Positron emission tomography in coronary artery disease

PURPOSE OF REVIEW: Mortality and coronary events are dramatically reduced in coronary artery disease by intense lifestyle and pharmacologic management without further improvement by revascularization procedures, thereby requiring definitive noninvasive diagnostic imaging. Consequently, this review summarizes the evidence supporting cardiac positron emission tomography as a definitive, noninvasive, 'one-stop' test for routine management of coronary artery disease that is well validated in the scientific literature and illustrated by clinical cases. RECENT FINDINGS: Substantial evidence documents accuracy of positron emission tomography for identifying early or advanced coronary artery disease, quantifying its severity, risk stratification, deciding on revascularization procedures, following progression or regression and for evaluating coronary endothelial function as the basis for preventive treatment. Recent technology like positron emission tomography-computed tomography, however, requires advanced knowledge, training and attention to technical details to avoid common artifactual results and to provide definitive conclusions illustrated in this review. SUMMARY: Cardiac positron emission tomography, done correctly with attention to technical details, provides definitive noninvasive assessment of early or advanced coronary atherosclerosis as the basis for invasive procedures or for lifelong intense risk factor management, demonstrates progression or regression of disease, predicts clinical outcomes and serves as the primary definitive noninvasive guide for managing coronary artery disease.     

Positron emission tomography

Positron emission tomography and tracers of blood flow and of metabolism offer a most unique capability: The noninvasive study of regional myocardial metabolism and its derangements as a result of regional or global myocardial disease. Research with PET not only has confirmed the existence of metabolic fluxes and reactions as established previously through highly invasive or even destructive investigational techniques but has provided new insights into pathophysiologic processes, especially in ischemic and post-ischemic myocardium. From these investigations in both animal experiments and in humans, observations have emerged which indicate a place for PET in clinical cardiology. PET is likely to contribute to detection of disease, to characterizing its extent and severity as well as to decide upon the most appropriate therapeutic strategy and assessing its results. It is recognized that many of these observations with clinical implications await confirmation through larger clinical trials, follow-up studies as well as independent confirmation. Besides exploring ischemic heart disease, PET is equally suitable for examining substrate fluxes and interactions in other disorders as for example in intrinsic myocardial disease like primary and secondary cardiomyopathies. While derangements of metabolism in these disorders may be an expression of the consequences of the disease process or its underlying mechanisms itself, findings on PET will allow formulation of new hypotheses on disease mechanisms that conversely can then be tested. In addition to F-18 2-deoxyglucose and C-11 palmitate, the number of tracers for substrate metabolism is likely to increase. An example is C-11 acetate currently intensely investigated as a tool for measuring overall myocardial oxidative metabolism. Others as for example C-11 labeled short chain fatty acids are on the horizon. The study of cardiac receptors is similarly possible. Thus, a set of tools will soon be available for dissection of entire metabolic pathways and for determination of rate limiting steps in health and disease and to more clearly define specific defects in biochemical reaction steps that critically contribute to or even ae the specific cause of disease.     

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.     

Positron emission tomography and the changing paradigm in coronary artery disease

Summary While lowering cholesterol with HMG-CoA reductase inhibitors appears to affect little if at all the severity of coronary artery stenoses, at least over the time periods studied, it markedly reduces cardiac morbidity and mortality. The beneficial effects of these agents have therefore been attributed to plaque stabilization and improved coronary vasomotor function. This then has shifted the emphasis of detection and treatment of coronary artery disease from the assessment of structural to functional alterations. With PET based measurements of regional myocardial blood flow, the function of the coronary circulation in humans can now be evaluated non-invasively. Multiple studies with this approach reported diminished hyperemic flow responses in patients without hemodynamically significant coronary stenoses but with coronary risk factors. Furthermore, lipid lowering with HMG-CoA reductase inhibitors was consistently found to enhance hyperemic flow responses to pharmacologic vasodilation as an index of the integrated function of the human coronary circulation. Recent studies with PET based measurements of blood flow target specifically the endothelial dependent coronary vasomotion and revealed abnormalities in chronic smokers and in postmenopausal women, that is, after estrogen withdrawal. Conversely, L-arginine supplementation in smokers and hormone replacement therapy in post-menopausal women without coronary risk factors normalized endothelial dependent flow responses. These observations suggest that endothelial dysfunction as a pivotal event early in the development of coronary atherosclerosis can be identified noninvasively with PET which will also be useful for measuring responses to lifestyle modification and pharmacologic treatment for improving coronary circulatory function.     

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.     

Positron emission tomography in the lung

Positron emission tomography using the ECAT II scanner to image and measure regional lung function is outlined. The combined use of transmission and emission imaging provides quantitative information about regional lung structure (density, extravascular density, and vascular volume) and function (ventilation, perfusion, ventilation-perfusion ratios, glucose metabolic rate). Clinical applications in asthma, chronic obstructive lung disease, pulmonary vascular disease, interstitial lung disease, and squamous cell carcinoma are presented. Future prospects for PET are discussed.     

Positron emission tomography imaging in the thorax

Positron emission tomography imaging has proven valuable in the evaluation and management of thoracic abnormalities. It is more accurate than CT or MR imaging in characterizing indeterminate focal abnormal pulmonary opacities, staging lung cancer, and assessing the therapeutic response. PET imaging in lung cancer also appears to be cost-effective, particularly with whole-body studies. The metabolic and physiologic abnormalities used in FDG-PET imaging, rather than conventional anatomic or morphologic characteristics, provide an invaluable model for the future of tumor imaging.     

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.     

Positron emission tomography and interventional cardiology

Current noninvasive diagnostic techniques have limited accuracy for detection of coronary artery disease (CAD) in symptomatic and (particularly) asymptomatic patients with silent disease. Furthermore, no standard noninvasive method provides reliable diagnostic information on the location of the coronary arteries involved, the severity of stenosis, the presence of collaterals and myocardial viability. Based on greater than 1,000 cardiac studies at the University of Texas, cardiac positron emission tomography (PET) with either generator-produced rubidium-82, cyclotron-produced N-13 ammonia, or F-18 deoxyglucose is suitable for 4 routine diagnostic purposes: (1) noninvasive diagnosis of CAD in either symptomatic or asymptomatic subjects with a sensitivity of 95 to 98% and specificity of 95 to 100%. This accuracy is now sufficient to schedule diagnostic catheterization and multivessel angioplasty with surgical backup on the basis of the PET scan. At the University of Texas we carry out PET in asymptomatic and symptomatic patients to direct those with mild disease to cholesterol-lowering reversal therapy and those with severe disease to percutaneous transluminal coronary angioplasty (PTCA); (2) assessment of physiologic severity of coronary artery stenosis as compared to automated quantitative coronary arteriographic analysis. Changes in stenosis severity are followed before and after interventions including PTCA, bypass surgery, vasodilator drugs and cholesterol control regimens for reversal of coronary atherosclerosis; (3) imaging myocardial infarction, ischemia, viability, zone at risk and sizing of these pathophysiologic processes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Positron emission tomography in clinical cardiology

Positron emission tomography of the heart is a physiologic imaging technique that enables both qualitative and quantitative assessment of regional myocardial blood flow and substrate utilization. Exercise or dipyridamole perfusion imaging with PET is both sensitive and specific for detecting coronary disease and may prove clinically useful in assessing the physiologic significance of anatomically defined stenoses and for noninvasively following stenosis progression or regression. PET can be used to localize and quantitate the extent of antecedent myocardial infarction, and frequently identifies viable tissue when routinely utilized clinical tests indicate completed infarction. The tissue characterization afforded by metabolic imaging with PET in coronary heart disease allows non-invasive identification of viable but jeopardized tissue in a variety of clinical ischemic syndromes, thereby permitting the cardiologist to intervene in anticipation of myocardial salvage. As future developments in PET imaging occur, our understanding of the basic biochemical abnormalities characterizing myocardial ischemia will be utilized with increasing frequency to improve the clinical care provided to patients with coronary heart disease.     

Positron emission tomography in neuroendocrine tumours

Positron emission tomography is an in vivo tracer and imaging technique that utilizes short-lived positron emitting radionuclides (11C, 15O, 13N, 18F) with half-lives ranging between 2 min and 2 hours. These radionuclides are interesting from the labelling viewpoint since they are natural constituents of most biologically active compounds. The short half-life is an advantage with regard to the irradiation dose to the patient but it is also a limitation since it requires the production of these radionuclides in close vicinity to the positron emission tomography camera.     

Positron emission tomography in pulmonary edema

Positron emission tomography (PET) enables the concentration of positron-emitting isotopes to be measured quantitatively in vivo. It is also possible to measure the physical density of the lung with an external source of radiation. Several investigative procedures have been described for studying the distribution of the intravascular and extravascular water pools in the lung with PET. Clinical applications of these procedures have shown that acute hydrostatic pulmonary edema in humans has characteristics similar to experimentally induced hydrostatic edema. In chronic interstitial pulmonary edema, on the other hand, the relationship between the intravascular and extravascular water pools is different, and experimental models of acute pulmonary edema may not be relevant to this category of patients. The possible effects of these differences on lung function, such as gas exchange, may be studied with PET in the future. Microvascular permeability to proteins may also be studied.     

Positron emission tomography in esophageal cancer

Positron emission tomography (PET), a functional imaging modality, has provided the transition between the research environment and the clinical environment over the last 10 years. Its primary use is in the field of oncology, where it is being increasingly used in the management of several tumor types including esophageal cancer. ¹⁸F-Fluorodeoxyglucose PET (FDG-PET) scans may also be used to distinguish between benign and malignant tumors, to identify different stages of tumor spread, to assess for tumor recurrence, and monitor the response to therapy of malignant diseases. This review aims to outline the current and future roles of PET scanning in the field of esophageal cancer.