Cardiovascular nuclear medicine imaging techniques are part of the ever-growing clinical noninvasive imaging armamentarium for the evaluation of suspected or known coronary artery disease (CAD). These techniques provide valuable information regarding diagnosis and clinical risk, and consequently have established a role in the management of this disease. In this chapter, we will provide a concise summary of contemporary nuclear cardiology techniques, and then use a case-based approach to illustrate their practical utility in the evaluation and management of patients after myocardial infarction (MI). The role of nuclear cardiology techniques in the initial assessment of patients with chest pain suspicious for MI is discussed in Chapter 9 . The use of echocardiography and use of cardiac magnetic resonance imaging (MRI) after MI are addressed in Chapter 31 and Chapter 33 , respectively.
Technical Considerations for Radionuclide Imaging
Fundamentals of Single Photon Emission Computed Tomography and Positron Emission Tomography Imaging
Radionuclide imaging techniques are commonly used for the evaluation of patients with known or suspected CAD, including those presenting with acute coronary syndromes (ACS). These techniques use radiolabeled drugs, or radiopharmaceuticals ( Table 32-1 ), which are injected intravenously and trapped in myocardial tissue. Radioactivity within the heart decays by emitting gamma rays. The interaction between these gamma rays and the detectors in specialized scanners—single photon emission computed tomography (SPECT) and positron emission tomography (PET)—creates a scintillation event or light output, which can be captured by digital recording equipment to form an image of the heart. Like computed tomography (CT) (see Chapter 9 ) and MRI (see Chapter 33 ), radionuclide imaging also can generate tomographic (three-dimensional) views of the heart.
|Radiopharmaceutical||Imaging Technique||Physical Half-life||Application|
|99m Tc agents (sestamibi, tetrofosmin)||SPECT||6 hours||Myocardial perfusion and viability imaging|
|201 Tl||SPECT||72 hours||Myocardial perfusion and viability imaging|
|123 I-mIBG||SPECT||13 hours||Cardiac sympathetic neuronal imaging|
|82 Rb||PET||76 seconds||Myocardial perfusion imaging|
|13 N-ammonia||PET||10 minutes||Myocardial perfusion imaging|
|18 F-FDG||PET||120 minutes||Myocardial viability imaging|
Protocols for Myocardial Perfusion and Viability Imaging
Imaging protocols are tailored to the individual patient based on the clinical question and on patient-specific risk, ability to exercise, and body mass index, among other factors. Electrocardiogram (ECG)-triggered gated rest and stress images are acquired after intravenous injection of the radiopharmaceutical and used to define the extent and severity of myocardial ischemia and scar, as well as regional and global cardiac function and remodeling. The choice between exercise versus pharmacologic stress with vasodilators (adenosine, dipyridamole, or regadenoson) and direct chronotropic/inotropic stimulation with dobutamine is based on well-defined guidelines depending on the patient’s condition, the clinical question, and safety considerations, especially in the post-MI patient (see Chapter 30 ).
For SPECT imaging, technetium-99m ( 99m Tc)-labeled tracers are the most commonly used imaging agents because they are associated with the best image quality and the lowest radiation dose to the patient. After intravenous injection, myocardial uptake of 99m Tc-labeled tracers is rapid (1 to 2 minutes). After uptake, these tracers become trapped intracellularly in mitochondria and show minimal change over time. Because of these kinetics, 99m Tc tracers can be helpful in the investigation of chest pain occurring at rest, in that the tracer can be injected while the patient is having chest pain and images obtained some time later after symptoms subside (within 6 hours after injection). Because the radiotracer is trapped at the time of injection, the images provide a snapshot of myocardial perfusion at that moment, even if the acquisition was delayed. This property is a key requirement for the use of 99m Tc SPECT in the quantification of myocardium at risk and salvage in patients with acute MI (see later under Quantification of Myocardium at Risk, Infarct Size, and Myocardial Salvage ). Indeed, a normal myocardial perfusion study after a rest injection in a patient with active chest pain effectively excludes myocardial ischemia as the cause of chest pain (high negative predictive value) (see Chapter 9 ). Although commonly used in the past for perfusion imaging, thallium-201 ( 201 Tl) protocols are now rarely used because they are associated with a higher radiation dose to the patient.
PET myocardial perfusion imaging is an alternative to SPECT and is associated with improved diagnostic accuracy and lower radiation dose to the patient, owing to the fact that radiotracers typically are short-lived ( Table 32-1 ). The ultrashort half-life of some PET radiopharmaceuticals in clinical use, such as rubidium-82 ( 82 Rb), is the primary reason that PET imaging generally is combined with pharmacologic stress, as opposed to exercise, because pharmacologic stress allows for faster imaging of these rapidly decaying tracers. However, use of exercise is possible with relatively longer-lived radiotracers (e.g., 13 N-ammonia). For myocardial perfusion imaging, 82 Rb does not require an onsite medical cyclotron (it is available from a strontium-82 [ 82 Sr]/ 82 Rb generator), so it is the most commonly used radiopharmaceutical. 13 N-ammonia has better flow characteristics (higher myocardial extraction) and imaging properties than 82 Rb, but use of this agent does require access to a medical cyclotron. In comparison with SPECT, PET gives improved spatial and contrast resolution, and it provides absolute measures of myocardial perfusion (in mL/min/g of tissue), thereby providing a quantitative measure of regional and global coronary flow reserve. As discussed later on, quantitative measures of myocardial blood flow and flow reserve help improve diagnostic accuracy and risk stratification.
Contemporary PET and SPECT scanners frequently are combined with a CT scanner, for so-called hybrid PET-CT and SPECT-CT. CT is used primarily to guide patient positioning in the field of view and for correcting inhomogeneities in radiotracer distribution from attenuation by soft tissues (so-called attenuation correction). However, it also can be used to obtain diagnostic data including coronary artery calcium score and/or CT coronary angiography (see Chapter 9 ), although the usefulness of combined studies in the post-MI patient is more limited.
For the evaluation of myocardial viability in patients after MI, myocardial perfusion imaging with SPECT or PET usually is combined with metabolic imaging—specifically, 18 F-fluorodeoxyglucose (FDG) PET. In hospital settings lacking access to PET scanning, 201 Tl SPECT imaging is a useful alternative.
Evaluation of Myocardial Ischemia, Viability, and Function
The presence of a reversible myocardial perfusion defect is indicative of ischemia ( Figure 32-1 , top), whereas a fixed perfusion defect generally reflects scarred myocardium from previous infarction ( Figure 32-1 , bottom). Regional myocardial perfusion usually is assessed by semiquantitative visual analysis of the rest and stress images. The regional scores are then summed into global scores that reflect the total burden of ischemia and scar in the left ventricle. Objective quantitative image analysis is a helpful tool for a more accurate and reproducible estimation of total defect size and severity and generally is used in combination with semiquantitative visual analysis. The semiquantitative and quantitative scores for ischemia and scar are linearly related to the risk of adverse cardiovascular events and are most useful in guiding patient management, especially the need for revascularization, and for assessing response to medical therapy.
Quantification of Myocardial Ischemia and Viability
Myocardial perfusion and metabolic imaging are commonly used to evaluate the patient after MI, especially when the question of revascularization is being considered. The protocols are tailored to the clinical question and provide important quantitative information: (1) myocardial infarct size; (2) extent of stunning and hibernating myocardium; (3) magnitude of inducible myocardial ischemia within the infarct-related territory and in remote myocardium, the latter reflecting multivessel CAD; and (4) left ventricular function and volumes.
Both 201 Tl-labeled and, especially, 99m Tc-labeled agents provide accurate and reproducible measurements of regional and global myocardial infarct size ( Figure 32-2 ). The use of metabolic imaging with PET has been extensively validated and is commonly used for assessing myocardial viability. 18 F-FDG is used to assess regional myocardial glucose utilization (an index of tissue viability) and compared to perfusion images to define metabolic abnormalities associated with infarction and hibernation. Myocardial regions showing reduced perfusion and increased FDG uptake at rest (so-called perfusion-FDG mismatch ) identify areas of viable but hibernating myocardium, whereas regions showing reduced perfusion and reduced FDG uptake at rest (so-called perfusion-FDG match ) are consistent with myocardial scar ( Figure 32-3 ). These metabolic patterns have important implications for selection of patients for revascularization (see later under Evaluation of Patients with Heart Failure after Myocardial Infarction ).
Quantification of Myocardial Blood Flow and Coronary Flow Reserve
Myocardial blood flow (in mL/min/g of myocardium) and coronary flow reserve (CFR)—defined as the ratio between peak stress and rest myocardial blood flow)—are important physiologic parameters that can be measured by routine postprocessing of myocardial perfusion PET images. These absolute measurements of tissue perfusion are accurate and reproducible. Pathophysiologically, CFR estimates provide a measure of the integrated effects of epicardial coronary stenoses, diffuse atherosclerosis and vessel remodeling, and microvascular dysfunction on myocardial perfusion; accordingly, the value obtained is a more sensitive measure of myocardial ischemia. In the setting of increased oxygen demand, a reduced CFR can upset the supply-demand relationship and lead to myocardial ischemia, subclinical left ventricular dysfunction (diastolic and systolic), symptoms, and death. One of the practical applications of CFR measurements is in the evaluation of flow-limiting stenosis, especially useful in the context of multivessel CAD ( Figure 32-4 ). Indeed, a relatively normal CFR (above 1.9) virtually excludes the possibility of significant stenosis.
Furthermore, consistent evidence indicates that CFR measurements by PET can identify subgroups of patients with different clinical risk across a wide spectrum of ischemic burden ( Figure 32-5 ). Indeed, the presence of relatively preserved CFR identifies patients with CAD at a significantly lower risk for cardiac death, regardless of the semiquantitative extent of stress-induced ischemia. Conversely, a reduced CFR identifies patients at significantly higher risk for cardiac death, even among those in whom the semiquantitative extent of ischemia is mild to moderate. These data suggest that the traditional (semiquantitative) measures of ischemia alone may be insufficient to identify potential prognostic benefit from myocardial revascularization.
Quantification of Myocardium at Risk, Infarct Size, and Myocardial Salvage
Radionuclide imaging has been extensively validated and used to quantify myocardium at risk, infarct size, and myocardial salvage after reperfusion therapy for acute MI. Both 201 Tl and 99m Tc agents have been used for this purpose. However, 99m Tc agents have been the most widely used and validated. The fact that after intravenous injection and initial myocardial uptake, tissue retention of 99m Tc agents remains relatively constant is especially important in the setting of acute MI. Consequently, these agents can be injected intravenously when a patient with acute MI first presents to the emergency department. Imaging can be delayed while the patient undergoes acute care and still reflect myocardial tissue perfusion at the time of initial presentation (i.e., myocardium at risk). Final infarct size is then assessed by a second injection of 99m Tc agents and imaging 5 to 7 days after reperfusion therapy. The quantitative difference between the total perfusion defect size in the initial and late images reflects myocardial salvage ( Figure 32-6 ). This protocol has been widely used in clinical trials evaluating the effect of therapies designed to limit infarct size. FDG PET also provides accurate quantification of infarct size. Clinically, the measurement of infarct size with radionuclide imaging is widely used, especially for evaluating myocardial viability.
Quantification of Left Ventricular Function and Volumes
The acquisition of ECG-gated myocardial perfusion images allows quantification of regional and global systolic function, and left ventricular volumes. ECG-gated images typically are collected at rest and after stress (SPECT) or during stress (PET). Rest left ventricular ejection fraction (LVEF) measurements are helpful to define the patient’s risk for a cardiovascular event after MI. A drop in LVEF after or during stress testing can be helpful to identify high-risk patients with multivessel CAD.
Accuracy of Radionuclide Imaging for Identification of Flow-Limiting Coronary Artery Disease
The most relevant clinical issue in post-MI patients is not the diagnosis of CAD, which is already established, but rather the identification of residual flow-limiting stenosis in the infarct-related artery and/or non–culprit coronary arteries. Traditionally, diagnostic accuracy of physiologic imaging methods for CAD assessment has been defined using a threshold of 50% or 70% stenosis on coronary angiography. This traditional measure, however, has limited clinical applicability, because it is now clear that more than two thirds of angiographic stenoses are not flow-limiting when assessed by a physiologic gold standard such as fractional flow reserve (FFR). A recent meta-analysis has evaluated the relative accuracy of myocardial perfusion imaging techniques including radionuclide imaging (SPECT and PET), echocardiography, MRI, and CT for identifying flow-limiting stenosis as assessed by FFR. Thirty-seven studies reporting on 4721 vessels and 2048 patients were included. On a patient-based level, PET, MRI, and CT had higher sensitivity and negative predictive value compared with SPECT and echocardiography. Similar results were observed on a vessel-based analysis ( Table 32-2 ).