spillover effects (contamination of activity in one region with that from an adjacent one), resulting from the limited spatial resolution, which are enhanced by cardiac and respiratory motion. Although solutions have been proposed to correct for these effects (eg, assessment of cardiac dimensions for partial volume and spillover10 and electrocardiographic gating for cardiac motion corrections11), they are cumbersome and may themselves induce errors in estimating absolute MBF. Iida et al12 were the first investigators to correct for the partial volume effect and cardiac motion by including the PTF as an additional parameter in the standard single-compartment model. The PTF represents the amount of tissue that is capable of exchanging O-15– labeled water rapidly within a given region of interest (ROI) (in grams per milliliter). Bergmann et al13 introduced a model that not only corrected for the partial volume effect and cardiac motion but also for spillover effects. This model adds a third fitting parameter for spillover of arterial blood (Va). Consequently, three parameters are estimated from the dynamic O-15–labeled water emission images: MBF, PTF, and Va. A good correlation was found between MBF measured

From the Department of Cardiology,a and PET Center,b VU University Medical Center, Amsterdam, The Netherlands. Reprint requests: Paul Knaapen, MD, Department of Cardiology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; [email protected]. J Nucl Cardiol 2003;10:684-91. Copyright © 2003 by the American Society of Nuclear Cardiology. 1071-3581/2003/$30.00 ⫹ 0 doi:10.1016/S1071-3581(03)00656-1 684

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Figure 1. Example of transmission (A), blood pool (B), and extravascular density (C) images in a transaxial view from a healthy volunteer. Iterative reconstruction was used for the three images.

with O-15–labeled water and that with labeled microspheres in closed-chest dogs. MBF in human beings was 0.90 ⫾ 0.20 mL · g⫺1 · min⫺1, which increased to 3.55 ⫾ 1.15 mL · g⫺1 · min⫺1 during pharmacologically induced vasodilation.13 For acquisition of arterial time-activity curves (needed to quantify MBF), a ROI in either the left atrium or left ventricular chamber can be used (image-derived input function).13,14 These input curves correlated closely with those measured invasively by arterial cannulation.13,14 Over the years, numerous studies measuring MBF successfully with the use of O-15–labeled water in patients with a variety of pathophysiologic conditions have been reported.15 PRINCIPLES AND VALIDATION OF PTF, ATF, AND PTI Having introduced the PTF, Iida et al16 compared this parameter with the ATF. The ATF represents the mass of extravascular tissue in a ROI and was first developed by Rhodes et al17 for lung tissue. This technique calculates extravascular tissue density (in grams per milliliter) by subtracting a blood pool image from a transmission image. The transmission image, routinely acquired for attenuation correction purposes, comprises both vascular and extravascular tissue. A blood volume image derived from an O-15–labeled carbon monoxide scan represents the vascular space only. Subtraction of the blood volume image from the transmission image, normalized to the density of blood (1.06 g/mL), provides a quantitative image of extravascular tissue density. Figure 1 shows typical transmission,

blood volume, and extravascular density images from a healthy volunteer. In theory, PTF and ATF should provide similar results for normal myocardium because both underestimate true radioactivity in the myocardium to the same degree, provided that the spatial resolution of emission and transmission images is identical. The ratio of PTF and ATF, the so-called perfusable tissue index (PTI), should therefore equal unity in normal myocardium, assuming that all extravascular tissue (ie, myocardium) is able to exchange water rapidly. Figure 2 gives a diagrammatic representation of ATF, PTF, and PTI. Because the single-compartment model cannot distinguish myocardium from venous blood,16 PTF is approximately 10% higher than ATF, as venous blood volume within the myocardium amounts to approximately 0.10 mL per gram of net myocardium.18 PTI for normal myocardium should therefore be close to 1.1. PTI is independent of not only partial volume effects (and cardiac motion) but also the size of the ROI. A larger ROI will contain more extramyocardial components and result in an equal decrease in both PTF and ATF. PTI will therefore remain unaffected by changes in ROI definition. In a study by Iida et al16 the mean ATF values for 9 healthy volunteers were 0.62 ⫾ 0.05 g/mL, 0.64 ⫾ 0.04 g/mL, and 0.62 ⫾ 0.05 g/mL for the septal, anterior, and lateral regions, respectively. The mean PTF values were 0.86 ⫾ 0.08 g/mL, 0.72 ⫾ 0.09 g/mL, and 0.71 ⫾ 0.05 g/mL for the same regions. Calculated from these results, the values for PTI were 1.40 ⫾ 0.19, 1.14 ⫾ 0.13, and 1.14 ⫾ 0.10, respectively (Table 1). These values confirmed the expected values for the anterior and lateral regions. PTF and consequently PTI for septal regions were significantly higher as a result of spillover

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of activity from the right ventricular chamber (see below). Four patients with previous myocardial infarction showed comparable results for ATF (0.64 ⫾ 0.25 g/mL) but consistently reduced values for PTF (0.44 ⫾ 0.16 g/mL) in the infarcted segments. Therefore PTI was also reduced in the infarcted segments (0.71 ⫾ 0.26) (Table 2). The disparity between ATF and PTF was thought to be the result of the inability of scar tissue to exchange water rapidly, leading to a reduction in PTF. ATF is preserved in scar tissue because it only represents extravascular tissue density, independent of its structure. PTI and, to a lesser extent, PTF are thus able to identify infarcted myocardium (Figure 2). This has recently been confirmed histochemically in an experimental canine study.19 Both PTF and PTI were decreased significantly in infarcted segments. ATF did not differ between normal and infarcted segments. ATF, however, can be reduced in infarcted segments as a result of reduced wall thickness, even after adjustment of the ROI size. This effect is caused by the partial volume effect.16,19 An overview of the studies with sufficient ATF, PTF, and PTI data in healthy volunteers and in patients or dogs with dysfunctional myocardium is given in Tables 1 and 2. The values for PTI vary considerably for the studies in Table 1, mainly because of differences in PTF (for septum and nonseptum regions). More studies in healthy volunteers are needed. Table 2 demonstrates a consistent reduction of PTI in dysfunctional myocardium. PRACTICAL ISSUES Administration Protocol

Figure 2. Diagrammatic representation of a ROI containing both O-15–labeled water perfusable and nonperfusable tissue. A, Volume of ROI. B, ATF. C, PTF excluding the nonperfusable tissue from the ROI. PTI equals the ratio of PTF and ATF and represents the fraction of anatomic tissue that is perfusable by water. (Reproduced with permission from Yamamoto et al, Circulation 1992;86:167-78.)

The overestimation of PTF in the septum mentioned above can be explained by the fact that O-15–labeled carbon dioxide was used in that particular study.16 O-15–labeled carbon dioxide converts to O-15–labeled water in the lung by the enzyme carbonic anhydrase. As a result, the concentration in the right ventricular chamber is the same as that in venous blood, which cannot be distinguished from tissue.7,16 Spillover from the right ventricular chamber will therefore cause an overestimation of PTF. This problem can be solved by intravenous administration of O-15–labeled water, either by slow infusion or by bolus injection. With this mode of administration, the right ventricular chamber will be at arterial concentration and can thus be separated from tissue. Studies comparing different administration protocols (O15–labeled carbon dioxide inhalation, O-15–labeled water slow infusion, and O-15–labeled water bolus injection) have demonstrated that bolus injection of O-15– labeled water provides the most accurate results for PTF and MBF.20,21 In particular, there is no overestimation of

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Table 1. Mean values for ATF, PTF, and PTI in healthy volunteers

ATF (g/mL) Author

No. of subjects

Administration protocol

Septal

Anterior

Lateral

All

Iida et al16 Yamamoto et al26 Gerber et al23

9 8 6

O-15–labeled carbon dioxide O-15–labeled carbon dioxide O-15–labeled water

0.62 0.63 0.55

0.64 0.68 0.63

0.62 0.66 0.64

0.63 0.66 0.61

Table 2. Mean values for ATF, PTF, and PTI for dysfunctional myocardium

No. ATF (g/mL) PTF (g/mL) PTI of subAuthor jects Subjects Dysfunctional Remote Dysfunctional Remote Dysfunctional Remote Iida et al16

4 Human beings* Yamamoto 26 Human beings* et al26 Iida et al19 12 Dogs* Itoh et al28 15 Human beings

0.64 ⫾ 0.25

0.69 ⫾ 0.02

0.44 ⫾ 0.16

0.79 ⫾ 0.03

0.71 ⫾ 0.26

1.15 ⫾ 0.07

0.74 ⫾ 0.07

0.72 ⫾ 0.06

0.51 ⫾ 0.15

0.72 ⫾ 0.07

0.69 ⫾ 0.19

1.00 ⫾ 0.07

0.48 ⫾ 0.05 0.68 ⫾ 0.10

0.48 ⫾ 0.09 0.64 ⫾ 0.08

0.31 ⫾ 0.13 0.45 ⫾ 0.08

0.49 ⫾ 0.10 0.47 ⫾ 0.06

0.62 ⫾ 0.24 0.66 ⫾ 0.09

1.02 ⫾ 0.11 0.74 ⫾ 0.04

*Documented myocardial infarction in dysfunctional myocardium.

PTF in the septum. A further improvement in the accuracy of PTF in the septum has been achieved by correcting for both left and right ventricular spillover.20 Although the bolus injection technique yields the best results, the fast transit of activity through the cardiac chambers results in high count densities that can lead to dead-time losses. This effect, especially for PET scanners with relatively low count rate performance, can result in unreliable image-derived input curves. The mode of administration of O-15–labeled water must be optimized according to the technical capabilities of the PET scanner. Interpretation of MBF Values It needs to be emphasized that implementation of the PTF within the O-15–labeled water model results in MBF values that represent flow in perfusable tissue only.12 In normal myocardium this will represent actual flow. In contrast, after myocardial infarction, scar tissue is not able to exchange water rapidly and therefore will not be included in the MBF calculation. This results in higher MBF values compared with other flow tracers. This effect has been demonstrated in a direct comparison between O-15–labeled water and labeled microspheres in infarcted dog hearts.22 Comparison between nitrogen 13–labeled ammonia and O-15–labeled water in human

infarcted myocardium showed similar results (N-13– labeled ammonia estimates transmural myocardial blood in infarcted myocardium, making it comparable to the microsphere technique).23 MBF in perfusable tissue (MBFp) can be converted to MBF per units of mass of total tissue (MBFt) by multiplying MBFp by PTI (Figure 2). MBFt represents transmural blood flow and allows comparisons to be made with other techniques such as N-13–labeled ammonia and labeled microspheres. The correlation between N-13–labeled ammonia and MBFt in human dysfunctional myocardium, however, was less than perfect in a study by Gerber et al23 (r ⫽ 0.51, P ⬍ .05). More studies are needed to account for these differences. Flow Heterogeneity Although the hypothesis that PTI in infarcted myocardium is reduced because of the inability of scar tissue to exchange water rapidly is an attractive one, the truth might be more complex. In regions of acute and old myocardial infarction, often a state of low flow rather than zero flow exists. Diffusion of O-15–labeled water in necrotic tissue of old myocardial infarction in dogs does occur.24 Theoretically, a region with low flow should have normal PTI. Furthermore, a typical ROI placed on dysfunctional myocardium will most likely contain a

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PTF (g/mL) Septal 0.86 0.77 0.58

PTI

Anterior

Lateral

All

Septal

Anterior

Lateral

All

0.72 0.70 0.58

0.71 0.67 0.60

0.76 0.71 0.58

1.40 1.23 1.05

1.14 1.03 0.94

1.14 1.02 0.95

1.22 1.08 0.99

mixture of intact myocytes and necrotic tissue with varying degrees of perfusion. Using computer simulations, Herrero et al24 demonstrated that a heterogeneous flow pattern (4 different flows with a minimum of 0.10 mL · min⫺1 · g⫺1) can cause an underestimation of PTI. PTI was consistently lower for heterogeneously perfused regions and decreased further in regions with very low absolute flow. To evaluate the clinical importance of these findings, heterogeneity of extreme low flow (25% of 0.01 mL · min⫺1 · g⫺1) and normal flow (75% of 1.0 mL · min⫺1 · g⫺1) was simulated showing little influence on the expected PTI (0.76). This probably reflects more realistic differences of flow between scar tissue and well-perfused myocardium. Nevertheless, the simulations by Herrero et al indicate that flow heterogeneity might result in a bias in PTI. To what extent this affects PTI as a marker of viability needs to be determined in future studies. Recently, in an ischemic porcine model, Scha¨ fers et al25 demonstrated a decrease in PTF and PTI after administration of dipyridamole whereas MBF increased moderately. Vasodilation can induce steal effects and a pressure drop behind a coronary stenosis. This could cause flow to become inhomogeneous. In addition, a pressure drop results in the shutdown of the microvascular bed through vasoconstriction, thereby actually reducing the perfused vascular bed. Both explanations could be responsible for the reduction in PTF and PTI. ATF Spillover Artifacts ATF is defined by the extravascular myocardial tissue density when ROIs are placed on the myocardium. The heart, however, is surrounded by other anatomic structures, potentially leading to spillover artifacts. The anterior myocardial wall is especially prone to spillover effects from the adjacent chest wall. Overestimation of ATF might occur with a corresponding underestimation of PTI as PTF is unaffected. Iida et al19 found a significant ATF difference between open- and closedchest dogs, confirming this spillover effect. The clinical relevance is probably limited, because ATF values for anterior myocardium in healthy volunteers are comparable to those of other regions (Table 1). The effects of

ATF spillover might be more pronounced in patients with dilated cardiomyopathies, as these hearts have larger contact areas to adjacent structures such as the chest wall. More studies in these patient groups are needed. Blood Pool Imaging Although blood pool images for calculating ATF are best acquired with the use of O-15–labeled carbon monoxide, FDG has been used. By considering only the early images after tracer injection (45 seconds), FDG predominantly reflects the blood pool before significant extraction into the myocardium has occurred. Gerber et al23 compared these two different methods of calculating ATF in healthy volunteers and demonstrated a good correlation (r ⫽ 0.77, P ⬍ .01). Whether this correlation holds true for patients with ischemic heart disease and increased anaerobic glycolysis remains to be investigated. PTI AS A MARKER OF VIABLE MYOCARDIUM PTI reflects the fraction of extravascular tissue being perfused by water. A decrease in PTI indicates a relative decrease in perfused tissue. Assuming the nonperfused fraction to be scar tissue, the reduction of PTI is a measure of the amount of damaged myocardium. Under certain circumstances, dysfunctional myocardium has the capability of regaining function after revascularization. This myocardium is in a state of hibernation and is said to be viable.1 Dysfunctional myocardium with a normal or near normal PTI would be expected to be viable because the amount of scar tissue is limited. In contrast, dysfunctional myocardium with a reduced PTI is less likely to be viable because more scar tissue is present. This hypothesis of PTI being a marker of viability was first tested more than a decade ago. To date, four studies on the relationship between PTI and myocardial viability have been published (Table 3). Yamamoto et al26 estimated viability in 15 patients with old myocardial infarction by determining a metabolism-flow match or mismatch with the use of FDG and O-15–labeled water.

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Table 3. Comparison of studies predicting viability based on PTI

Author Yamamoto et al26 de Silva et al27 Gerber et al23 Itoh et al28 Combined

Cutoff value

No. of Compared with segments Sensitivity Specificity

PTI ⬎ 0.7

O-15–labeled water and FDG PTI ⬎ 0.7 Recovery of function PTI ⬎ 0.7 Recovery of function PTI ⬎ 0.9* Recovery of function PTI ⬎ 0.7 Recovery of function PTI Recovery of function

15

56 (5/9)

12 33 30 15 90

100 (7/7) 100 (26/26) 75 (12/16) 71 (5/7) 89 (50/56)

PPV

NPV

100 (6/6)

100 (5/5)

0.60 (6/10)

100 (5/5) 100 (7/7) 86 (12/14) 100 (8/8) 94 (32/34)

100 (7/7) 100 (26/26) 86 (12/14) 100 (5/5) 96 (50/52)

100 (5/5) 100 (7/7) 75 (12/16) 80 (8/10) 84 (32/38)

PPV, Positive predictive value; NVP, negative predictive value. *FDG used for blood pool image and calculation of ATF.

Nine patients had a mismatch pattern and were thus considered to be viable; six patients were considered to be nonviable. Mean PTI in the viable group was 0.75 ⫾ 0.14 and was significantly higher than that in the nonviable group (0.53 ⫾ 0.12) (P ⬍ .01). The differences in PTI were solely due to differences in PTF (0.54 ⫾ 0.07 g/mL vs 0.36 ⫾ 0.06 g/mL, P ⬍ .01), as ATF was similar in both groups (0.72 ⫾ 0.08 g/mL vs 0.70 ⫾ 0.07 g/mL, P ⫽ not significant). Furthermore, PTI was determined in 11 patients (12 dysfunctional segments) who had acute myocardial infarction with patency of the infarct-related artery, either spontaneously or after successful thrombolysis. An echocardiogram was obtained on the same day as the PET study (1-4 days after admission to the hospital) and repeated at 4 months’ follow-up to assess improvement of cardiac function. Of 12 dysfunctional segments, 7 showed improved systolic wall thickening at follow-up. PTI in the recovery segments was significantly higher than in the nonrecovery segments (0.88 ⫾ 0.10 vs 0.53 ⫾ 0.11, P ⫽ .017). In both patient groups (old myocardial infarction and acute myocardial infarction) PTI in remote myocardial control regions with normal function was equal to that in healthy volunteers. PTI in recovery segments of both patient groups was reduced slightly compared with control regions, although no statistical difference was reached. This indicates that although some myocardium was compromised, enough survived to regain function. In the acute myocardial infarction patient group, recovery occurred only in segments with a PTI of at least 0.7. This suggests that at least 70% of the myocardium needs to be able to exchange water rapidly in order to improve contractile function. de Silva et al27 determined PTI in 12 patients with previous myocardial infarction shortly before revascularization by coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. Of the 33 dysfunctional segments, 26 improved after revascularization. Another 26 segments had no wall motion abnor-

malities before the procedure. These segments without dysfunction were used as control regions. MBFp in the control segments (0.97 ⫾ 0.22 mL · min⫺1 · g⫺1) was significantly higher (P ⬍ .001) than in both recovery (0.73 ⫾ 0.18 mL · min⫺1 · g⫺1) and nonrecovery (0.45 ⫾ 0.11 mL · min⫺1 · g⫺1) segments. Although MBFp showed significant differences between the three groups, there was great overlap. The values of PTI in recovery segments were reduced slightly compared with those in control segments (0.99 ⫾ 0.15 vs 1.10 ⫾ 0.15, P ⫽ .013). All recovery segments had a PTI greater than 0.7. In the nonrecovery segments PTI was significantly lower than in both control and recovery segments (0.62 ⫾ 0.06, P ⬍ .02) and was always less than 0.7. Therefore PTI could discriminate accurately between viable and nonviable tissue with the use of a cutoff value of 0.7, confirming the data of Yamamoto et al. Gerber et al23 further tested PTI as marker of viability in 30 patients with dysfunctional anterior myocardium scheduled for revascularization. PTI was significantly higher in viable tissue (1.07 ⫾ 0.07) than in nonviable tissue (0.78 ⫾ 0.05) (P ⬍ .01). A cutoff value of 0.9 yielded the best diagnostic accuracy, with a sensitivity of 75% and a specificity of 86%. Recently, Itoh et al28 found reduced PTI in 8 nonrecovery segments after revascularization (0.59 ⫾ 0.04) compared with 7 recovery segments (0.73 ⫾ 0.06) (P ⬍ .0001). A cutoff value of 0.7 yielded the best diagnostic accuracy. The cutoff value in the study by Gerber et al is higher than that in the other studies. This can be explained by the method of determining ATF in this study. The blood pool images were derived from the early phase images after injection of FDG, resulting in lower ATF values than found in the three other studies. FDG may have a larger volume of distribution than O-15–labeled carbon monoxide, especially in patients with ischemic myocardium. The lower ATF in turn also causes PTI to be higher, explaining the discrepancy in cutoff value for PTI. In

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Table 3 a total of 90 segments from these 4 studies have been pooled, comparing PTI in relation to recovery of function. Overall sensitivity and specificity are 89% and 94%, respectively, and compare favorably with those of other techniques for assessing viability.2 It should be noted that although these results are promising, they are based on studies from a limited number of centers in a small number of patients. Furthermore, data from direct comparison with other techniques of detecting viable myocardium are scarce.26,27 One reason for the lack of more extensive data on PTI is that only a few centers worldwide are presently equipped to measure MBF with the use of O-15–labeled water and carbon monoxide. Suggestions have been made to use only PTF as a marker of viability.29 The rationale for using PTF rather than PTI is the fact that ATF has been shown to be relatively constant for viable, nonviable, and control regions, as ATF only represents extravascular tissue, independent of its composition. PTF determines the fluctuations in PTI in pathologic conditions and can therefore also be used for detecting viable myocardium. Furthermore, this approach obviates the need for blood pool imaging. Although using PTF instead of PTI is convenient, PTF values depend on ROI size,12 making this approach more operator-dependent. In addition, ATF has been shown to decrease in a relatively thin myocardial wall after infarction.12-16 Taking ATF out of the equation could lead to erroneous conclusions. On the other hand, determination of PTI requires not only the ability to produce O-15–labeled water and carbon monoxide with the use of an onsite cyclotron but also full cooperation of the patient. PTI can only be calculated after a transmission scan, a dynamic O-15–labeled water emission scan, and a static O-15–labeled carbon monoxide scan are obtained. Motion artifacts can therefore be an important source of error. For determination of the best strategy, either PTI or PTF, more investigations are required in which both techniques are compared directly as well as with other techniques. A multicenter pilot trial in Japan recently showed promising results concerning the variability of PTF in healthy volunteers, provided ROI definition was standardized.30 CONCLUSION PTI is a promising technique for detecting viable myocardium. The need for a PET scanner, an onsite cyclotron, and expertise regarding the production and administration of O-15–labeled water and carbon monoxide results in a tool that is only available in a limited number of centers worldwide. Consequently, studies reporting on the accuracy of PTI as a viability marker are limited. However, it is worthwhile to explore the value of PTI further, taking into account the clinical importance

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of detecting viability. In addition, with the increasing number of PET scanners and onsite cyclotrons, this technique will most likely become more accessible in the future. Finally, PTI can be obtained in less than an hour (30-45 minutes), and radiation burden is low compared with other nuclear medicine procedures such as FDG and thallium imaging. Future studies comparing PTI directly with other established techniques for assessing viable myocardium are needed to gain more insight into the clinical value of PTI. Acknowledgment The authors have indicated they have no financial conflicts of interest.

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