CT-Based Myocardial Perfusion Imaging-Practical Considerations: Acquisition, Image Analysis, Interpretation, and Challenges

Methods for non-invasive, cardiac risk assessment have historically relied on exercise stress testing with or without echocardiography or radionuclide imaging and pharmacological stress testing when appropriate. More recently, CT-based modalities like CT angiography (CTA) have been shown to reliably differentiate low from high-risk coronary disease. The advent of newer CT technology now allows for CT-based myocardial perfusion imaging (CTP) that provides functional information, that when analyzed with anatomic data from CTA, can provide a comprehensive risk assessment strategy. In this review, we discuss the research and implementation; as well as the quantitative, semiquantitative, and qualitative methods of image analysis of CT-based perfusion. We also discuss the present state of technology and challenges associated with the methodology. In each section, when appropriate, we provide some information regarding the translation of these methods being utilized in the international, multicenter CORE320 study that is evaluating the combined CT-based imaging (CTA and CTP) strategy of risk assessment in comparison to the combined reference standard of radionuclide myocardial perfusion imaging and invasive angiography.     

Myocardial Perfusion Imaging with Cardiac Computed Tomography: State of the Art

Cardiac computed tomography (CCT) has become an important tool for the anatomic assessment of patients with suspected coronary disease. Its diagnostic accuracy for detecting the presence of underlying coronary artery disease and ability to risk stratify patients are well documented. However, the role of CCT for the physiologic assessment of myocardial perfusion during resting and stress conditions is only now emerging. With the addition of myocardial perfusion imaging to coronary imaging, CCT has the potential to assess both coronary anatomy and its functional significance with a single non-invasive test. In this review, we discuss the current state of CCT myocardial perfusion imaging for the detection of myocardial ischemia and myocardial infarction and examine its complementary role to CCT coronary imaging.     

Diagnostic Performance of Hybrid Cardiac Imaging Methods for Assessment of Obstructive Coronary Artery Disease Compared With Stand-Alone Coronary Computed Tomography Angiography: A Meta-Analysis

Objectives

The current meta-analysis aimed to evaluate the diagnostic performance of hybrid cardiac imaging techniques compared with stand-alone coronary computed tomography angiography (CTA) for assessment of obstructive coronary artery disease (CAD).

Impact of both cardiac-CT and cardiac-MR on the assessment of coronary risk

Today's definition of coronary artery disease (CAD) comprises two forms: obstructive and non-obstructive CAD. The 31-72% chance of a life-threatening event-like a myocardial infarction-with non-obstructive CAD is well documented in numerous studies. The objective in modern strategies of diagnosis and therapy should therefore be expedient identification of patients at high risk for coronary events, who will benefit from a customized therapy. Before initiating diagnostic procedures of CAD, a well defined strategy should be pursued. There are two possible primary objectives: ASSESSMENT OF THE INDIVIDUAL RISK FOR A CORONARY EVENT: Assessment of the individual "absolute" risk for a coronary event is not possible using single traditional risk factors. The individual risk can be estimated by integrating several of the traditional risk factors into a scoring system. These so-called risk scores (e.g. Framingham score and Procam score), however, have been associated with shortcomings: insufficient discrimination of high-risk from low-risk individuals. The calcium score has therefore become increasingly established; this Agatston score is independent of the traditional risk factors, so there is no correlation between Agatston and Procam scores. Today, the calcium score is considered the superior test for identifying individuals at high risk for a coronary event and its use is recommended by the European Society of Cardiology (ESC) guidelines for prevention of cardiovascular diseases. PROOF OR EXCLUSION OF A HEMODYNAMICALLY SIGNIFICANT CORONARY STENOSIS: Another concept is the definitive proof or exclusion of a hemodynamically "significant" coronary narrowing. The probability of an obstructive CAD is traditionally assessed by the type of chest pain, age, gender and stress-ECG. In patients with a low probability of an obstructive CAD, cardiac catheterization is not indicated, whereas in patients with a high probability of a hemodynamically significant coronary stenosis, an invasive strategy should be performed. Since non-invasive coronary angiography (CTA) with cardiac-CT has been shown to provide a high negative predictive value, CTA (with good imaging quality) is suitable for ruling out a significant obstructive CAD in the group at intermediate risk for an obstructive CAD. Another approach could be a functional test to initially prove a relevant, inducible myocardial ischemia: In a large cohort it was shown that patients will only prognostically benefit from revascularization procedures if the ischemic myocardial area is greater than 10%. Therefore, the assessment of the extent of myocardial ischemia is the domain of modern stress imaging tests. Stress-echocardiography and myocardial scintigraphy have almost the same sensitivity (74-80%, 84-90%, respectively) and specificity (84-89%, 77-86%, respectively), which are considerably higher than for stress-ECG. Cardiac MR is most suitable for the assessment of myocardial perfusion, because it traces the first pass dynamics of gadolinium at rest and during stress in reproducible slices at an acceptable spatial and a high temporal resolution without ionizing radiation. Whether the non-invasive coronary angiography with cardiac-CT and the Adenosin-perfusion imaging with cardiac-MR will completely replace diagnostic cardiac catheterization and stress-echocardiography as well as myocardial scintigraphy remains to be evaluated in further studies.     

CT Perfusion: Ready for Prime Time

Advancements in computed tomography (CT) technology have revolutionized clinical practice, particularly regarding the noninvasive assessment of coronary artery disease (CAD). The versatility of cardiac CT has rendered multiple applications including assessment of cardiac structure and function, myocardial viability, and coronary anatomy. The merits of cardiac computed tomography angiography (CTA) have been proven for the detection, and particularly the exclusion, of CAD. However, CTA becomes limited in the presence of significant CAD. Its inability to consistently identify lesion-associated ischemia may necessitate additional radionuclide myocardial perfusion imaging. Myocardial computed tomography perfusion imaging (CTP) has emerged as a useful and convenient method to immediately assess myocardial ischemia. In this review, we discuss the current state of CTP including available technology, its performance to date from current literature, and future challenges to this field.     

Non-invasive assessment of low- and intermediate-risk patients with chest pain

Coronary artery disease (CAD) remains a significant global public health burden despite advancements in prevention and therapeutic strategies. Common non-invasive imaging modalities, anatomic and functional, are available for the assessment of patients with stable chest pain. Exercise electrocardiography is a long-standing method for evaluation for CAD and remains the initial test for the majority of patients who can exercise adequately with a baseline interpretable electrocardiogram. The addition of cardiac imaging to exercise testing provides incremental benefit for accurate diagnosis for CAD and is particularly useful in patients who are unable to exercise adequately and/or have uninterpretable electrocardiograms. Radionuclide myocardial perfusion imaging and echocardiography with exercise or pharmacological stress provide high sensitivity and specificity in the detection and further risk stratification of patients with CAD. Recently, coronary computed tomography angiography has demonstrated its growing role to rule out significant CAD given its high negative predictive value. Although less available, stress cardiac magnetic resonance provides a comprehensive assessment of cardiac structure and function and provides a high diagnostic accuracy in the detection of CAD. The utilization of non-invasive testing is complex due to various advantages and limitations, particularly in the assessment of low- and intermediate-risk patients with chest pain, where no single study is suitable for all patients. This review will describe currently available non-invasive modalities, along with current evidence-based guidelines and appropriate use criteria in the assessment of low- and intermediate-risk patients with suspected, stable CAD.     

Coronary computed tomography angiography in patients with stable coronary artery disease

The treatment of coronary artery disease (CAD), which is defined by stable anatomical atherosclerotic and functional alterations of epicardial vessels or microcirculation, focuses on managing intermittent angina symptoms and preventing major adverse cardiovascular events with optimal medical therapy. When patients with known CAD present with angina and no acute coronary syndrome, they have historically been evaluated with a variety of noninvasive stress tests that utilize electrocardiography, radionuclide scintigraphy, echocardiography, or magnetic resonance imaging for determining the presence and extent of inducible myocardial ischemia. Patient event-free survival, however, is largely driven by the coronary atherosclerotic disease burden, which is not directly assessed by functional testing. Direct evaluation of coronary atherosclerotic disease by coronary computed tomography angiography (coronary CTA) has emerged as the first line noninvasive imaging modality as it improves diagnostic accuracy and positively influences clinical management. Compared to functional assessment of CAD, coronary CTA-guided management results in improved patient outcomes by facilitating prevention of myocardial infarction. Other strengths of coronary CTA include detailed atherosclerotic plaque characterization and the ability to assess functional significance of specific lesions, which may further improve risk assessment and prognosis and lead to more appropriate referrals for additional testing, such as invasive coronary angiography.     

Relationship between CT coronary angiography and stress perfusion imaging in patients with suspected ischemic heart disease assessed by integrated PET-CT imaging.

BACKGROUND: Although computed tomography (CT) coronary angiography (CTA) provides detailed assessments of the anatomic extent of coronary artery disease (CAD), its value for predicting myocardial ischemia is unclear. We examined the value of CTA to identify the presence of ischemia, as determined by stress perfusion imaging, using integrated positron emission tomography (PET)-CT imaging. METHODS AND RESULTS: We studied 110 consecutive patients (median age, 57 years; 55% male) with suspected CAD undergoing stress rubidium 82 myocardial perfusion PET imaging and CTA in the same setting. Increasing degrees of CTA-detected luminal narrowing (<50%, 50%-70%, and >70%) were associated with reduced sensitivity with commensurate improvements in specificity for identifying myocardial ischemia both on a per-vessel basis and on a per-patient basis. Consequently, with increasing degrees of CTA-detected stenosis severity, the positive predictive value increased (14%, 26%, and 53%, respectively, on a per-vessel basis [P < .001] and 29%, 44%, and 77%, respectively, on a per-patient basis [P = .005]), whereas the negative predictive value was unchanged (97%, 97%, and 96%, respectively, on a per-vessel basis [P = not significant (NS)] and 92%, 91%, and 88%, respectively, on a per-patient basis [P = NS]). Receiver operating characteristic analysis revealed no differences between these 3 anatomic criteria (receiver operating characteristic areas of 0.66 +/- 0.07, 0.73 +/- 0.06, and 0.71 +/- 0.07, respectively [P = NS]) for identifying ischemia. Nearly half of significant angiographic stenoses (47%) occurred without evidence of myocardial ischemia, whereas 50% of normal PET studies were associated with some CTA abnormality. CONCLUSIONS: Despite an excellent negative predictive value, CTA is a poor discriminator of patients with myocardial ischemia. Conversely, a normal stress PET study is a poor discriminator of patients without evidence of non-flow-limiting (subclinical) coronary atherosclerosis. These results suggest potentially complementary roles of CT and perfusion imaging in the evaluation of patients with suspected CAD.     

Myocardial perfusion by CT versus hybrid imaging

Coronary computed tomography angiography (CTA) is a reliable diagnostic test for the anatomic diagnosis of obstructive coronary artery disease (CAD). Although coronary CTA shows high sensitivity and negative predictive value for detecting stenosis greater than or equal to 50% diameter, it is limited in its ability to diagnose myocardial ischemia. Advances in computed tomography (CT) technology alone and technology that hybridizes CT with single-photon emission CT and positron emission tomography allow for the combined anatomic and physiologic diagnosis of CAD. This article summarizes these combined technologies, emphasizing the merits and limitations of each technology and their clinical implications.     

Cardiac Imaging in the Diagnosis of Coronary Artery Disease

Coronary artery disease (CAD) continues to be a leading cause of morbidity and mortality worldwide. Although invasive coronary angiography has previously been the gold standard in establishing the diagnosis of CAD, there is a growing shift to more appropriately use the cardiac catheterization laboratory to perform interventional procedures once a diagnosis of CAD has been established by noninvasive imaging modalities rather than using it primarily as a diagnostic facility to confirm or refute CAD. With ongoing technological advancements, noninvasive imaging plays a pre-eminent role in not only diagnosing CAD but also informing the choice of appropriate therapies, establishing prognosis, all while containing costs and providing value-based care. Multiple imaging modalities are available to evaluate patients suspected of having coronary ischemia, such as stress electrocardiography, stress echocardiography, single-photon emission computed tomography myocardial perfusion imaging, positron emission tomography, coronary computed tomography (CT) angiography, and magnetic resonance imaging. These imaging modalities can variably provide functional and anatomical delineation of coronary stenoses and help guide appropriate therapy. This review will discuss their advantages and limitations and their usage in the diagnostic pathway for patients with CAD. We also discuss newer technologies such as CT fractional flow reserve, CT angiography with perfusion, whole-heart coronary magnetic resonance angiography with perfusion, which can provide both anatomical as well as functional information in the same test, thus obviating the need for multiple diagnostic tests to obtain a comprehensive assessment of both, plaque burden and downstream ischemia. Recognizing that clinicians have a multitude of tests to choose from, we provide an underpinning of the principles of ischemia detection by these various modalities, focusing on anatomy vs physiology, the database justifying their use, their prognostic capabilities and lastly, their appropriate and judicious use in this era of patient-centered, cost-effective imaging.     

Coronary CT Angiography as a Diagnostic and Prognostic Tool: Perspective from a Multicenter Randomized Controlled Trial: PROMISE

The PROMISE (Prospective multicenter imaging study for evaluation of chest pain) trial compared the effectiveness of coronary CT angiography and functional testing as initial diagnostic test for patients with suspicion for stable coronary artery disease (CAD). With 10,003 patients randomized at 193 sites, the PROMISE trial provides a snapshot of real-world care for this very common presentation. Over a median follow-up of 25 months, PROMISE did not find significant differences in major clinical events (composite endpoint 164 vs. 151, HR 1.04 (0.83–1.29); p?=?0.75) between the two strategies. Other major findings were the large discrepancy between estimates of pre-test likelihood and observed prevalence for obstructive CAD (≥50 %) and the proportion of noninvasive tests positive for ischemia or obstructive CAD (53 vs. 11 %; respectively) and the better efficiency of coronary computed tomography angiography (CTA) to select patients for invasive coronary angiography (ICA) who had obstructive CAD (72 vs. 48 % for coronary CTA and functional testing, respectively). Radiation exposure was higher in the CT arm compared to all functional testing but lower than for nuclear perfusion stress testing. Improvement of patient selection for diagnostic testing and risk stratification will be keys to increase efficacy and efficiency of management of patients with suspicion for stable CAD.     

Fractal Analysis of Dynamic Stress CT-Perfusion Imaging for Detection of Hemodynamically Relevant Coronary Artery Disease

BackgroundCombined computed tomography–derived myocardial blood flow (CTP-MBF) and computed tomography angiography (CTA) has shown good diagnostic performance for detection of coronary artery disease (CAD). However, fractal analysis might provide additional insight into ischemia pathophysiology by characterizing multiscale perfusion patterns and, therefore, may be useful in diagnosing hemodynamically significant CAD.ObjectivesThe purpose of this study was to investigate, in a multicenter setting, whether fractal analysis of perfusion improves detection of hemodynamically relevant CAD over myocardial blood flow quantification (CTP-MBF) using dynamic, 4-dimensional, dynamic stress myocardial computed tomography perfusion (CTP) imaging.MethodsIn total, 7 centers participating in the prospective AMPLIFiED (Assessment of Myocardial Perfusion Linked to Infarction and Fibrosis Explored with Dual-source CT) study acquired CTP and CTA data in patients with suspected or known CAD. Hemodynamically relevant CAD was defined as ≥90% stenosis on invasive coronary angiography or fractional flow reserve <0.80. Both fractal analysis and CTP-MBF quantification were performed on CTP images and were combined with CTA results.ResultsThis study population included 127 participants, among them 61 patients, or 79 vessels, with CAD as per invasive reference standard. Compared with the combination of CTP-MBF and CTA, combined fractal analysis and CTA improved sensitivity on the per-patient level from 84% (95% CI: 72%-92%) to 95% (95% CI: 86%-99%; P = 0.01) and specificity from 70% (95% CI: 57%-82%) to 89% (95% CI: 78%-96%; P = 0.02). The area under the receiver-operating characteristic curve improved from 0.83 (95% CI: 0.75-0.90) to 0.92 (95% CI: 0.86-0.98; P = 0.01).ConclusionsFractal analysis constitutes a quantitative and pathophysiologically meaningful approach to myocardial perfusion analysis using dynamic stress CTP, which improved diagnostic performance over CTP-MBF when combined with anatomical information from CTA.     

Ischemic heart disease: value of MR techniques

Background. The cardiovascular applications of magnetic resonance (MR) techniques in coronary artery disease have increased considerably in recent years. Technical advantages of MR imaging are the excellent spatial resolution, the characterization of myocardial tissue, and the potential for three-dimensional imaging. These characteristics allow the accurate assessment of left ventricular mass and volume, the differentiation of infarcted from normal tissue, and the determination of systolic wall thickening and regional wall motion abnormalities. Methods. In addition to the conventionally used spin-echo and cine-echo techniques, newer techniques such as myocardial tagging, ultrafast MR imaging and MR coronary angiography have been developed. These newer techniques allow a more accurate assessment of ventricular function (tagging), myocardial perfusion (ultrafast imaging), and evaluation of stenosis severity (MR coronary angiography). Particularly early detection and flow assessment of stenosed coronary arteries and bypasses by MR angiography would constitute a major breakthrough in cardiovascular MR imaging. Apart from the MR imaging techniques, cardiac metabolism may be well assessed using MR spectroscopy. This provides unique information on the metabolic behaviour of the myocardium under conditions stress-induced ischemia. However, the definite niche of cardiac MR spectroscopy has still to be settled. Conclusion. Currently, MR techniques allow the evaluation of anatomy and function (accepted use), perfusion and viability (development phase), and coronary angiography (experimental phase). A particular strength of MR imaging is that one single MR test may encompass cardiac anatomy, perfusion, function, metabolism and coronary angiography. The replacement of multiple diagnostic tests with one MR test may have major effects on cardiovascular healthcare economics and would outweigh the cost inherent to the MR angiography procedure.     

Relationship between noninvasive coronary angiography with multi-slice computed tomography and myocardial perfusion imaging.

OBJECTIVES: The aim of this study was to perform a head-to-head comparison between multi-slice computed tomography (MSCT) and myocardial perfusion imaging (MPI) in patients with an intermediate likelihood of coronary artery disease (CAD) and to compare non-invasive findings to invasive coronary angiography. BACKGROUND: Multi-slice computed tomography detects atherosclerosis, whereas MPI detects ischemia; how these 2 techniques compare in patients with an intermediate likelihood of CAD is unknown. METHODS: A total of 114 patients, mainly with intermediate likelihood of CAD, underwent both MSCT and MPI. The MSCT studies were classified as having no CAD, nonobstructive (<50% luminal narrowing) CAD, or obstructive CAD. Myocardial perfusion imaging examinations were classified as showing normal or abnormal (reversible and/or fixed defects). In a subset of 58 patients, invasive coronary angiography was performed. RESULTS: On the basis of the MSCT data, 41 patients (36%) were classified as having no CAD, of whom 90% had normal MPI. A total of 33 patients (29%) showed non-obstructive CAD, whereas at least 1 significant (> or =50% luminal narrowing) lesion was observed in the remaining 40 patients (35%). Only 45% of patients with an abnormal MSCT had abnormal MPI; even in patients with obstructive CAD on MSCT, 50% still had a normal MPI. In the subset of patients undergoing invasive angiography, the agreement with MSCT was excellent (90%). CONCLUSIONS: Myocardial perfusion imaging and MSCT provide different and complementary information on CAD, namely, detection of atherosclerosis versus detection of ischemia. As compared to invasive angiography, MSCT has a high accuracy for detecting CAD in patients with an intermediate likelihood of CAD.     

Assessment of coronary heart disease by CT angiography: current and evolving applications

Computed tomography angiography (CTA) of the heart is a rapidly evolving application for comprehensive assessment of coronary arterial anatomy, myocardial function, perfusion, and myocardial viability. Thus, cardiac CTA is capable of retrieving the most critical information for guiding the management of patients with suspected coronary heart disease (CHD). Ongoing technologic advancements have allowed acquiring such information within minutes, at radiation doses that are lower than those from conventional computed tomography imaging or common nuclear imaging techniques. Cardiac CTA has positioned itself as an imaging modality that may be well suited to fulfill central needs of cardiovascular medicine. This article reviews the evidence for the clinical utility of cardiac CTA in patients with suspected CHD.     

Cardiac PET-CT

Integrated positron emission tomography computed tomography (PET/CT) scanners allow a true integration of the structure and function of the heart. Myocardial perfusion PET provides a high sensitivity (91%) and specificity (89%) for the diagnosis of obstructive coronary artery disease (CAD). But, as with single photon emission CT, relative perfusion PET often uncovers only the territory subtended by the most severe coronary stenosis, leading to underestimation of the extent of CAD. In contrast, quantitative PET provides a noninvasive assessment of myocardial blood flow and coronary flow reserve and improves detection of preclinical and multivessel coronary atherosclerosis. Similarly, CT coronary angiography is an accurate means to image the entire continuum of anatomic coronary atherosclerosis from nonobstructive to obstructive CAD. However, not all coronary stenoses are hemodynamically significant and <50% of the patients with obstructive CAD on CT angiography demonstrate stress induced perfusion defects. Stress PET data complement the anatomic information on the CT angiogram by providing instant readings about the ischemic burden of coronary stenoses. Thus, combined PET/CT may be potentially superior to CT angiography alone for the guiding revascularization decisions. Further, fusion of the PET and CT angiogram images allows identification of the culprit stenosis in patients presenting with chest pain. Finally, the advances in molecular imaging and image fusion may soon make noninvasive detection of vulnerable coronary plaques a clinical reality. In summary, integrated PET/CT is a powerful new noninvasive modality that offers the potential for refined diagnosis and management of the entire spectrum of coronary atherosclerosis.     

Usefulness of cardiac magnetic resonance imaging for coronary artery disease detection

Cardiac magnetic resonance imaging (cMRI) is a promising non-invasive technique to assess the presence of coronary artery disease (CAD), which is free of ionizing radiation and iodine contrast. cMRI can detect CAD by angiographic methods or indirectly by perfusion stress techniques. While coronary angiography by cMRI remains limited to research protocols, stress perfusion cMRI is currently being applied worldwide in the clinical setting. Studies have shown good correlation between adenosine-induced stress myocardial perfusion cMRI and single-photon-emission computed tomography or positron emission tomography to detect CAD. Quantitative methods to analyze cMRI perfusion data have been developed in an attempt to provide a more objective imaging interpretation. Standardization of such quantitative methods, with minimal operator dependency, would be useful for clinical and research applications. Myocardial perfusion reserve (MPR), calculated using Fermi deconvolution technique, has been compared with well established anatomical and physiological CAD detection techniques. MPR appears to be the most accurate quantitative index to detect anatomical and hemodynamically significant CAD. Beyond physiological assessment of CAD, cMRI provides information regarding regional and global left ventricular function and morphology, myocardial infarction size, transmurality and viability. Such comprehensive information would require the performance of multiple tests if other modalities were used. This article describes current applications of cMRI for evaluation of patients with CAD.     

Prognostication of cardiac CT angiography

The rapidly emerging technique of cardiac computed tomography angiography (CTA) has enabled the anatomical assessment of coronary artery disease. CTA has very good diagnostic accuracy with the ability to detect nonobstructive from obstructive coronary artery disease and provides information on the presence of coronary artery calcification as well as on left ventricular function. Over the last few years, many prognostic studies have reviewed the outcome benefit of different scoring indices in predicting hard cardiac events. The following article will review the most recent literature available on the use of CTA in measuring luminal stenoses, identifying high-risk obstructive CAD, calcium plaque score, and LV function all in different models with their impact on the estimation of clinical risk. More recent data from a large multicenter registry supports the incremental benefit of CAD severity and LVEF as independent predictors of prognosis. Future directions and emerging applications such as the utility of CTA combined with perfusion analysis may lead to a new anatomical-functional diagnostic test that may provide optimal noninvasive assessment of coronary artery anatomy and be superior to invasive coronary angiography.     

Coronary artery imaging using MDCT and MRA

The potential benefits provided by new imaging technologies for the diagnostic evaluation of CAD are quantified by considering the expense, time, and associated risk of possible complications of traditional invasive angiography.……     

Positron emission tomography and molecular imaging

The use of positron emission tomography (PET) in cardiology is growing rapidly. Technical features make PET a strong technology for the non-invasive evaluation of cardiac physiology. It is currently considered the most reliable tool for the identification of myocardial viability and also allows accurate assessment of myocardial perfusion and detection of coronary artery disease (CAD). The unique feature of PET is that myocardial perfusion can be measured in absolute terms, improving sensitivity in the detection of multivessel of disease and also allowing evaluation of very early changes in coronary vasoreactivity and the progression or regression of CAD. Use of the newest generation of PET systems with integrated multislice computed tomography (CT) is becoming a standard technique for cardiac imaging. Since the PET and CT techniques ideally complement each other the combination is particularly attractive for the non-invasive assessment of CAD but also has other functions. Finally, there are also promising future applications that involve molecular imaging of cardiac targets, which may further enhance the clinical utility of PET and hybrid imaging.