1. What is nuclear cardiology?
Nuclear cardiology is a field of cardiology that encompasses cardiac radionuclide imaging, which uses radioisotopes to assess myocardial perfusion or myocardial function in different clinical settings, as well as radionuclide angiography, metabolic and receptor imaging, and positron emission tomography.
2. What is myocardial perfusion imaging?
Myocardial perfusion imaging (MPI) is a noninvasive method that utilizes radioisotopes to assess regional myocardial blood flow, function, and viability. The basis for MPI rests on the ability of this technique to demonstrate inhomogenity of blood flow during stress compared with rest, thereby identifying ischemic regions.
During the stress portion of the test, exercise or a pharmacologic agent is used to produce vasodilation in the coronary vascular bed. Whereas a normal vessel can vasodilate and increase coronary blood flow up to four times basal blood flow, a diseased or stenotic vessel cannot. Because radiotracer uptake into the myocardium is dependent on blood flow, the areas that are supplied by normal vessels in which there is maximally increased blood flow will take up more radiotracer than areas supplied by the stenotic vessel with relatively less blood flow. Therefore, there will be heterogeneous radiotracer uptake, which will be seen as a perfusion defect.
3. Define a perfusion defect and differentiate between a reversible and fixed defect. A perfusion defect is an area of reduced radiotracer uptake in the myocardium.
If the perfusion defect occurs during stress and improves or normalizes during rest, it is termed reversible (Fig. 8-1). Generally, a reversible perfusion defect suggests the presence of ischemia.
If the perfusion defect occurs during both stress and rest, it is termed fixed. Generally, a fixed defect suggests the presence of scar. However, in certain settings a fixed defect may not be scar. Instead, a fixed defect may represent viable tissue that is hibernating due to chronic stenosis. Hibernating myocardium alters its metabolism in order to conserve energy. Therefore, it appears underperfused and has hypokinetic or akinetic function.
4. What are the different uses of myocardial perfusion imaging?
MPI is used to diagnose coronary artery disease (CAD) in patients with intermediate risk for CAD who present with chest pain or its equivalent.
MPI can be used to localize and quantify perfusion abnormalities or physiologic ischemia in patients with known CAD.
MPI can be used to assess the presence of viability in areas of fixed defects using rest and redistribution studies with thallium.
MPI can also be used for risk assessment and determination of prognosis with regard to cardiovascular events. It can be used as a prognostic tool in post MI patients, including patients with and without ST elevation, to identify further areas of myocardium at risk.
MPI can also be used in preoperative assessment to identify perioperative or postoperative cardiovascular risk. The extent and severity of perfusion defects are proportional to the risk of perioperative cardiac events.
-1.jpg)
Figure 8-1. Nuclear stress testing short-axis view demonstrating a reversible perfusion defect. Normal myocardial perfusion occurred during resting images (left panel), but a large anterior wall perfusion defect (arrows) was seen during previous stress imaging (right panel).
5. Is MPI the most sensitive and specific test for diagnosing CAD?
The ischemic cascade suggests that MPI would be a more sensitive test to detect ischemia because in the setting of ischemia, a perfusion abnormality occurs before a wall motion abnormality. The sensitivity of an MPI is slightly better than stress echocardiography (85% versus 75%, respectively) and the specificity slightly worse (79% versus 88%). This results in similar accuracy for both types of stress tests. Both modalities are more sensitive and specific than treadmill or exercise electrocardiography testing, although according to the American Heart Association/American College of Cardiology (AHA/ACC) guidelines, the latter should be the first-line test for the diagnosis of CAD in someone who can exercise and has a relatively normal electrocardiogram (ECG).
6. List the different perfusion agents used in myocardial perfusion imaging.
For an agent to be an effective radiopharmaceutical, its distribution has to be proportional to regional blood flow and it has to have a high level of extraction by the organ of interest and rapid clearance from the blood. The two most important physiologic factors that affect myocardial uptake of a radiotracer are variations in regional blood flow and the myocardial extraction of the radiotracer. In other words, there will be more uptake of a radiotracer in areas of increased blood flow and less in areas supplied by diseased or stenosed vessels. Importantly, because myocardial extraction is an active process with regard to thallium-201 and a mitochondrial-dependent process with regard to the technetium-99m agents, it can only occur if the cells in that region are viable. The relative advantages and disadvantages of thallium-201 and technitium-99 are summarized in Table 8-1.
-2.jpg)
Thallium-201 (Tl-201) is a potassium analog used for MPI. It is the oldest and best studied of the present-day agents. Thallium distribution is dependent on blood flow and tracer extraction by the myocardium. It enters the myocardium by active transport of membrane-bound NaþKþATPase. One of the most important characteristics of Tl-201 is its myocardial redistribution. A dynamic quality to the uptake of Tl-201 gives it the ability to redistribute over time. There is continued influx of Tl-201 over time from the blood-pool activity and a clearance or washout from the myocardium. This phenomenon results in normalization or reversibility in areas that are ischemic, and over additional time improvement or normalization can occur in areas that are viable but appeared as scar during the first rest imaging.
Technetium-99m (Tc-99m) comprises many radiotracers. Some agents include Tc-99m sestamibi, Tc-99m teboroxime (not used clinically at present), Tc-99m tetrofosmin, and Tc-99m N-NOET.
Tc-99m sestamibi (or MIBI or Cardiolite) is the third of the isonitriles to be developed but the first of the Tc-99m agents to be approved for commercial use. It contains a hydrophilic cation and the isonitrile hydrophobic portion that allows for the necessary interactions with the cell membrane for uptake into the myocardioum. The uptake of MIBI is dependent on mitochondrial-derived membrane electrochemical gradient, cellular pH, and intact energy production. Unlike Tl-201, MIBI does not possess a strong redistribution quality. The reason for this is that the clearance of MIBI is slow even though continued uptake occurs during the rest phase of a study. Therefore, there may be some improvement in 2 to 3 hours between stress and rest, but the degree of redistribution is slower and less complete than Tl-201. Importantly, however, only viable tissue can extract and uptake MIBI.
Tc-99m tetrofosmin (Myoview) is the newest of the Tc-99m agents to be approved for clinical use. Its properties are similar to MIBI, although the mechanism by which myocardial uptake occurs is not well elucidated; however, uptake is dependent on intact mitochondrial potentials (i.e., viable cells). Studies show similar characteristics to MIBI, with a more rapid clearance from the liver allowing for faster imaging times.
Tc-99m furifosmin is similar to Tc-99m tetrofosmin but is not currently approved for clinical use.
Tc-99m N-NOET is a newer investigational agent that has similar physical and imaging properties to that of other Tc-99m agents but also favorable redistribution qualities similar to Tl-201.
7. How is stress produced for MPI in the evaluation of CAD?
Stress can be produced in different ways. The goal of myocardial perfusion imaging is to produce vasodilation in order to assess the presence of diseased or stenotic vessels, which will vasodilate to a lesser extent than healthy, nonstenotic vessels. Forms of stress are either exercise or pharmacologic (Table 8-2).
-3.jpg)
Exercise can include treadmill, supine or erect bicycle, dynamic arm, or isometric handgrip. Generally, because of its diagnostic and prognostic value, the treadmill is used most often. Functional capacity can be determined. In addition, prognosis for cardiac events can be determined using the Duke treadmill score when using the Bruce protocol. Exercise increases myocardial blood flow and metabolic demand.
Pharmacologic agents include dobutamine, dipyridamole, and adenosine. ○ Dobutamine is a b-1 agonist that increases heart rate and contractility and thereby produces an indirect increase in myocardial blood flow as a result of increased metabolic demand. This agent is used for nuclear stress MPI when vasodilators are contraindicated, such as in bronchospastic lung disease or bradycardia and heart block. ○ Dipyridamole and adenosine are both vasodilators. They purely produce vasodilation by acting on the adenosine receptors. Dipyridamole does this by increasing the endogenous levels of adenosine by preventing its breakdown, whereas adenosine is given exogenously to increase levels. They do not affect myocardial metabolic demand.
8. How much radiation exposure does a patient get from a typical myocardial perfusion imaging study? How does it compare to other cardiac studies?
It depends on the radiotracer used and the protocol. Exposure can vary from about 10 mSv to upwards of 30 mSv. Table 8-3 summarizes radiation exposure from various tests.
-4.jpg)
9. Is it possible to assess both myocardial perfusion and left ventricular function with one study?
Yes. Both Tc-99m agents and Tl-201 have been validated in assessing left ventricular (LV) volumes and left ventricular ejection fraction (LVEF) using gated single-photon emission computed tomography (SPECT) imaging. Thus, one can gate stress and rest portions of the MPI when using gated SPECT technology. Gating is a method of stopping cardiac motion that allows for the assessment of the different phases of the cardiac cycle. This triggering of the imaging camera at the onset of the R wave over multiple cardiac cycles provides an 8- or 16-frame average of multiple cardiac beats, which are needed to accurately assess wall motion and thickening. Gated studies improve specificity by helping to differentiate fixed defects caused by attenuation versus scar.
10. Functional assessment of cardiac performance is determined using which nuclear cardiology techniques?
The term radionuclide angiography encompasses both the first-pass bolus technique and gated equilibrium blood pool imaging, both of which can be used to assess LV function.
First-pass radionuclide angiography (FPRNA) uses a bolus technique and rapid acquisition to track the tracer bolus through the right atrium, right ventricle, pulmonary arteries, lungs, left atrium, left ventricle, and finally aorta. The first-pass technique can be used to assess both left and right ventricular ejection fraction, regional wall motion, and cardiopulmonary shunts. FPRNA can be done both at rest and during exercise.
Gated equilibrium blood pool imaging or multiple gated acquisition (MUGA) can also be used to assess left ventricular function and ejection fraction. The right ventricle is not easily assessed with this technique because of overlap of cardiac structures but can be done if care is taken in imaging. The technique is performed after a sample of the patient’s red blood cells is labeled with Tc-99m sodium pertechnetate and then reinjected for planar imaging in three different views. The gating is done similar to SPECT gating; however, instead of a standard number of frames per cardiac cycle, there can be a variable number depending on the R to R cycle length or heart rate. The cardiac images are then compiled into summed images. They are then processed and displayed as a continuous cinematic loop. From the cinematic loop, one can assess wall motion in the different views, including left anterior oblique (LAO), lateral, and anterior. The data from the LAO view is also displayed as still images so that the counts in the region of interest (the left ventricle) at end-systole and end-diastole can be used to calculate the end-diastolic volume (EDV) and end-systolic volume (ESV) and subsequently the ejection fraction.
Importantly, this technique can be done both at rest and during stress to give accurate volumetric information for comparison.
11. Why should one use radionuclide angiography to assess LVEF?
It is a precise and accurate measure of LVEF that is more reproducible than echocardiography, especially when doing serial studies to look for changes in LVEF caused by cardiotoxic agents, valvular heart disease, and new therapeutic agents in clinical trials.
It is less expensive and more feasible than magnetic resonance imaging for evaluation of LVEF.
On a more practical level, radionuclide angiography can be used to assess LVEF when other methods are not possible because of poor images as a result of body habitus, lung disease, or chest wall deformities.
LVEF is an independent predictor of cardiac events and thus serves as a valid prognostic index in many clinical settings.
12. What is the role of positron emission tomography (PET) in the assessment of the heart, in particular CAD?
PET has many capabilities, including assessing myocardial blood flow, glucose utilization, fatty acid metabolism, oxidative metabolism, oxygen consumption, and adrenergic neuronal activity and b-receptor densities.
Tracers used to assess myocardial blood flow include O-15 water, Rb-82, and N-13 ammonia. Tracers used to assess metabolism include F-18-fluoro-2-deoxyglucose (F-18 FDG), carbon-11-labeled palmitate and acetate, and molecular oxygen-15.
The most useful tool that PET provides in the assessment of CAD is identifying viable tissue. The issue of viability is raised when a myocardial segment appears as scar such that it has reduced perfusion and contractility in both stress and rest imaging. Combined PET imaging with N-13 ammonia or rubidium perfusion and F-18 FDG for glucose metabolism is considered the gold standard to assess myocardial viability. Viable myocardium is identified on the basis of myocardial blood flow and preserved or enhanced substrate utilization. First a segment with impaired contractility is identified. Then the relative blood flow to that region is assessed, followed by determination of the regional metabolic activity. The importance of assessing viability is illustrated by outcomes after revascularization of viable and nonviable regions. Table 8-4 summarizes the interpretation of PET testing for myocardial viability.
-6.jpg)
