PET/CT: Challenge for Nuclear Cardiology

Dynamic Data Acquisition

Cardiac PET requires dynamic data acquisition to define tracer kinetics for quantitation of blood flow and metabolism (28,29). In addition, cardiac motion effects in the data need to be minimized to improve spatial resolution in the moving heart. Most PET scanners allow electrocardiography gating of the data acquisition in a way similar to that for SPECT. However, for imaging vascular structures, additional respiratory gating may be required to correctly localize vascular activity and to improve the coregistration of PET and CT information (30,31). In order to fully exploit the possible dynamic information provided by PET and CT, list-mode acquisition may be the method of choice to retrospectively sort and correlate PET and CT data. Based on list-mode data, several physiologic signals such as electrocardiography and respiration can be used to categorize the information and provide imaging sets recognizing multiple gates (32). Figure 3 shows an example of the influence of respiratory gating on cardiac PET images. In this ¹³N-ammonia PET study, the list-mode data from 2 to 10 min after tracer injection were charted by histogram into 6 respiratory and 2 cardiac gates. The images show end-diastolic frames at end inspiration and at end expiration.

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FIGURE 3.

Influence of respiratory gating on cardiac motion is demonstrated in this ¹³N-ammonia study. With acquisition time of 10 min after tracer injection, list-mode data from 2 to 10 min were charted by histogram into 6 respiratory and 2 cardiac cycles. Images show end-diastolic frames in end inspiration and end expiration. Approximated, most apical position in both respiratory states is marked with yellow line. Maximal spatial difference is 8 mm. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.

The possibility for retrospective combinations of histogram settings provides another advantage for list-mode acquisition of short-lived isotopes such as ⁸²Rb and ¹⁵O-water. Conventional imaging protocols separate dynamic data acquisition from subsequent gated data collection. In list- mode, the entire dataset after a tracer application can be used to generate dynamic images to quantify blood flow. After tracer extraction from the blood, later data can be used to generate any combination of cardiac or respiratory gates.

Iterative Reconstruction

PET images are routinely reconstructed using iterative algorithms. The accelerated ordered-subset expectation maximization algorithm with normalization and attenuation weighting has become widely accepted and is routinely used in the clinic (33). In 3D mode, scatter can account for more than 50% of the collected counts. Scatter correction can be included in the reconstruction process using, for example, the single scatter simulation method (34,35). This scatter model relies on an estimate of the distribution of attenuating media in the field of view—an estimate that can accurately be provided by the CT data. In addition to scatter and AC, the combined PET/CT acquisition of functional and anatomic data may facilitate the incorporation of spatial constraints in the iterative algorithms (36,37). The basic assumption is that at positions in which there is a change of tissue type noticeable in CT, chances are high that the activity concentration also changes. Therefore, the reconstruction algorithm allows for larger changes at these positions, reducing the partial-volume effect and enhancing the visibility of small lesions. There are several methods to include the CT information in the PET-image reconstruction, one being the use of smoothed CT data as a weighting factor in statistical image reconstruction (36).

CT

With the introduction of electron-beam CT (EBCT) about 30 y ago, fast CT of the heart became possible (38). This technology was primarily introduced to measure regional coronary calcification as an early marker of CAD. Although large multicenter studies have been initiated to validate the diagnostic and prognostic value of this approach, EBCT technology has proven to be expensive and of limited usefulness outside cardiac imaging (39). The introduction of spiral CT in 1989 represented a major technical breakthrough, offering for the first time continuous-volume CT and hence opening the field of CT angiography (40). To increase the imaging volume and, hence, temporal resolution, multislice spiral CT was proposed in 1998. The advantage of multirow detectors is that the table feed per rotation can be increased according to the increased collimated width of the x-ray fanbeam (12). The temporal resolution of the system is determined by slice collimation, rotation time, and pitch, where pitch is defined as the ratio of table feed per rotation to the collimated x-ray width (41). Currently, multislice CT systems with 16 or 64 slices are recommended for cardiac imaging. The 64-slice systems provide 0.4-mm, nearly isotropic voxel resolution with a rotation time of only 0.33 s. Because noninvasive coronary angiography (i.e., CT angiography) is the most promising cardiac application of multislice CT, imaging parameters need to be optimized to meet the requirements of spatial and temporal resolution. The temporal resolution, defined as time required to acquire the necessary scan data to reconstruct a cardiac CT image, is about 100 ms for EBCT. For multislice CT, temporal resolution is dependent primarily on the time taken by the scanner to complete 1 gantry rotation but can be modified by using partial-scan reconstruction techniques. With these techniques, the image is reconstructed using data acquired from gantry rotations of approximately 240° (180° plus the total detector angle). By using optimized reconstruction algorithms, 180° of data in parallel geometry are extracted from the acquired data and reconstructed, improving the temporal resolution to one half the gantry rotation time. Because the rotation time of the 16-detector-row CT scanner is approximately 400 ms, the resulting temporal resolution is 200 ms. In view of these limitations in temporal resolution, the patient’s heart rate becomes an important issue, and most imaging protocols using 16-slice CT applications call for the use of a β-blocker to reduce the heart rate to less than 60 beats per minute. However, such acute pharmacologic interventions limit the widespread application of these imaging protocols and may not be required in view of newer multislice CT developments (42). A temporal resolution of about 80 ms appears feasible with the newest generation of multislice CT scanners. For a detailed discussion of multislice CT technology, we refer the reader to the reviews of Fuchs et al. (12) and Pannu et al. (43). Table 2 summarizes the imaging performance of currently available PET/CT instrumentation for cardiac imaging.

AC

The most important aspect of PET/CT is the use of CT information for AC. The effect of attenuation is greater for PET than for SPECT because of coincidence detection of radioactivity—the photon pair associated with an annihilation reaction has to cross the entire body, increasing the likelihood of attenuation. AC for PET is easier to apply, however, because the total attenuation of the pair of detected photons is independent of the origin of the radioactive event within the body. CT images of the chest require only a few seconds using multislice CT instrumentation, and low-dose CT images can be generated with good spatial resolution while minimizing radiation exposure to less than 1 mSv. However, because the attenuation factors for 511 keV have to be extrapolated from low-energy x-ray measurements, conversion factors have to be used for different tissue densities (e.g., heart, lung, and bone). These measurements have been validated in phantom studies and provide accurate measurements of tracer distribution in close agreement with measurements using conventional 511-keV transmission imaging (44).

In addition, coregistration of data becomes an important part of AC using CT, because transmission and PET emission data acquisitions are performed separately. The CT acquisition is completed within a few seconds, whereas PET data are collected over several minutes. During the PET acquisition, the influence of respiration is averaged throughout the entire imaging period, whereas the CT image represents only a small part of the respiratory cycle.

Thus, transmission and emission data may be misaligned. This is of great importance because the difference in tissue density between the heart and the surrounding lung is high. Misalignment of emission and transmission data produces artifacts in PET images that may affect the diagnostic performance of the test (Fig. 4) (45). Several protocols have been developed to account for these differences in respiratory state, but no standardized protocol for CT transmission scans has yet been developed. Loghin et al. demonstrated, in conventional rest/stress PET studies, that 21.7% of the studies showed misalignment artifacts typically in anterolateral or lateral segments of the left ventricle (45). Through manual coregistration of transmission and emission data, the artifacts could be removed.

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FIGURE 4.

Example of PET images attenuation corrected by misaligned CT image with artifacts in anterolateral wall of left ventricle. Artifacts resulted from motion associated with deep breathing of patient during CT scan. Resulting AC map is misaligned with PET emission data. Incorrect AC results in artifactual defects most commonly in anterolateral wall. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.

The advantage of CT is the option of repeating scanning before each tracer injection for AC. However, care has to be taken to minimize radiation exposure. The feasibility of CT scans with very low radiation exposures was demonstrated by Koepfli et al. (46). These investigators used a PET/CT system that was also equipped with the conventional rotating ⁶⁸Ge rod sources for transmission. In 7 patients, both conventional and CT-based AC with different tube currents was performed. These data were used for AC of dynamic ¹³N-ammonia studies. When comparing the myocardial blood flow values using tracer kinetic modeling, no differences for the different CT protocols tested were found. In a second group of 3 patients, consecutive CT scans with tube currents of 10 mA were acquired (corresponding to a radiation dose of as low as 0.05 mSv). Using the different CT scans for AC, the authors again found a high degree of reproducibility of blood flow values. Initial results from our own group confirmed this finding when using different CT protocols in 20 patients (slow CT: 99 mAs, 120 keV, 46 s; low dose: 20 mAs, 120 keV, 8 s; and ultra low dose: 13 mAs, 80 keV, 5 s). In the same patients, conventional PET was performed shortly after PET/CT (47). Relative ¹⁸F-FDG uptake was compared in 17 ventricular segments for both conventional PET and PET/CT and did not reveal significant differences for the 3 CT protocols; however, the radiation exposure was drastically different depending on the protocol—0.9, 0.4, and 0.1 mSv, respectively. An increased likelihood of patient motion was observed using the slow CT protocol, introducing artifacts. Although the entire duration of this particular scan was longer (46 s), the CT system is acquiring its slices so quickly that motion is accurately measured instead of being blurred. Taking these first observations into account, a fast, very-low-dose CT scan for AC offers clear advantages for cardiac PET/CT, although further validation is necessary.

Diagnosis of CAD

With the changing pathophysiologic understanding about CAD, it is becoming increasingly difficult to define the gold standard for disease detection. Conventionally, the presence of 50%–75% coronary stenosis is considered indicative of obstructive CAD. However, evidence is increasing that although the degree of stenosis may be related to the presence or absence of symptoms, the prognosis of patients cannot be predicted on the basis of angiographic criteria (5). A study has shown that a large subset of patients with acute myocardial infarction has coronary culprit lesions of less than 50% narrowing, limiting the use of the degree of stenosis as a predictor for acute ischemic syndromes (64). A consensus exists that indications for revascularization in patients with stable coronary disease should be based on evidence of myocardial ischemia (65). In symptomatic and asymptomatic patients with CAD, a large body of data indicates that the prognosis depends on the extent and severity of perfusion abnormalities during stress interventions (4,5). Therefore, the strategy of revascularization is aimed at reducing the individual risk to patients demonstrating a significant amount of ischemic myocardium at risk. On the other hand, in noninvasive tests such as MPI, the demonstration of normal results during maximal physical or pharmacologic stress is associated with a very low risk of cardiovascular complications (4). Therefore, the therapeutic management of patients with known CAD is based on functional characterization of the disease process. The combination of scintigraphic measurement of perfusion and CT depiction of coronary morphology may increase the accuracy of linking functional and morphologic data. This combination is expected to decrease the need for diagnostic cardiac catheterization and prove to be the method of choice for selecting patients for therapeutic intervention.

Noninvasive Coronary Angiography by CT Angiography

A large number of studies have recently been published demonstrating the increasing accuracy of multislice-CT angiography for the detection of CAD. With the availability of 16- and 64-slice scanners, the sensitivity and specificity for detection of significant coronary artery stenosis are exceeding 90% (43,66,67). Most investigators using 16-slice CT have recommended the use of β-blockers to reduce heart rate and, thus, the incidence of motion artifacts. With the introduction of the 64-slice CT scanner, the need to apply β-receptor blockade appears to be less critical (42). First experiences with the 64-slice CT scanner indicate that coronary arteries with a diameter of >1.5 mm can be evaluated without exclusion. Leschka et al. reported that none of the coronary segments of 67 consecutive patients needed to be excluded from analysis (42). CT correctly identified all 20 patients without significant stenoses on invasive angiography. Overall, sensitivity for classifying stenosis was 94%, specificity was 97%, positive predictive value was 87%, and negative predictive value was 99%. These results represent a significant improvement over the previous generations of multislice CT instrumentation. Using 4- to 8-slice CT, a sensitivity of 58%–86% for detection of coronary stenosis has been reported, but up to 32% of the vessels had to be excluded from analysis because of limited image quality. Using 16-slice CT, overall sensitivity, including all segments, was reported to range from 73% to 95% depending on the diameter of the segments, the mode of analysis, and the patient selection criteria (67,68). However, in some studies the evaluation was limited to branches having a diameter of >2 mm. Most studies were a single-center evaluation and involved patient populations with a high prevalence of CAD. Further prospective multicenter studies are needed to confirm the high diagnostic value of multislice CT imaging for the detection of CAD (69).

Multislice CT technology is expected to stabilize, resulting in longer product cycles and thus allowing for a more in-depth validation of this technology. However, there is little question that noninvasive coronary angiography will become a clinical reality, changing the workup of patients suspected of having obstructive CAD and the follow-up after surgical and percutaneous revascularization (70).

A drawback of CT angiography is its limited ability to correctly assess regional coronary stenosis in the presence of severe coronary calcification. Leschka et al., in their first evaluation of the 64-slice CT scanner, reported that coronary calcification was present in 18% of all coronary branches, resulting in beam-hardening artifacts and decreased visualization of the coronary lumen (42). Calcium deposits were responsible for most false-negative and all 24 false-positive results. However, all false-positive lesions showed coronary wall irregularities on invasive coronary angiography. Again, the use of MPI at the time of CT angiography may help to reduce the number of false-positive results, because normal perfusion reserve in segments distal to a coronary calcification may rule out a high-grade lesion. Berman et al., in a recent publication, demonstrated that only about 30% of patients with severe coronary artery calcification (Agatston score > 1,000) had stress perfusion defects (71).

Assessment of Blood Flow

The advantage of using PET in combination with CT to assess myocardial blood flow is the availability of tracers with a very short physical half-life, reducing the radiation dose and shortening the test.

¹⁵O-Water has a physical half-life of only 120 s and suitable tracer kinetics for the evaluation of myocardial blood flow. Because ¹⁵O-water is freely diffusible, the myocardial tracer uptake is linearly related to myocardial blood flow (72,73). However, because of its rapid kinetics, dynamic data acquisition is necessary to delineate the washing in and out of the tracer as a marker of myocardial perfusion. ⁸²Rb has physiologic characteristics similar to those of ^99mTc-labeled blood flow markers (74). In addition, its short half-life of 76 s allows the determination of rest and stress perfusion studies within 30 min. Several PET studies using ⁸²Rb as a blood flow marker have shown diagnostic accuracy higher than that of invasive procedures and SPECT perfusion imaging (Table 4). ⁸²Rb is a generator-derived radiopharmaceutical and, thus, does not require an on-site cyclotron for radioisotope production. Therefore, this radiopharmaceutical appears to be practical for the evaluation of rest and stress perfusion using PET/CT instrumentation (75). ¹⁵O-Water may be more suitable for quantitative blood flow measurements but still has to be considered experimental. An alternative tracer of blood flow is ¹³N-ammonia, which has a 10-min physical half-life but requires an on-site cyclotron for production. This tracer provides excellent image quality and has been validated extensively, demonstrating high diagnostic and prognostic accuracy for detection of CAD (76,77). Thus, qualitative and quantitative data on regional myocardial perfusion can be derived, and parameters such as coronary flow reserve and coronary vascular resistance can be determined (77,78).

Although PET has been well validated for detection of obstructive CAD, relatively few publications have documented the diagnostic superiority of PET in direct comparison with SPECT. Balanced CAD can be detected only by measuring regional flow reserve (75). PET appears to be more sensitive than SPECT for characterizing local stenosis and defining the extent of vascular impairment. Yoshinaga et al. demonstrated that abnormalities associated with coronary artery stenosis (<50%) were identified more frequently with PET flow reserve measurements than with SPECT (79). Future studies have to address the question of whether the higher diagnostic accuracy of PET, combined with the more rapid patient throughput, compensates for its higher cost and greater logistic infrastructure requirements. First experiences with ⁸²Rb suggest a potential role for PET in the work-up of patients with suspected or proven CAD (80).

Early Detection of CAD

Risk factor analysis and epidemiologic models based on the populations of the Framingham or PROCAM (Prospective Cardiovascular Münster) studies may allow individual risk assessment (81,82). Despite this sophisticated calculation of individual risk based on genetic and environmental risk factors, the accuracy of predicting acute myocardial infarction in an individual patient remains relatively low (83). Therefore, the need to develop additional biomarkers for the existence of CAD is of great importance. First results evaluating the presence of coronary calcification as incremental information in individual risk assessment are emerging. Pletcher et al. recently published a metaanalysis that demonstrated an adjusted relative risk of 2.1 (95% confidence interval, 1.6–2.9) for a coronary calcium score of 1–100. Relative risk estimates for higher scores ranged from 3.0 to 17.0. The authors concluded that coronary calcification is an independent predictor of a CAD event (84). Greenland et al., in a prospective observational study comparing Framingham risk score with coronary calcification score in 1,461 asymptomatic adults, recently showed that a high coronary calcification score can modify predicted risk based on Framingham risk score alone, especially among patients in the intermediate-risk category, for whom clinical decision making is most important (85). Shaw et al. recently demonstrated that the degree of coronary calcification measured by the Agatston score can identify patients with differing risk profiles (86).

A cohort of 10,377 asymptomatic individuals was followed for a mean of 5 y. The death rate was 2.4%. In a risk-adjusted model, coronary calcification score was an independent predictor of mortality. This observational study strongly suggested that coronary calcification score depicted by EBCT or multislice CT provides incremental prognostic information (86). Several prospective studies are currently under way to further investigate the prognostic value of coronary calcification score. Raggi et al. demonstrated that the absence of coronary calcification in a subgroup of diabetic patients was associated with an incidence of cardiac events comparable to that in nondiabetics without coronary calcification. On the other hand, in the diabetic population the risk was increased at each coronary calcification score level (87). Two studies have compared coronary calcification score and stress-induced perfusion abnormalities in asymptomatic adults (71,88). Anand et al. (88) observed a high prevalence of silent ischemia based on MPI in 18% of individuals with a coronary calcification score of 100–400. Patients with a coronary calcification score of >400 showed abnormal MPI in 45% of the cases. In contrast to these results, other studies suggest a lower incidence of MPI abnormalities associated with coronary calcification. Berman et al. (71) emphasize that normal MPI is often associated with significant coronary calcification. These investigators identified moderate and large stress perfusion defects (<10% of the left ventricle) in less than 10% of 1,195 asymptomatic patients with a coronary calcification score of <1,000. This finding implies a potential role for measuring coronary calcification before MPI to increase the sensitivity for diagnosing early nonobstructive CAD (71). Relative myocardial perfusion changes detectable by SPECT occur predominantly in advanced CAD with stenosis < 50%, whereas PET findings for coronary flow reserve may be abnormal in patients at risk for development of CAD. Several PET studies have documented a reduced myocardial flow reserve associated with risk factors such as hypercholesterolemia, diabetes mellitus, hypertension, and smoking (89–91). The use of endothelial dysfunction as a possible biomarker for active CAD is further supported by the notion that inflammatory processes not only are present in the area of plaque rupture but also involve much larger parts of the coronary vascular tree (92). The hypothesis of more widespread inflammatory changes in patients with acute coronary syndromes may also explain the observed impaired coronary flow reserve measurements in remote vascular territories of patients with acute myocardial infarction (93). Therefore, it is likely that the combination of coronary calcification and myocardial flow reserve measurements by PET may further enhance the management of individuals at risk of premature CAD. Relatively few data have been published defining the prognostic value of absolute flow reserve measurements as a marker of endothelial dysfunction. However, reports by Schachinger et al., Schindler et al., and Halcox et al. indicate that patients with impaired coronary vascular reactivity (determined invasively and noninvasively) have a worse prognosis than patients with a normal coronary response pattern (94–96). Several studies have indicated that the coronary flow reserve can be improved by lipid-lowering medication and other pharmacologic treatments (97–99). Quantitative evaluation of flow reserve or vascular reactivity may serve as an important surrogate endpoint for preventive therapeutic strategies. It is expected that this potential role will be broadened by combining PET and CT information. The time course of CAD progression or regression based on changes of calcification, soft-plaque formation, and endothelial function can be noninvasively defined and may serve as a comprehensive endpoint in the evaluation of new and established therapies (97,100–102).

Identifying Plaque Burden

Coronary calcification is one of the first biomarkers identifying atherosclerotic coronary lesions. However, several studies indicate that even in the absence of coronary calcification, plaques can be detected by CT, MRI, or ultrasound measurements (103–105). A recent study comparing CT with intravascular ultrasound revealed a 19% incidence of noncalcified lesions. There are no data indicating whether calcified or noncalcified lesions are more likely to rupture during an acute ischemic event. However, the increasing spatial resolution of multislice CT may allow the detection of vascular alterations in the form of calcified and noncalcified plaques. Becker et al. recently characterized various plaque subtypes using density measurements (Hounsfield units) (106). With the advent of molecular imaging, there may be an opportunity to enhance contrast in plaque imaging by combining scintigraphic data with CT characterization of individual plaques. The first application of this approach was provided by Rudd et al. (107), who observed higher ¹⁸F-FDG uptake in patients with symptomatic carotid lesions than in asymptomatic patients. Colocalization of ¹⁸F-FDG was observed in cells surrounding the lipid core near the fibrous cup of the plaque. These data suggest that it may be possible to identify the inflammatory component of atherosclerotic plaques in vivo, thereby allowing the biologic activity within plaques to be studied. However, ¹⁸F-FDG represents a relatively nonspecific marker for molecular processes. New radiopharmaceuticals that target the extracellular matrix proteinases or proteins that are upregulated during the inflammatory process may be of interest (108,109). First data using matrix proteinase inhibitors, as shown by Schafers et al. (108), indicate specific uptake of this tracer in a transgenic mouse model with atherosclerotic plaques. Other studies have indicated that radiolabeled annexin V can be used to identify apoptosis in macrophages infiltrating the plaque during the inflammatory phase (110,111). In addition, several adhesion molecules have been proposed as possible targets (112). The question remains as to whether the sensitivity and spatial resolution of PET/CT will allow an accurate coregistration of biologic and morphologic data to specifically delineate the inflammatory process involving coronary arteries. We recently introduced a radiopharmaceutical that targets exposed collagen after plaque rupture (113). Again, data in the APoE −/− transgenic mouse model indicate high tracer uptake in the areas of plaque rupture induced by wire ablation. In addition to the imaging of inflammatory components of plaque, imaging of thrombus deposition, which may be an early indicator of the development of acute ischemic syndromes, may be possible. Peptides targeting fibrin may be suitable for detecting the initiation of thrombus formation in patients with unstable CAD (114). These applications of molecular imaging for plaque characterization are in the early phases of preclinical evaluation. However, with the introduction of PET/CT, such experimental approaches can be transferred to the clinical environment and supported by the coregistration of CT and PET images. In addition to the evaluation of plaque biology, clinical data are needed to validate the prognostic value of such molecular imaging approaches. There is no question that PET/CT images will improve the evaluation of molecular signals, because targeted tracer signals require anatomic information. Future studies will have to show, however, whether PET/CT can show biologic signals in the beating heart and provide incremental prognostic information.

Assessment of Heart Failure

The results of multicenter trials on patients with heart failure indicate that up to 50% of patients with impaired left ventricular function have CAD (115). Because the treatment strategies for patients with CAD are different from those for patients with primary myocardial disease, such as dilated cardiomyopathy, accurate differentiation of ischemic and nonischemic heart disease is important. Again, with the advent of noninvasive coronary angiography by CT, the combination of PET and CT may help not only to separate patients with and without CAD but also to define the extent of reversible and irreversible ventricular dysfunction based on metabolic evaluation of the left ventricular myocardium (Fig. 6B). There are relatively few data available demonstrating the accuracy of CT angiography in patients with impaired left ventricular function. The quality of the contrast bolus in patients with low cardiac output may impair image quality. However, because of the reduced cardiac function, motion artifacts may be less prevalent in this population. Therefore, the newer generation of multislice CT scanners is expected to make possible the accurate detection of CAD in patients with impaired left ventricular function. PET has been validated extensively in the assessment of tissue viability using the combination of metabolic imaging with ¹⁸F-FDG and evaluation of myocardial blood flow. The extent of tissue viability predicts recovery of left ventricular function after revascularization (116). Based on coronary angiographic data provided by CT angiography and by the assessment of tissue viability, a noninvasive diagnostic workup may be possible. This possibility may be especially important for patients being considered for cardiac transplantation, when information about the viability of residual tissue and the extent of CAD, as defined by CT angiography, helps with the decision-making process.

The presence of mismatch between flow and metabolism is of high prognostic value (2,117,118). Several studies have indicated that the presence of metabolic activity in segments with severe dysfunction is associated with higher risk if these segments are not revascularized (118,119). A study has also shown that residual viability in dysfunctional myocardium is associated with less perioperative risk from the revascularization (120). Therefore, the combination of PET/CT in patients with severe left ventricular dysfunction may improve the diagnostic process and help avoid unnecessary invasive procedures. This comprehensive cardiac evaluation with PET/CT includes not only the CT angiography data and the myocardial tissue characterization but also the assessment of regional function through left ventricular ejection fraction (121). Therefore, with a single, noninvasive imaging procedure, the extent and severity of left ventricular dysfunction, the extent of tissue viability, and the overall extent of CAD can be characterized and used to risk-stratify the patient.

Besides being useful for the clinical characterization of patients with left ventricular dysfunction, PET/CT may be attractive for clinical research. This imaging modality provides surrogate endpoints for interventional studies, especially in the application of gene or cell therapy, which requires regional delineation of therapeutic interventions. Studies using reporter gene imaging have shown that the regional effects of gene therapy can be measured with tracer techniques such as PET/CT (122).