Principles of myocardial perfusion imaging (SPECT, PET), coronary blood flow and flow reserve (CFR)

Principles of myocardial perfusion imaging

Myocardial perfusion imaging (MPI) is a non-invasive technique for detecting and quantifying coronary artery disease (CAD). It offers visual and numerical insights into myocardial blood flow under rest and stress conditions. MPI uses radiotracers in combination with single photon emission computed tomography (SPECT) or positron emission tomography (PET) to assess myocardial perfusion and blood flow. These imaging modalities are highly sensitive and specific in evaluating perfusion and also play a role in determining the viability of compromised myocardial tissue, aiding revascularization decisions when the potential benefits are uncertain.

Myocardial perfusion imaging is based on the principle that myocardial blood flow demonstrates marked differences between rest and stress conditions, particularly in significant coronary artery stenosis. Stress can be induced pharmacologically with coronary vasodilatory agents or simulated hemodynamically through exercise or the use of chronotropic and inotropic agents. Radiotracers are employed to evaluate myocardial perfusion by measuring the intensity of their uptake within the myocardium. Furthermore, certain radiotracers enable direct measurement of coronary blood flow, providing absolute quantification.

The resting myocardium rarely reveals evidence of significant coronary artery stenosis unless the stenosis is severely critical, potentially causing angina during rest. Patients experiencing angina at rest are not suitable candidates for perfusion imaging. Detecting ischemic regions requires provocation using pharmacologic agents or physical exercise. Pharmacologic agents include dipyridamole, adenosine, regadenoson, and dobutamine. Dobutamine increases myocardial oxygen demand, while dipyridamole, adenosine, and regadenoson create blood flow disparities between healthy and diseased coronary arteries, allowing ischemia to be detected during imaging.

Exercise is the preferred method for inducing myocardial stress, as it provides additional diagnostic and prognostic information, including symptoms, heart rate response, blood pressure changes, ECG changes, arrhythmias, and exercise (functional) capacity. Functional capacity is a strong predictor of both cardiovascular and overall mortality, offering incremental prognostic data beyond perfusion imaging and ECG reaction.

Coronary blood flow and coronary flow reserve (CFR)

Coronary blood flow is the volume of blood flowing through the coronary arteries per unit of time. Coronary flow reserve (CFR) quantifies the capacity of coronary arteries to augment blood flow in response to increased myocardial oxygen demand, such as during physical exertion. It is defined as the ratio of maximal coronary blood flow during stress to the resting flow (Goodwill et al).

Coronary autoregulation refers to the ability of the coronary arteries to maintain a relatively constant myocardial blood flow despite changes in coronary perfusion pressure, typically within a range of 50-120 mmHg. This process is primarily mediated by local metabolic mechanisms, which adjust vascular tone in response to myocardial oxygen demand, and myogenic responses, where vascular smooth muscle constricts or dilates in response to changes in intraluminal pressure. Coronary blood flow is also influenced by sympathetic and parasympathetic influences; sympathetic stimulation leads to vasoconstriction through the release of norepinephrine, while parasympathetic activation can cause vasodilation via acetylcholine release. These mechanisms collectively modulate coronary vascular resistance to ensure that myocardial oxygen supply matches demand (Duncker et al).

Reference values for coronary blood flow

• Normal coronary blood flow at rest: 0.6 to 1.3 mL/min/g of myocardial tissue
• During hyperemia (maximum stress): Approximately 3.58 ± 1.14 mL/min/g
• Total hyperemic flow for the whole heart: Approximately 670 mL/min

Reference values for coronary flow reserve (CFR)

• Normal CFR: >2.0 to >2.5
• Young, healthy individuals may have a CFR of 5.0 or 6.0
• CFR tends to decrease with age, with healthy elderly individuals potentially having a CFR below 2.0

The lower reference limit for coronary flow reserve (CFR) is typically defined as 2.0 to 2.5, with values below this range associated with elevated cardiovascular risks. A systematic review by Kelshiker et al reported the following, with regards to low CFR:

• Increased mortality risk: A CFR below 2.0 is strongly associated with higher all-cause mortality (HR: 3.78, 95% CI: 2.39–5.97.
• Elevated risk of major adverse cardiovascular events (MACE): CFR values under 2.0–2.5 are correlated with an increased risk of MACE (HR: 3.42, 95% CI: 2.92–3.99.
• Coronary microvascular dysfunction: In patients with isolated microvascular dysfunction, abnormal CFR is linked to higher mortality (HR: 5.44, 95% CI: 3.78–7.83) and MACE (HR: 3.56, 95% CI: 2.14–5.90).
• Impaired vasodilator reserve: Reduced CFR may indicate a diminished ability of coronary arteries to dilate adequately in response to increased myocardial oxygen demand.
• Potential myocardial ischemia: CFR values between 1.7 and 2.1 are associated with inducible myocardial ischemia.
• Endothelial dysfunction: Low CFR can reflect impaired endothelial function, even in the absence of obstructive coronary artery disease.

Gould et al investigated the effects of gradual coronary artery constriction on resting and maximal coronary blood flow in dogs. Using an electromagnetic flowmeter and a micrometer-controlled mechanical occluder on the left circumflex coronary artery, they progressively constricted the artery and measured resting coronary flow and the response to stimuli increasing coronary blood flow. The latter was achieved through various methods to induce a hyperemic response mimicking exercise, including reactive hyperemia following brief coronary occlusions. The results of this study remain a fundamental basis for understanding coronary physiology and form part of the underlying rationale for myocardial perfusion imaging. Their findings demonstrated that resting flow remains normal until severe stenosis (85-90% narrowing), while maximal flow begins to decrease with milder stenosis (around 45-50%), providing the physiological basis for stress myocardial perfusion imaging techniques used today. Gould et al. found the following:

• Resting coronary blood flow was not affected until the artery was constricted by at least 85%.
  • Interpretation: Individuals with stable coronary stenosis typically do not experience symptoms at rest unless the arterial narrowing is very severe (>85-90%).
• There was a significant correlation between the degree of coronary obstruction and the impairment of hyperemic response (i.e. the ability to increase coronary flow). A 45% obstruction resulted in a blunting of the hyperemic response, indicating a reduced capacity for coronary vasodilation. Further, a 90% stenosis abolished the hyperemic response.
  • Interpretation: Stenotic coronary arteries can maintain sufficient blood flow during resting conditions; however, as the degree of narrowing increases, the capacity to enhance flow during stress diminishes, to the extent that it is abolished in the setting of severe narrowing.
• Regional myocardial flow distribution was normal at rest, even with 80 percent constriction of the left circumflex artery. However, after hyperemic stimulus, there was a marked increase in perfusion of the myocardium supplied by the normal left anterior descending coronary artery, whereas the myocardium supplied by the constricted left circumflex artery failed to show a comparable increase.
  • Interpration: Resting perfusion can be misleading even in the presence of significant stenosis, and therefore the myocardium must be stressed in order to reveal differences in myocardial perfusion.

These observations form the physiological basis for performing stress imaging. Under resting conditions, coronary autoregulation can maintain adequate blood flow even in regions supplied by stenotic arteries, preventing ischemia from being detected during rest imaging. However, during stress, the autoregulatory mechanisms become inadequate, enabling the detection of areas with impaired perfusion.