Cardiac PET and PET/CT

30Cardiac PET and PET/CTAmol Takalkar, Eugene C. Lin, Elias Botvinick, Adam M. Alessio, and Luis Araujo

Myocardial Perfusion Assessment

Clinical Indication: A

Myocardial perfusion assessment at rest and with stress (exercise or pharmacologic) is important in patients with known or suspected coronary artery disease (CAD). Single-photon emission tomography (SPECT) myocardial perfusion imaging with thallium or technetium 99m labeled agents is routinely practiced. However, SPECT imaging has several limitations and myocardial perfusion imaging with positron emission tomography (PET) is superior to SPECT. In practice, PET myocardial perfusion imaging is constrained by the need for an on-site cyclotron to perform nitrogen 13 ammonia imaging. Rubidium 82 imaging can be performed with a generator. Given the cost of the generator and current reimbursements, 2 to 3 studies a day may need to be performed for PET to be cost-effective.

Tracers

Nitrogen 13 (¹³N) ammonia (cyclotron-produced) and rubidium 82 (⁸²Rb) chloride (generator produced) are Food and Drug Administration (FDA)-approved PET radiopharmaceuticals for assessing myocardial blood flow. Oxygen 15 (¹⁵O) labeled water and ⁶²Cu-pyruvaldehyde bis (N4-methylthiosemicarbazone) (Cu-PTSM) can also be used but are mostly restricted to the research setting.

⁸²Rb can be eluted from a strontium 82 generator, which needs to be replaced approximately every 4 weeks. The half-life of ⁸²Rb is 75 seconds.

¹³N ammonia has a half-life of ~10 minutes.

The advantages of ⁸²Rb are that a cyclotron is not needed, and it is ideal for peak dipyridamole or regadenosan stress gated imaging. Rb-82 as imaging typically starts 90 to 120 seconds after injection compared with 3 to 5 minutes with ¹³N ammonia. The disadvantages are poorer resolution (due to a positron range of 2.6 mm), lower extraction, and more difficulty with quantitation compared with ¹³N ammonia. It is also very difficult to perform exercise stress testing with ⁸²Rb, given the short half-life of the tracer.

Protocols

Fig. 30.1 Rest and dipyridamole stress myocardial perfusion positron emission tomography rubidium 82 images displayed conventionally in the short, vertical, and horizontal long axes, showing normal myocardial perfusion at rest and stress. (Courtesy of Elias Botvinick, MD, San Francisco, CA.)

Accuracy and Comparison with Other Modalities

PET imaging provides better spatial and temporal resolution and hence is better suited in patients with thick/muscular chest wall, large breast tissue, or overall body habitus that frequently leads to indeterminate SPECT myocardial perfusion studies (Fig. 30.3). Due to the short half-life of the PET tracers, pure stress-related images uncontaminated by the prior rest injection can be obtained. Unlike gated SPECT, left ventricular ejection fraction can be assessed at peak stress, as imaging is performed soon after injection. PET imaging, with absolute quantification of regional radiotracer uptake, is better suited when serial studies are required to assess perfusion in a particular myocardial segment. It also allows better evaluation of endothelial dysfunction and coronary flow reserve as a measure of coronary stenosis. Moreover, PET allows for more efficient imaging protocols, leading to faster studies (around 45 minutes compared with 3 to 4 hours for SPECT studies) and lower radiation exposure.

Numerous studies have shown that myocardial perfusion PET has higher accuracy,² sensi-tivity,³ and specificity⁴ compared with SPECT.

Pitfalls

If ¹³N ammonia is used for perfusion imaging, there is decreased lateral wall activity in ~10% of normal patients. The etiology of this is unknown.
Misregistration artifact during a cardiac PET/ computed tomography (CT) scan can result in artifactual defects (see Pitfalls in Myocardial Viability section).

Myocardial Viability

Clinical Indication: A

PET imaging with fluorodeoxyglucose (FDG) with myocardial perfusion imaging is the current gold standard for the assessment of myocardial viability.

Fig. 30.2 (A) Rest and dipyridamole stress myocardial perfusion positron emission tomography (PET) rubidium 82 images showing a large region of ischemia in the anterior wall, anterior septum, and anterior and midlateral walls and gross stress-induced cavitary dilation by conventional display. (B) The polar map shows the defect distribution and magnitude. (C) A model three-dimensional ventricle fused with a model coronary tree (can be patient’s own coronary tree if the patient had undergone a PET study with computed tomography coronary angiography) showing the extent and density of the abnormality. (Courtesy of Elias Botvinick, MD, San Francisco, CA.)
Demonstration of significant viable myocardium in a patient with chronic ischemic heart disease with left ventricular (LV) dysfunction indicates a need for prompt revascularization and predicts low perioperative mortality and morbidity, significant improvement in left ventricular ejection fraction (LVEF) and congestive heart failure (CHF) symptoms, and improved survival.
Absence of viable myocardium in a patient with chronic ischemic heart disease with LV dysfunction supports the decision for medical management and/or cardiac transplantation.

Clinical Scenario

Patients with severe LV dysfunction and CAD continue to pose a significant management dilemma to clinicians who frequently need to choose between aggressive medical treatment and revascularization therapy.⁵ Revascu-larization therapy results in better long-term survival rates, and several investigators have demonstrated the benefit of revascularization in CAD patients with poor LV function.^6–14 However, it is associated with significant periprocedure morbidity and mortality, making identification and selection of only those patients who will benefit maximally from revascularization extremely crucial. Improvement in the LV function after revascularization is mainly dependent on the reversibility of contractile dysfunction. Dysfunctional but “viable” myocardium is said to be reversibly dysfunctional, whereas scar tissue usually results in nonreversibly dysfunctional myocardium. Thus, accurate identification of myocardial viability is a critical component in the diagnostic work-up of these patients.

Fig. 30.3 (Continued) (A) Rest thallium 201 and dipyridamole pharmacologic stress technetium 99m sestamibi single-photon emission tomography myocardial perfusion images of an obese 63-year-old woman with atypical chest pain showing irregular uptake with an apparent fixed inferior wall defect with possible stress induced abnormality in the lateral wall, (B) also well seen on the model left ventricular display. (C) A repeat pharmacologic stress imaging study performed with positron emission tomography shows normal rest and stress perfusion (D) with normal ventricular model of myocardial uptake. (Courtesy of Elias Botvinick, MD, San Francisco, CA.)

Mechanism of Myocardial Ischemia

Myocardial ischemia may result from acute coronary artery occlusion or from chronic hypoperfusion or repetitive ischemic processes. The severity and duration of myocardial ischemia will determine the myocardial response to the ischemic process. Although the myocardium has several immediate as well as sustained mechanisms of adaptations (e.g., hibernation, stunning and ischemic preconditioning 15–17) to withstand acute and chronic ischemia, the end result of ischemic injury is a mechanically dysfunctional myocardium. The dysfunctional myocardium may be related to ischemic but viable myocardium, such as stunned or hibernating myocardium or necrosed and scarred myocardium that may be completely nonviable (Fig. 30.4).

Fig. 30.4 Myocardial response to ischemia.

Fig. 30.5 Protocol to assess myocardial viability with positron emission tomography. FDG, fluorodeoxyglucose.

Fig. 30.6 (A) A rest rubidium 82 perfusion image with a rest fluorine 18 fluorodeoxyglucose (FDG) scan in a patient with known coronary artery disease and recent myocardial infarction for viability evaluation showing perfusion in all regions except the left ventricular apex, related anterior wall, and inferiorlateral wall, which show positive FDG uptake (mismatch), indicating regional viability and a high likelihood of functional improvement after bypass graft surgery. (B) The findings are superimposed on a model left ventricle, where defects are shown in blue. (Courtesy of Elias Botvinick, MD, San Francisco, CA.)

Identification of Myocardial Viability by PET

The normal myocardium preferentially uses free fatty acids (FFAs) as energy substrates during normal fasting conditions. During hypoxia and ischemia, FFA oxidation is markedly decreased, and the rate of anaerobic glycolysis is enhanced. Thus, the ischemic myocardium uses glucose in preference to FFAs as the energy substrate.18–27 FDG PET can reliably and accurately assess the initial steps of glucose metabolism in the ischemic myocardium by evaluating myocardial glucose uptake. The protocol for assessing myocardial viability using PET and ¹³N ammonia for myocardial perfusion imaging and FDG for myocardial metabolism imaging is depicted in Fig. 30.5.

**Table 30.1** Sensitivity and Specificity of Various Methods to Assess Myocardial Viability
Imaging Method	Sensitivity %	Specificity %
PET	93	58
Thallium	86	59
rest-redistribution
Thallium reinjection	88	50
Technetium tracers	81	66
Dobutamine echo	81	80