CHAPTER 53 Magnetic Resonance and Computed Tomographic Imaging of Myocardial Perfusion

Ricardo C. Cury, Anand Soni, Ron Blankstein

Ischemic heart disease is a broad term that includes many different disease processes related to coronary atherosclerosis and its downstream consequences. On a continuum, it encompasses silent myocardial ischemia, chronic stable angina, acute coronary syndromes (ACS), and ischemic cardiomyopathy. All of these disease processes typically share the same underlying mechanism of reduced myocardial perfusion from obstructive coronary plaque, which results in myocardial ischemia or myocardial infarction (MI) from oxygen deprivation.

Data from the National Health and Nutrition Examination Survey (1999-2004, National Heart, Lung and Blood Institute) estimate the prevalence of coronary heart disease to be 16 million individuals in the United States, and incidence of new and recurrent coronary events to be 1.2 million per year.¹ Data from 44 years of follow-up in the original Framingham Heart Study cohort and 20 years of their offspring surveillance show the lifetime risk of developing coronary heart disease for individuals 40 years old to be 49% in men and 32% in women.² With mortality statistics claiming that one out of every five deaths is the result of coronary artery disease (CAD),¹ there is a clear need for improved diagnostic imaging strategies for detecting coronary heart disease and myocardium vulnerable to scenarios of reduced perfusion.

Myocardial ischemia is caused by inadequate coronary perfusion as a result of either an increase in myocardial oxygen requirements or a reduced supply of oxygen-carrying blood. Typically, myocardial ischemia is the result of atherosclerotic CAD. Initially, atherosclerotic vascular disease starts as atheromatous fatty streak buildup within the arterial wall, but in which there is no reduction in coronary blood flow (also known as “positive” remodeling) and patients remain asymptomatic. With further disease progression, there is mild to moderate buildup in plaque, which poses no limits to coronary perfusion at rest or stress, but poses the risk of being “unstable” and abruptly rupturing. If these plaques rupture, the thrombotic consequences can result in near-complete or complete coronary occlusion with severe acute reduction of myocardial perfusion; this is the framework for ACS. Lastly, atherosclerotic plaque may be large enough nearly to obstruct the coronary lumen (also known as “negative” remodeling). This lesion tends to cause reduced myocardial perfusion at times of stress and provides the basis for stable angina.

The clinical presentation of ischemic heart disease is incredibly diverse and includes asymptomatic or silent ischemia, chronic angina, unstable angina or infarction (i.e., ACS), new-onset or chronic heart failure, or sudden cardiac death. Although symptomatic patients are often identified by symptoms related to angina or heart failure, patients who have silent ischemia represent a diagnostic dilemma because they are less likely to be referred for testing. Patients who are particularly susceptible to silent ischemia include diabetics, elderly patients, and patients with prior MI or surgical revascularization.³

Noninvasive imaging is a crucial component in the evaluation of patients with suspected ischemic heart disease. Figure 53-1 illustrates an algorithm for the management of patients with potential ischemic heart disease. For patients presenting with a possible ACS who have a negative ECG and biomarkers (e.g., troponin), a stress test can be used to identify high-risk patients who would benefit from being admitted to the hospital for further evaluation and testing. The American College of Cardiology/American Heart Association guidelines for the management of unstable angina/non–ST segment elevation MI suggest that coronary CT angiography is a reasonable alternative to stress testing in patients with low to intermediate probability of CAD in whom initial ECG and initial biomarkers are unremarkable.⁴

FIGURE 53-1 Algorithm for management of patients with suspected ischemic heart disease. CCS, Canadian Classification System; CHF, congestive heart failure; CTA, CT angiography; DC, discharge; EF, ejection fraction; HF, heart failure; LBBB, left bundle branch block; OMT, optimal medical therapy; Pharm stress, pharmacologic stress testing; PTP, pretest probability; SE, stress echocardiogram; UA, unstable angina.

(Data from Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [Writing Committee to Revise the 2002 Guidelines for the Management of Patients with Unstable Angina/Non ST-Elevation Myocardial Infarction]: developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation 2007; 116:e148-e304; and Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [Committee on the Management of Patients with Chronic Stable Angina]. Circulation 2003; 107:149-158.)

Patients who are admitted with an ACS can be treated with an early invasive or early conservative strategy. High-risk patients have been shown to benefit from early interventions, and warrant early referral for invasive angiography. For low-risk patients, and in particular women, a conservative strategy that uses noninvasive testing is recommended.⁴

For patients with chronic stable angina, the American College of Cardiology/American Heart Association guidelines ⁵ suggest that ejection fraction should be measured for all patients with a history of MI or signs suggesting heart failure. In the presence of a systolic murmur suggestive of aortic stenosis, mitral regurgitation, or hypertrophic cardiomyopathy, an echocardiogram should be obtained.

As is shown in Figure 53-1, all patients with chronic angina (i.e., stable angina) should have an evaluation for the presence of ischemic heart disease. This evaluation can be accomplished by ECG exercise testing, noninvasive stress imaging, or invasive angiography. Higher risk patients or patients with abnormal baseline ECG should be referred for an imaging-based test. The goal of such a test is to identify the extent, severity, and location of ischemia and when possible provide information about prognosis.

The role of cardiac imaging for the detection of silent ischemia is controversial. Patients with diabetes may benefit from such a strategy because they have a high risk of cardiovascular-related mortality, are more likely to have silent ischemia, and are less likely to survive an MI than nondiabetic patients.⁶ Nevertheless, the cost-effectiveness of screening all such at-risk patients with nuclear perfusion imaging is controversial.⁷

The detection of myocardial perfusion abnormalities is mainly used to identify patients with CAD, to evaluate the hemodynamic significance of epicardial coronary stenosis, and to enhance clinical decisions regarding treatment options. Myocardial perfusion imaging (MPI) assessment is frequently performed using rest and stress studies to detect myocardial ischemia (reversible defects) and myocardial infarct (fixed defects).

At present, multiple noninvasive imaging modalities are used in evaluating myocardial perfusion, including single photon emission computed tomography (SPECT), positron emission tomography (PET), echocardiography, and MRI. Although SPECT has been well shown to assess rest and stress perfusion accurately, and provides useful prognostic data based on a patient’s burden of ischemia and infarct, it is limited by its low spatial resolution and attenuation artifacts, which can lead to equivocal studies. ¹⁸FDG-PET has the ability to evaluate myocardial ischemia using radiotracers such as ammonia N 13 or rubidium 82, but has limitations regarding availability. MRI shows promise in the evaluation of myocardial ischemia with first-pass perfusion imaging, and large-scale multicenter trials are just beginning to be released. CT has the best spatial resolution of any imaging modality, and many emerging studies are suggesting it may have an important role for the future evaluation of myocardial perfusion and infarct detection.

This chapter focuses on the evaluation of MRI and CT for the assessment of myocardial perfusion (Figs. 53-2 and 53-3). The advantages and disadvantages of other imaging modalities are discussed and compared with MRI and CT, and these imaging modalities are put in clinical perspective with descriptions of how and when they can facilitate the diagnosis and management of patients suspected to have CAD or with known CAD.

FIGURE 53-2 A 55-year-old man presented with ST segment elevation MI. A, Invasive coronary angiography revealed a significant high-grade stenosis of the distal right coronary artery (arrow). The patient underwent cardiac CT and MRI 3 days later. B, Short-axis CT image showed a perfusion defect (arrow) in mid-inferior and inferolateral wall of the left ventricle. C, MRI first-pass perfusion showed a resting perfusion defect in the same corresponding territory (arrow). D, MDE MRI showed a large area of hyperenhancement (arrows) in the mid-inferior, inferolateral, and inferoseptal walls of the left ventricle with a greater than 50% transmurality. The hyperenhancement pattern was based in the subendocardium and was consistent with a large MI. Within the infarct, a smaller region of no hyperenhancement (arrowhead) was noted that corresponds to a region of no reflow (also known as microvascular obstruction).

FIGURE 53-3 A 40-year-old man was transferred from an outside hospital with MI. A, During invasive coronary catheter angiography, he was found to have a complete occlusion of the left circumflex coronary artery (arrow). B and C, Short-axis (B) and long-axis (C) CT images showed a large perfusion defect of the entire lateral wall (arrows). D, First-pass perfusion MRI confirms this and shows a large perfusion defect of the inferolateral wall (arrow). MDE MRI shows the extent of the MI. Within the area of hyperenhancement, there is a substantial central area that lacks hyperenhancement, representing microvascular obstruction (arrowhead).

MAGNETIC RESONANCE IMAGING

The goal of stress myocardial perfusion MRI is to visualize the first pass of gadolinium contrast agent within the left ventricle blood pool into the myocardium during rest and stress. Stress is achieved with pharmacologic vasodilation with either adenosine or dipyridamole. Under vasodilatory stress, myocardial blood flow should increase four to five times except in areas of obstructive epicardial CAD, where downstream vascular beds are already maximally vasodilated. These coronary territories obtain lower peak myocardial signal intensity on contrast administration compared with resting conditions, and a myocardial perfusion defect is visualized.

Preclinical and Clinical Evaluation

Numerous animal studies have shown good correlation of MRI perfusion with tissue perfusion as measured by radioactive microspheres.⁸^,⁹ Notable studies included work by Wilke and colleagues and Klocke and associates,⁸ in which porcine and canine models of left circumflex coronary artery stenosis were created that showed that MRI can detect different degrees of myocardial perfusion under adenosine stress.

Subsequently, Lee and colleagues ⁹ used a canine model of left circumflex coronary artery stenosis and compared perfusion MRI with Tc 99m sestamibi and thallium 201. They showed that MRI could detect perfusion defects with a left circumflex coronary artery stenosis of 50% or greater, whereas SPECT perfusion defects were detected only with left circumflex coronary artery stenosis of 85% or greater.

Multiple clinical human studies testing the diagnostic accuracy and performance of stress perfusion MRI were performed comparing MRI with nuclear imaging and conventional coronary angiography. Table 53-1 summarizes published data with x-ray angiography as the reference standard. Nandalur and associates¹⁰ performed a meta-analysis of all stress MRI studies with two main techniques in use, perfusion imaging and imaging of stress-induced wall motion abnormalities, from January 1990 to January 2007 with a total of 37 studies involving 2191 patients. All studies used catheter x-ray angiography as the reference standard. Fourteen studies (N = 754 patients) using stress-induced wall motion abnormalities imaging showed 83% sensitivity and 86% specificity on a patient level. Perfusion imaging showed a sensitivity of 91% and specificity of 81% on a patient level (disease prevalence 57.4%).

TABLE 53-1 Diagnostic Accuracy of Stress Perfusion Magnetic Resonance Imaging Studies, Having Invasive Coronary Angiography as the Reference Standard

Two more recent studies by Cury and associates ¹¹ and Klem and coworkers¹² (see Table 53-1) sought to improve the diagnostic accuracy of stress perfusion MRI by using a comprehensive imaging approach of first-pass contrast administration for myocardial perfusion at rest and stress with the addition of myocardial delayed enhancement (MDE) imaging for infarct detection and characterization. Our group showed that this combined approach has 87% sensitivity, 89% specificity, and 88% accuracy, and was superior to rest/stress perfusion MRI alone, which has 81% sensitivity, 87% specificity, and 85% accuracy, having invasive coronary angiography as the reference standard. Klem and coworkers¹² showed similar results—that stress perfusion and MDE MRI can better detect inducible ischemia and fixed defects compared with stress/rest perfusion MRI. MDE MRI also provides the benefit of improved identification of regions of no reflow or microvascular obstruction, which is readily identified on MDE as regions of no hyperenhancement within the hyperenhancing infarction (see Figs. 53-2 and 53-3).

In another study evaluating patients presenting to the emergency department with acute chest pain, Ingkanisorn and colleagues ¹³ evaluated the diagnostic value of adenosine stress myocardial perfusion MRI in 135 patients who presented to the emergency department with chest pain and a negative initial troponin value. The main study outcome was the detection of any evidence of significant CAD. Patients were contacted at 1 year to determine the incidence of significant CAD, defined as significant coronary artery stenosis (>50%) on invasive coronary angiography, abnormal correlative stress test, new MI, or death. Adenosine myocardial perfusion MRI abnormalities had 100% sensitivity and 93% specificity for detection of significant CAD, and an abnormal MRI added significant prognostic value in predicting a future diagnosis of CAD, MI, or death over clinical risk factors. No patients with a normal adenosine myocardial perfusion MRI had a subsequent diagnosis of CAD or an adverse outcome.

The first multicenter trial involving 18 centers in Europe and the United States (MR-IMPACT trial) comparing stress myocardial perfusion MRI with SPECT imaging and invasive coronary angiography was published more recently.¹⁴ When comparing perfusion MRI at 0.1 mmol/kg versus the entire SPECT population, the receiver operating curve analysis showed a better performance for perfusion MRI (n

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