Fatty Acid Imaging of the Heart

Imaging metabolic processes in the human heart yields valuable insights into the mechanisms contributing to myocardial pathology and allows assessment of the efficacy of therapies designed to treat cardiac disease. Recent advances in fatty acid (FA) imaging using positron emission tomography (PET) include the development of a method to assess endogenous triglyceride metabolism and the design of new fluorine-18 labeled tracers. Studies of patients with diabetes have shown that the heart is resistant to insulin-mediated glucose uptake and that metabolism of nonesterified FA is upregulated. Cardiac PET imaging has also recently shown the increase in myocardial FA uptake seen in obese patients can be reversed with weight loss. And a pilot study of patients with chronic kidney disease demonstrated that PET imaging can reveal myocardial metabolic alterations that parallel the decline in estimated glomerular filtration rate. Recent advances in FA imaging using single photon emission computed tomography (SPECT) have been accomplished with the tracer β-methyl-p-[¹²³I]-iodophenyl-pentadecanoic acid (BMIPP). Two meta-analyses showed this imaging technique has a diagnostic accuracy for the detection of obstructive coronary artery disease that compares favorably with SPECT myocardial perfusion imaging and that BMIPP imaging yields excellent prognostic data in patients across the spectrum of coronary artery disease. A recent multicenter study of patients presenting with acute coronary syndromes found BMIPP SPECT imaging has greater diagnostic sensitivity than, and enhances the negative predictive value of, clinical assessment alone. Because of their exquisite sensitivity, nuclear imaging techniques facilitate the study of physiologic processes that are the key to our understanding of cardiac metabolism in health and disease.     

SPECT Imaging for Detecting Coronary Artery Disease and Determining Prognosis by Noninvasive Assessment of Myocardial Perfusion and Myocardial Viability

Basic knowledge of active and passive transport mechanisms for concentrating monovalent cations in myocardial cells led to the investigation of the application of radioisotopes of potassium, thallium, rubidium, and ammonia to the in vivo noninvasive assessment of regional myocardial perfusion and viability utilizing gamma camera or positron emission tomographic (PET) imaging technology. Subsequently, technetium-99m (Tc-99m)-labeled isonitriles (sestamibi and tetrofosmin), which bind to mitochondrial membranes, emerged as superior imaging agents with single photon emission tomography (SPECT) imaging. When any of these imaging agents are injected intravenously during either exercise or pharmacologic stress, myocardial defects in tracer uptake represent either abnormal regional flow reserve or myocardial scar reflecting of coronary artery disease (CAD). The major clinical indications for stress SPECT or PET myocardial perfusion imaging are for detection of CAD as the cause of chest pain and risk stratification for prognostication. Patients with normal stress myocardial perfusion scans have an excellent prognosis with <1.0% annual rate future annual death or nonfatal infarction. The greater the extent and severity of ischemic perfusion defects (defects seen on stress images but improve on resting images), the greater the subsequent death or infarction rate during follow-up. Rest imaging alone is performed for determination of myocardial viability in patients with CAD and severe left ventricular dysfunction. Myocardial segments showing >50% uptake compared to normal uptake have a better long-term outcome with revascularization than with medical therapy with enhanced left ventricular function and improved survival. Other applications of SPECT imaging include the evaluation of cardiac sympathetic function, assessment of myocardial metabolism in health and disease, and molecular imaging of coronary atherosclerosis and myocardial stem cell therapy.     

Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography

The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi [11C]hydroxyephedrine. Blood and myocardial tracer kinetics were assessed using a regions-of-interest approach. In normal volunteers, blood 11C activity cleared rapidly, whereas myocardium retained 11C activity with a long tissue half-life. Relative tracer retention in the myocardium averaged 79 +/- 31% of peak activity at 60 minutes after tracer injection. The heart-to-blood 11C activity ratio exceeded 6:1 as soon as 30 minutes after tracer injection, yielding excellent image quality. Little regional variation of tracer retention was observed, indicating homogeneous sympathetic innervation throughout the left ventricle. In the transplant recipients, myocardial [11C]hydroxyephedrine retention at 60 minutes was significantly less (-82%) than that of normal volunteers, indicating only little non-neuronal binding of the tracer in the denervated human heart. Thus, [11C]hydroxyephedrine, in combination with dynamic PET imaging, allows the noninvasive delineation of myocardial adrenergic nerve terminals. Tracer kinetic modeling may permit quantitative assessment of myocardial catecholamine uptake, which will in turn provide insights into the effects of various disease processes on the neuronal integrity of the heart.     

Myocardial perfusion and viability by positron emission tomography in infants and children with coronary abnormalities: correlation with echocardiography,coronary angiography,and histopathology

OBJECTIVES: This study was designed to assess the feasibility and accuracy of positron emission tomography (PET) imaging in infants and children. BACKGROUND: Positron emission tomography is employed in adults for the evaluation of myocardial perfusion and the detection of myocardial viability. METHODS: Perfusion and metabolism findings on PET in infants and children with suspected coronary abnormalities (age 14 days to 12 years old, mean 3.3 +/- 4.0 years) were correlated with findings on coronary angiography, echocardiography, and myocardial histopathology. The segmental myocardial uptake of the flow tracer (13)N-ammonia and of the glucose tracer (18)F-deoxyglucose ((18)FDG) was graded on a five-point scale and compared with the angiographic perfusion score, with regional wall motion, and the presence of fibrosis. RESULTS: There was an agreement of r = 0.72 (p < 0.05) between regional myocardial perfusion and angiography. The correlation of histopathologic changes with normal, moderately, and severely reduced segmental (13)N-ammonia uptake was 87%, 60%, and 75%, respectively. Segmental myocardial (18)FDG uptake and histopathologic findings were concordant in 48 (79%) of 64 segments without fibrosis; absence of viability by perfusion and metabolism imaging correlated with the presence of fibrosis in 21 (84%) of 25 segments. CONCLUSIONS: The observed agreements between the findings on PET perfusion and metabolism imaging with those on coronary angiography, echocardiography, and histopathology support the utility and accuracy of PET for characterizing myocardial perfusion abnormalities and viability in pediatric patients.     

Properties of an ideal PET perfusion tracer: new PET tracer cases and data

An ideal positron emission tomography (PET) tracer should be highly extractable by the myocardium and able to provide high-resolution images, should enable quantification of absolute myocardial blood flow (MBF), should be compatible with both pharmacologically induced and exercise-induced stress imaging, and should not require an on-site cyclotron. The PET radionuclides nitrogen-13 ammonia and oxygen-15 water require an on-site cyclotron. Rubidium-82 may be available locally due to the generator source, but greater utilization is limited because of its relatively low myocardial extraction fraction, long positron range, and generator cost. Flurpiridaz F 18, a novel PET tracer in development, has a high-extraction fraction, short positron range, and relatively long half-life (as compared to currently available tracers), and may be produced at regional cyclotrons. Results of early clinical trials suggest that both pharmacologically and exercise-induced stress PET imaging protocols can be completed more rapidly and with lower patient radiation exposure than with single-photon emission computerized tomography (SPECT) tracers. As compared to SPECT images in the same patients, flurpiridaz F 18 PET images showed better defect contrast. Flurpiridaz F 18 is a potentially promising tracer for assessment of myocardial perfusion, measurement of absolute MBF, calculation of coronary flow reserves, and assessment of cardiac function at the peak of the stress response.     

Positron emission tomography of the heart

Positron emission computed tomography (PET) has introduced a new dimension into cardiology by its ability of imaging in-vivo cardiac metabolism non-invasively. Following administration of labelled substrates PET provides display of digitized heart tomograms, which reflect tracer concentration quantitatively. Thus, regional myocardial metabolism and perfusion can be measured using appropriate tracers such as C-11 palmitate, F-18 deoxyglucose, N-13 or C-11 amino acids, N-13 ammonia and Rb-82. Accordingly, the documentation of marked metabolic derangements during ischemia and infarction by initial clinical PET studies have been very promising diagnostically. It has been shown that normal, resting ischemic and acutely ischemic and infarcted tissue can be differentiated reliably. In cardiomyopathies, disturbed energy substrate utilization not known until then was found by means of PET. Unfortunately, PET will be available only in larger centers in the near future because of its high cost.     

Assessment of alphavbeta3 integrin expression after myocardial infarction by positron emission tomography

AIMS: The purpose of this study was to determine the feasibility of a new positron emission tomography (PET) imaging approach using an (18)F-labelled alpha(v)beta(3) integrin antagonist ((18)F-Galacto-RGD) to monitor the integrin expression after myocardial infarction. METHODS AND RESULTS: Male Wister rats were subjected to 20 min transient left coronary artery occlusion followed by reperfusion. Autoradiographic analysis and in vivo PET imaging were used to determine myocardial (18)F-Galacto-RGD uptake at different time points following reperfusion. RESULTS: PET imaging and autoradiography demonstrated no significant focal myocardial (18)F-Galacto-RGD uptake in non-operated control rats and at day 1 after reperfusion. However, focal accumulation in the infarct area started at day 3 (uptake ratio = 1.91 +/- 0.22 vs. remote myocardium), peaked between 1 (3.43 +/- 0.57) and 3 weeks (3.43 +/- 0.95), and decreased to 1.96 +/- 0.40 at 6 months after reperfusion. Pretreatment with alpha(v)beta(3) integrin antagonist c(-RGDfV-) significantly decreased tracer uptake, indicating the specificity of tracer uptake. The time course of focal tracer uptake paralleled vascular density as measured by CD31 immunohistochemical analysis. CONCLUSION: Regional (18)F-Galacto-RGD accumulation suggests up-regulation of alpha(v)beta(3) integrin expression after myocardial infarction, which peaks between 1 and 3 weeks and remains detectable until 6 months after reperfusion. This new PET tracer is promising for the monitoring of myocardial repair processes.     

Positron emission tomography

Positron emission tomography (PET) is currently the most sophisticated scintigraphic imaging technique developed for in-vivo quantification of cardiac physiology and biochemistry. The state-of-the-art PET technology allows delineation of regional tracer activity with high spatial and temporal resolution. A large number of radiopharmaceuticals have been developed to study myocardial perfusion enabling accurate diagnosis and localization of coronary artery disease (CAD) and energy metabolism. More recently, newer tracers such as radiolabeled catecholamine analogues allow the pre- and postsynaptic evaluation of cardiac autonomic innervation. Metabolic imaging with PET represents currently the gold standard for tissue viability assessment with well-validated diagnostic and prognostic information. F-18 deoxyglucose has been also used in combination with SPECT or coincidence imaging providing comparable clinical information but without need for the expensive and rarely available imaging technology of PET. The assessment of coronary flow reserve is the most sensitive scintigraphic method to i) detect vascular abnormalities before their hemodynamic significance, ii) diagnose and define the extent of CAD, and iii) to monitor the effects of (non)pharmacological intervention on regional and global cardiac flow. C-11 hydroxyephedrine (HED) allows imaging of sympathetic neuronal function. the course of cardiac reinnervation after cardiac transplantation was demonstrated with C-11 HED PET, and preliminary evidence suggests that this technique might provide prognostic information on sympathetic neuronal status in congestive heart failure, too. The functional and prognostic relevance of PET imaging together with the increased availability of lower cost instrumentation imaging will define its future role in the diagnosis, assessment of extent, prognosis and in the therapeutic decision making of cardiac disease.     

Microvascular Angina: Assessment of Coronary Blood Flow,Flow Reserve,and Metabolism

Microvascular angina (MVA) is an often overlooked cause of significant chest pain. Decreased myocardial perfusion secondary to dysregulated blood flow in the microvasculature can occur in the presence or absence of obstructive epicardial coronary artery disease. The corresponding myocardial ischemia and angina is now a well-established diagnosis, made by detection of decreased coronary flow reserve (CFR). Although low CFR and MVA are associated with poor prognosis, there is initial evidence for reversibility of this abnormal vascular regulation with aggressive medical therapy and control of associated risk factors. Current assessment of MVA is carried out predominantly during cardiac catheterization; however, noninvasive techniques to assess CFR are being developed, including PET, MRI, and CT modalities. Quantitative tracer techniques or imaging of metabolic disturbances reflecting ischemia will likely enhance diagnostic approaches for such patients as well as allow more frequent monitoring of response to therapy.     

Imaging cardiac neuronal function and dysfunction

In recent years, the importance of alterations of cardiac autonomic nerve function in the pathophysiology of heart diseases including heart failure, arrhythmia, ischemic heart disease, and diabetes has been increasingly recognized. Several radiolabeled compounds have been synthesized for noninvasive imaging, including single photon emission CT and positron emission tomography (PET). The catecholamine analogue I-123 metaiodobenzylguanidine (MIBG) is the most commonly used tracer for mapping of myocardial presynaptic sympathetic innervation on a broad clinical basis. In addition, radiolabeled catecholamines and catecholamine analogues are available for PET imaging, which allows absolute quantification and tracer kinetics modeling. Postsynaptic receptor PET imaging added new insights into mechanisms of heart disease. These advanced imaging techniques provide noninvasive, repeatable in vivo information of autonomic nerve function in the human heart and are promising for providing profound insights into molecular pathophysiology, monitoring of treatment, and determination of individual outcome.     

Detection of Viability of Dysfunctional Myocardium in Coronary Heart Disease. I. Radionuclide Imaging

The question of myocardial viability in the presence of severe regional or global left ventricular dysfunction in patients with coronary artery disease poses a formidable challenge to the clinician. If the dysfunctional myocardium is viable, revascularization procedures are associated with improved contractile function, whereas no benefits are expected if the myocardium is nonviable. Thus, assessment of myocardial viability is necessary before optimal decisions can be made regarding the use of bypass surgery, angioplasty, or cardiac transplantation in a timely and cost-effective manner. The most reliable methods to detect viable myocardium include myocardial metabolic imaging of exogenous glucose utilization using ⊃18 F-FDG in combination with myocardial perfusion/flow studies, assessment of the integrity of the oxidative metabolism using ⊃11 C-acetate, and measurement of regional blood flow using ⊃13 N-ammonia or ⊃15 O-water. However, the equipment and expertise necessary to perform positron emission tomography (PET) are expensive and not generally available. Fortunately, alternative imaging modalities using routine radionuclide and echocardiographic techniques are widely available and have nearly the same accuracy as PET metabolic imaging. Excellent alternatives include perfusion imaging with ⊃201 thallium using the stress-redistribution-reinjection or the rest-redistribution protocols, or ⊃99m technetium sestamibi using a rest-delayed imaging protocol. As old techniques are being refined and new methods developed, such as metabolic imaging using SPECT techniques that utilize ⊃18 F-FDG or fatty acids labeled with ⊃131 I, the challenge is to choose the most appropriate technique after a critical review of the institutional resources and the merits and weaknesses of the technique. This revised version was published online in July 2006 with corrections to the Cover Date.     

Recent advances in cardiac positron emission tomography in the clinical management of the cardiac patient

Despite being primarily a research tool, positron emission tomography (PET) has seen slow but steady growth in the clinical management of the cardiac patient. The two major clinical applications of cardiac PET are regional myocardial perfusion imaging to determine the presence and severity of coronary artery disease and metabolic imaging to differentiate viable from nonviable myocardium in patients with ischemic left ventricular dysfunction. Indeed, PET with either nitrogen 13 ammonia or rubidium 82 may offer advantages over current single photon emission computed tomography approaches to assess myocardial perfusion. PETwith fluorine 18 fluorodeoxyglucose is considered the current gold standard for identifying viable myocardium. Finally, the use of PET to quantify myocardial perfusion, metabolism, and innervation has led to key insights into the role of altered microvascular function, substrate metabolism, and neuronal function in a variety of cardiac disease processes.     

Positron emission tomography in ischemic heart disease

Non-invasive assessment of ischemic heart disease remains a challenging task, even with a large armory of diagnostic modalities. Positron emission tomography (PET) is an advanced radionuclide technique that has been available for decades. Originally used as a research tool that contributed to advances in the understanding of cardiovascular pathophysiology, it is now becoming established in clinical practice and is increasingly used in the diagnosis and risk stratification of patients with ischemic heart disease. PET myocardial perfusion imaging has a mean sensitivity and specificity of around 90% for the detection of angiographically significant coronary artery disease, and is also highly accurate for assessing the prognosis of patients with ischemic heart disease. Depending on the radiotracer used, it can provide information not only on myocardial perfusion but also on myocardial metabolism, which is essential for viability assessment. The potential of this imaging technique has been further increased with the introduction of hybrid scanners, which combine PET with computed tomography or cardiac magnetic resonance imaging, offering integrated morphological and functional information and hence comprehensive assessment of the effects of atherosclerosis on the myocardium. The scope of this review is to summarize the role of PET in ischemic heart disease.     

Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.     

Untersuchung der Myokardperfusion mit der Positronen-Emissions-Tomographie

Positron emission tomography (PET) of the heart has gained widespread scientific and clinical acceptance with regard to two indications: 1) The detection of perfusion abnormalities by qualitative and semiquantitative analyses of perfusion images at rest and during physical or pharmacological stress using well-validated perfusion tracers, such as N-13 ammonia, Rb-82 rubidium chloride, or O-15 labeled water. 2) Viability imaging of myocardial regions with reduced contractility by combining perfusion measurements with substrate metabolism as assessed from F-18 deoxyglucose utilization. This overview summarizes the use of PET as a perfusion imaging method. With a sensitivity > 90% in combination with high specificity, PET is today the best-validated available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. The high diagnostic accuracy and the methological advantages as compared to conventional scintigraphy allows one to use PET perfusion imaging to detect subtle changes in the perfusion reserve for the detection of CAD in high risk but asymptomatic patients as well as in patients with proven CAD undergoing various treatment forms such as risk factor reduction or coronary revascularization. In patients following orthotopic heart transplantation, evolving transplant vasculopathy can be detected at an early stage. Quantitative PET imaging at rest allows for detection of myocardial viability since cellular survival is based on maintenance of a minimal perfusion and structural changes correlate to the degree of perfusion reduction. Furthermore, quantitative assessment of the myocardial perfusion reserve detects the magnitude and competence of collaterals in regions with occluded epicardial collaterals and, thus, imaging of several coronary distribution territories in one noninvasive study. The cost of PET in combination with the cost of a cyclotron facility together with the demanding methological problems have limited the availability of perfusion PET to a few sophisticated centers. Therefore, quantitative PET investigations of myocardial perfusion have been performed predominantly for scientific purposes, and the cost-effectiveness of PET in the everyday clinical setting is not yet finally proven. However, the unique possibilities of PET to study non-invasively and quantitatively myocardial perfusion and metabolism as well as cardiac innervation and pharmacokinetics of cardiac drugs have established cardiac PET as a scientific tool of the highest quality for the future.     

Advances in rubidium PET and integrated imaging with CT angiography

The role of rubidium-82 (Rb-82) positron emission tomography (PET) in the evaluation and care of patients with suspected coronary artery disease is evolving in conjunction with advances in PET instrumentation, data analysis, and clinical research. Instrumentation developments such as three-dimensional acquisition, new scintillator materials, and x-ray CT help to improve the quality of Rb-82 images. New approaches to kinetic modeling and software tools for analysis of clinical Rb-82 studies are being developed and evaluated, enabling quantification of absolute myocardial blood flow and flow reserve. Recent clinical research studies are providing new insights into the value of Rb-82 cardiac imaging compared with single photon emission CT myocardial perfusion imaging. Integrated x-ray CT angiography and Rb-82 PET perfusion imaging on hybrid PET/CT systems is an exciting new prospect. Complementary anatomical and functional information on atherosclerosis and ischemia can be provided in a single imaging session for better diagnosis and risk stratification of patients with coronary artery disease.     

Positron Emission Tomography in Acute Coronary Syndromes

Several imaging techniques have been used to assess cardiac structure and function, to understand pathophysiology, and to guide clinical decision making in the setting of acute coronary syndromes (ACS). Over the last years, cardiac positron emission tomography (PET) has affirmed its role in this setting. Indeed, the combined quantitative assessment of myocardial metabolism and perfusion has allowed to better understand the functional status of infarcted and non-infarcted myocardium, thus improving our knowledge of myocardial response to necrosis. More recently, several studies, taking advantage of previous observations in patients with cancer, have shown that PET could also provide important information on the mechanisms of vascular instability through the early identification of activated inflammatory cells in the atherosclerotic plaque. These findings are opening the way to more effective forms of prevention of acute vascular syndromes in high-risk patients; furthermore, new more sensitive and specific tracers for the identification of vascular inflammation are under development. In this review, we describe the potential and limitations of PET in the assessment of ACS.     

The noninvasive assessment of myocardial viability

The major objective of noninvasive imaging for detection of myocardial viability is to assist in the improved selection of patients with coronary artery disease and severe left ventricular dysfunction who would benefit most from revascularization. The techniques most commonly used to identify viable myocardium are thallium-201 (TI) scintigraphy, positron emission tomography (PET) using a flow tracer in combination with a metabolic tracer, technetium-99m (Tc) sestamibi imaging, and dobutamine echocardiography. On stress TI scintigraphy, asynergic regions showing normal thallium uptake, an initial defect with delayed redistribution at 3–4 h, late redistribution at 24 h, or defect reversibility after reinjection of a second dose of TI at rest all suggest preserved viability. The greater the final uptake of TI in areas of regional myocardial dysfunction preoperatively, the greater the improvement in ejection fraction after coronary revascularization. Demonstration of uptake of fluoro-18 deoxyglucose (FDG) in regions of diminished blood flow on PET imaging also correlates well with improved systolic function after revascularization. Tc sestamibi may also be useful for assessment of myocardial viability, particularly after thrombolytic therapy for acute myocardial infarction. Dobutamine echocardiography has good positive predictive value for viability determination, but absence of systolic thickening in an akinetic zone in response to intravenous infusion of the drug may still be associated with viable myocardium in 25–50% of segments. Of all the techniques cited above, quantitative resting TI scintigraphy may be the best approach for distinguishing between viable and irreversibly injured myocardium.     

Positron Emission Tomography in oncology: Present and future of PET and PET/CT

PET is a crucial technique in molecular imaging, allowing in vivo assessment and localization of pathological processes, thanks to its ability to detect very small amounts of radioactive molecules. This is of particular interest in oncology where abnormal metabolism or synthesis in tumor cells but also various tumor characteristics can be studied using this nuclear medicine technique. FDG is currently the most widely used tracer, nowadays essential in the management of various malignancies, with large applications in diagnosis, initial assessment, therapy monitoring, and recurrence detection. The combination of anatomical information provided by PET/CT further increased its interest. Beyond its spread use in daily practice, future applications of PET will involve other tracers than FDG and develop research applications in humans as well as in small animals.     

The Influence of Insulin Resistance,Obesity, and Diabetes Mellitus on Vascular Tone and Myocardial Blood Flow

Among individuals with cardiovascular risk factors, reductions in coronary vasodilator capacity with or without diabetes mellitus (DM) carry important diagnostic and prognostic information. Positron emission tomography (PET) myocardial perfusion imaging in concert with tracer kinetic modeling allows the assessment of absolute regional myocardial blood flow (MBF) at rest and its response to various forms of vasomotor stress. Such noninvasive evaluation of myocardial flow reserve (MFR) or the vasodilator capacity of the coronary circulation expands the possibilities of conventional scintigraphic myocardial perfusion imaging from identifying flow-limiting epicardial coronary artery lesions to understanding the underlying pathophysiology of diabetic vasculopathy, microcirculatory dysfunction, and its atherothrombotic sequelae. Invaluable mechanistic insights were recently reported with PET by unraveling important effects of insulin resistance, obesity, and DM on the function of the coronary circulation. Such noninvasive assessment of coronary circulatory dysfunction enables monitoring its response to antidiabetic medication and/or behavioral interventions related to weight, diet, and physical activity that may evolve as a promising tool for an image-guided and personalized preventive diabetic vascular care. Whether PET-guided improvement or normalization of hyperemic MBF and/or MFR will translate into improved patient outcome in DM is a laudable goal to pursue next.