Myocardial perfusion imaging (SPECT, PET)

Chapter 1: 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.

---

Chapter 2: Indications and contraindications for myocardial perfusion imaging

Indications for myocardial perfusion imaging

Diagnosis of coronary artery disease (CAD): Myocardial perfusion imaging can confirm or rule out CAD in patients with symptoms suggestive of CAD.

SPECT imaging is recommended as the initial study in patients with low to moderate risk of CAD.

In patients with a high to very high risk of CAD, invasive coronary angiography is the first-line option.

Coronary computerized tomography angiography (CCTA) is currently the first-line investigation for patients with low risk of CAD.

Risk stratification: Myocardial perfusion imaging is valuable for assessing the risk of future cardiac events in patients with known CAD or after myocardial infarction.

Assessing myocardial viability: Myocardial perfusion imaging can determine whether dysfunctional myocardium or myocardium supplied by a diseased vessel, is viable and could benefit from revascularization.

Evaluating the success of revascularization: Myocardial perfusion imaging can assess effectiveness of procedures such as coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

Contraindications for myocardial perfusion imaging

Exercise stress testing is contraindicated in patients with acute myocardial infarction, unstable angina, severe aortic stenosis, decompensated heart failure, and uncontrolled arrhythmias. Pharmacologic stress agents have specific contraindications:

Adenosine, Dipyridamole, Regadenoson: Should be avoided in patients with active bronchospasm, severe hypotension, or high-degree AV block. Caffeine and other methylxanthines, which antagonize adenosine receptors, should be avoided for at least 12 hours before testing.

Dobutamine: Contraindicated in patients with severe hypertension, unstable angina, and significant arrhythmias.

Absolute contraindications

Acute myocardial infarction (MI) within 48 hours

Ongoing unstable angina

Uncontrolled cardiac arrhythmia with hemodynamic compromise

Active endocarditis

Symptomatic severe aortic stenosis

Decompensated heart failure

Acute pulmonary embolism, pulmonary infarction, or deep vein thrombosis

Acute myocarditis or pericarditis

Acute aortic dissection

Physical disability that precludes safe and adequate testing

Relative contraindications

Known obstructive left main coronary artery stenosis

Moderate to severe aortic stenosis with uncertain relation to symptoms

Tachyarrhythmias with uncontrolled ventricular rates

Acquired advanced or complete heart block

Hypertrophic obstructive cardiomyopathy with severe resting gradient

Recent stroke or transient ischemic attack

Mental impairment with limited ability to cooperate

Resting hypertension with systolic or diastolic blood pressures >200/110 mmHg

Uncorrected medical conditions, such as significant anemia, important electrolyte imbalance, and hyperthyroidism

Systolic blood pressure <90 mmHg, with increased risk of hypotension in patients with autonomic dysfunction, hypovolemia, or severe coronary or valvular disease

Recent (<48 hours) use of dipyridamole or dipyridamole-containing medications

Ingestion of caffeinated foods or beverages within 12 hours prior to testing

(none)

---

Chapter 3: The ischemic cascade

The ischemic cascade

The ischemic cascade describes the sequence of events during myocardial ischemia, beginning with perfusion abnormalities and ultimately leading to chest pain (angina). Myocardial perfusion imaging techniques, such as SPECT and PET, can detect perfusion abnormalities early in this sequence, before mechanical dysfunction (i.e. left ventricular systolic or diastolic dysfunction) or electrical changes (ST-T changes on ECG) become apparent. In contrast, modalities like echocardiography and ECG typically identify ischemia at later stages, when functional or electrical alterations are evident. Subjective symptoms (i.e. chest pain) appear as the last event in the cascade. Thus, ischemic episodes may pass asymptomatically.

Importance of heart rate during myocardial perfusion imaging

It is generally accepted that achieving 85% of the age-adjusted maximum heart rate (MHR) is sufficient to provoke overt ischemic signs during stress testing (Bourque et al.). Thus, patients who undergo exercise stress testing must achieve at least 85% of the age-adjusted MHR. Heller et al. demonstrated the following, among patients with known coronary artery disease:

Achieving 85% of age-adjusted MHR resulted in myocardial perfusion defects in all patients,, anginal symptoms in 83%, and ECG changes in all patients.

Achieving 70% of age-adjusted MHR resulted in perfusion defects in 89% of patients, anginal symptoms in 26% and ECG changes in 47%.

---

Chapter 4: Physics of myocardial perfusion imaging (SPECT, PET): Radiotracers, perfusion, blood flow and viability

SPECT vs. PET

In SPECT (Single Photon Emission Computed Tomography), radiotracers emit gamma photons directly. These gamma rays are detected by gamma cameras to create tomographic images of the left ventricle.

In PET (Positron Emission Tomography), radiotracers emit positrons. When a positron collides with an electron, they annihilate each other, producing two gamma photons emitted in opposite directions. PET scanners detect these gamma rays to construct images with high spatial and temporal resolution. PET offers higher spatiotemporal quality, as compared with SPECT.

Quantification of blood flow using PET

Quantitative PET perfusion imaging offers precise measurements of myocardial blood flow in milliliters per minute per gram of tissue (mL/min/g). This technique excels in detecting balanced ischemia. Such ischemia, seen in multivessel disease, exists when all coronary arteries are equally compromised, leading to uniform perfusion that may appear deceptively normal on SPECT. Detecting multivessel disease requires quantification of absolute coronary blood flow. This is possible using PET scanners, which also allow for the evaluation of microvascular function.

For a radiotracer to be suitable for quantifying myocardial blood flow, its uptake by the myocardium must closely correlate with actual blood flow. An ideal tracer exhibits high extraction from blood to tissue and high retention, with a linear relationship between myocardial blood flow and measured tracer activity over a wide range (Murthy et al.). As evident in Figure 1, 15O-water is the only tracer with myocardial uptake linearly related to coronary blood flow. 15O-Water is an ideal tracer, with a short half-life (2 minutes), causing minimal radiation exposure. It is metabolically inert and diffuses freely across cell membranes, allowing for precise quantification of myocardial blood flow and assessment of coronary flow reserve. A single session can be used for performing both rest and stress images (Sogbein et al.).

Roll-off phenomenon

The roll-off phenomenon in myocardial perfusion imaging, illustrated in Figure X, highlights the non-linear relationship between tracer uptake and coronary blood flow. As observed with tracers such as technetium-99m and thallium-201, uptake increases linearly at low coronary flow rates. However, as flow continues to rise, tracer uptake plateaus. This saturation effect can lead to an underestimation of blood flow in regions affected by significant coronary artery disease, potentially resulting in false-negative findings.

Radiotracers in myocardial perfusion imaging

Radiotracers are designed to identify ischemic areas of the myocardium by highlighting regions with reduced blood flow.

Radiotracers for SPECT

Technetium-99m (Sestamibi or Tetrofosmin): With a six-hour half-life allowing high doses for better image quality. this tracer diffuses passively into cardiomyocytes, binding to mitochondria, with minimal redistribution.

Thallium-201: This is a potassium analog with a 73-hour half-life, entering cardiomyocytes via the Na+/K+ ATPase pump. It undergoes redistribution, making it suitable for assessing viability and hibernating myocardium, at the expense of higher radiation exposure and blurrier images. The absence of thallium uptake indicates non-viable myocardium, while redistribution into initially hypoperfused regions suggests viability.

What is myocardial redistribution?

In myocardial perfusion imaging, redistribution refers to the movement of a radiotracer within the myocardium over time. Radiotracers without redistribution maintain their initial distribution, meaning that the myocardial distribution of the tracers is fixed immediately after administration. Radiotracers with higher levels of redistribution can move from areas of higher concentration to regions with lower concentration, for reasons other than perfusion differences, making image interpretation more ambiguous.

Table 1. Radiotracers used for SPECT imaging

	Thallium-201	Technetium-99m
Radiotracer dose	3–4 mCiAdditional 1 mCi for reinjection protocol	30 mCi if resting10 + 30 mCi if both rest and stress imaging is performed
Radiation exposure	12–16 mSvT1/2 = 73 hr	10 mSvT1/2 = 6 hr
Study duration	4–5 hr (rest and redistribution)24 hr if additional imaging is performed	1–2 hr
Functional information	No	Yes
Redistribution	Yes – Needs repeat imaging to assess viability.	No – Perfusion is fixed at the time of injection.
Image quality	Inferior74-keV photonsLow energy photons, lower photon count (noise)	Superior140-keV photonsHigher energy photons, higher photon count (less noise)
Extracardiac activity	Frequent lung uptake may reduce image quality	Frequent liver and bowel uptake may delay acquisition or cause artifacts
Contraindications	None	Resting hypotensionInability to administer nitroglycerine
Extraction fraction	85% Thallium	65% Sestamibi54% Tetrofosmin
Clearance	Urinary/GI	Hepatobiliary

Tracers for PET imaging

Table 2. Radiotracers used for PET myocardial blood flow quantification

	82Rb-chloride	13N-ammonia	15O-water	18F-flurpiridaz
Isotope production method	Generator	Cyclotron	Cyclotron	Cyclotron
Isotope half-life (min)	1.27	10	2.0	110
Positron range (mm) RMS	2.6	0.57	1.0	0.23
Image resolution (mm) FWHM	8	5	6	5
Effective dose (mSv/GBq)	1	2	1	2
Spillover from adjacent organs	Stomach wall	Liver and lung	Liver	Early liver
Typical rest dose for 3D/2D (mCi†)	30/45	10/15	20/30	2/3
Typical stress dose for 3D/2D (mCi†)	30/45	10/15	20/30	6/7
Protocol features	Rapid protocol	Permits exercise; delay of 4–5 half-lives between rest and stress unless different doses used	Rapid protocol; no tracer retention for routine MPI	Permits exercise; different doses for rest and stress required

18F-Fluorodeoxyglucose (18F-FDG) PET

18F-Fluorodeoxyglucose (18F-FDG) PET is used for assessing myocardial viability. It is selectively taken up by metabolically active (viable) myocardium, enabling differentiation between viable and non-viable tissue. The primary utility is determining the extent of viable myocardium in regions with reduced perfusion or previous infarction. This information can guide decisions about revascularization procedures; revascularization is unlikely to provide any benefit if no viable myocardium is detected, and vice versa. 18F-FDG PET is the most sensitive imaging technique for identifying viable, hibernating myocardium. 18F-FDG PET is also used to diagnose cardiac sarcoidosis.

Coronary steal phenomenon

Vasodilator stress agents can also cause coronary steal, a phenomenon that occurs when blood is redirected from a region supplied by a stenotic artery to a region with better perfusion. This occurs because the diseased arteries are already maximally dilated at rest, whereas the healthy arteries can still dilate in response to pharmacologic agents. This redistribution of blood flow can exacerbate ischemia in already compromised areas.

Reverse distribution

Reverse redistribution refers to a phenomenon where a perfusion defect seen during stress imaging appears to worsen or is new on rest images. This pattern is sometimes seen with technetium-99m sestamibi and is thought to be an artifact rather than an indication of true pathology. Reverse redistribution is more common in obese patients (often affecting the RCA territory) and women with large breasts (typically in the LAD territory). It has no direct correlation with obstructive coronary artery disease and is generally considered a benign artifact.

---

Chapter 5: Pharmacologic agents in myocardial perfusion imaging

Indications for pharmacologic agents

Pharmacologic stress tests are indicated in the following scenarios:

Inability to exercise due to physical limitations.

Contraindications to exercise, such as unstable angina, severe aortic stenosis, decompensated heart failure, or aortic aneurysm.

Baseline ECG abnormalities rendering ST-T interpretation difficult, including left bundle branch block (LBBB) or pacemaker rhythms.

Atrial fibrillation or atrial flutter

Patients on medications such as nitrates, beta-blockers, or calcium channel blockers

Recent acute myocardial infarction (AMI)

Pharmacologic agents in perfusion imaging

Vasodilators (adenosine, dipyridamole, regadenoson)

These agents exert vasodilatory effects, increasing coronary blood flow by relaxing vascular smooth muscle. They are contraindicated in patients with bronchospastic lung disease, or a history of significant reactive airway disease. Contraindications also include second-degree or third-degree AV block, sinus node dysfunction without a pacemaker, systolic blood pressure below 90 mmHg, and known hypersensitivity to the agent. Aminophylline is the antidote for regadenoson toxicity.

Adenosine and regadenoson work primarily by activating A2A adenosine receptors, which leads to coronary vasodilation. This effect is more pronounced in healthy arteries, which can dilate more than stenotic arteries, which are already dilated. This results in flow heterogeneity and perfusion defects in areas supplied by the disease artery. Thus, vasodilators replicate the effects of exercise on coronary arteries, without the need for physical activity.

Advantages of regadenoson over adenosine

Regadenoson has advantages over adenosine:

Regadenoson is a selective A2A receptor agonist: A2A receptors are responsible for coronary vasodilation. This selectivity minimizes activation of A1, A2B, and A3 receptors, which are associated with adverse effects such as bronchoconstriction and atrioventricular block. Adenosine is an agonist on A1, A2A, A2B and A3 receptors.

Fixed-dose administration: Regadenoson dosing is not weight-based, simplifying administration.

Dipyridamole

Dipyridamole has multiple targets that contribute to its vasodilatory effects. It inhibits phosphodiesterases, particularly PDE3 and PDE5, which break down cAMP and cGMP. It also inhibits the cellular reuptake of adenosine into endothelial cells. Further, it inhibits adenosine deaminase, which is responsible for breaking down adenosine. These actions result in increased extracellular adenosine concentrations, causing vasodilation.

Dobutamine

Dobutamine is a chronotropic and inotropic agent. It increases heart rate, myocardial contractility, and blood pressure, thereby simulating the effects of exercise. However, dobutamine is rarely used in current practice due to its less favorable safety profile and the preference for vasodilators like adenosine, dipyridamole, and regadenoson, which are generally better tolerated and easier to administer.

(none)

---

Chapter 6: Interpretation of myocardial perfusion images (Myocardial SPECT / PET)

Interpreting myocardial perfusion SPECT images involves a systematic comparison of rest and stress images to assess myocardial ischemia and infarction. The key steps in this process are outlined below.

Image acquisition and evaluation

Stress Imaging: Initially performed using exercise or pharmacologic agents to elevate myocardial oxygen demand (or simulate increased demand using vasodilatory agents). A radiotracer is administered at peak stress to capture blood flow distribution under these conditions. If stress imaging results are entirely normal, further imaging may not be necessary.

Rest Imaging: Conducted after a predefined interval to allow for radiotracer clearance or with a different radiotracer to capture myocardial blood flow under baseline conditions.

Raw Image Analysis: Raw images are reviewed to identify potential artifacts, extracardiac tracer activity, and assess image quality and patient motion.

Alignment: Ensure proper alignment of rest and stress images to accurately compare corresponding myocardial regions, as misalignment can lead to incorrect interpretation of perfusion differences.

Perfusion assessment

The assessment of myocardial regions in myocardial perfusion imaging (MPI) is based on principles similar to those used in echocardiography. The 17-segment model of the left ventricle serves as a standardized framework for identifying and localizing areas of ischemia or infarction. This segmentation facilitates precise reporting and ensures consistent communication of findings across clinicians. Perfusion defects are categorized by their size, encompassing:

Small defects: <10% of the left ventricular myocardium.

Medium defects: 10–20% of the myocardium.

Large defects: >20% of the myocardium.

Perfusion defects are further classified based on the intensity of tracer uptake and associated myocardial changes:

Mild defects: Characterized by decreased tracer counts while preserving normal wall thickness, often indicative of early or mild ischemia.

Moderate defects: Associated with wall thinning, suggesting a more advanced level of ischemia or partial scarring.

Severe defects: Defined by absent tracer uptake, with signal intensity comparable to background activity, typically representing infarcted tissue or non-viable myocardium.

Perfusion patterns and reversibility

Perfusion patterns are systematically analyzed by comparing tracer uptake across all myocardial regions. Areas of reduced perfusion, which manifest as less intense or absent uptake, are identified and categorized. A critical aspect of this evaluation is the determination of reversibility, which involves comparing stress and rest images to distinguish between:

Reversible defects: Indicative of ischemia, where reduced perfusion during stress normalizes at rest.

Irreversible defects: Suggestive of infarction or scar tissue, where perfusion remains reduced under both conditions.

Reverse redistribution: A less common pattern where defects appear worse at rest than during stress, potentially indicating microvascular dysfunction or other pathologies.

The software allows for detailed regional analysis of myocardial perfusion, highlighting specific segments of the left ventricle that demonstrate abnormalities. These tools compare perfusion data to population-based reference databases, often adjusted for sex and age, to identify deviations from normal values. This enhances the ability to detect subtle perfusion defects and differentiate between normal and abnormal patterns.

Reverse redistribution (RR)

Reverse redistribution (RR) in SPECT myocardial perfusion imaging is an unusual phenomenon in which a perfusion defect becomes evident or worsens in rest images compared to stress images. This pattern contrasts with the typical expectation in myocardial perfusion imaging, where defects are more pronounced during stress.

RR is characterized by normal or near-normal perfusion observed during stress, followed by the appearance of a perfusion defect in rest images. It has been documented with thallium-201 and technetium-99m tracers (sestamibi and tetrofosmin). Approximately 5% of all SPECT studies exhibit RR, with a higher prevalence when using thallium tracers (Kashefi et al.).

The phenomenon is most commonly observed in regions supplied by the right coronary artery (RCA). Notably, RR often occurs in patients with normal epicardial coronary arteries, suggesting a possible association with microvascular dysfunction. The prognostic significance of reverse redistribution warrants further investigation, although it is considered an unfavorable prognostic marker (Swinkels et al).

Functional imaging of left ventricular function

ECG-gated myocardial perfusion imaging adds an important layer of information by allowing simultaneous evaluation of left ventricular function. This includes assessing wall motion and thickening in addition to perfusion, which can help differentiate between viable and non-viable myocardial tissue. Parameters such as ejection fraction, end-diastolic volume, and end-systolic volume can be quantified. SPECT measurements of LV volumes and ejection fraction (EF) show a high correlation with cardiac MRI measurements. There is, however, a tendency for SPECT to underestimate LV volumes compared to MRI, particularly in patients with dilated ventricles (van Derwall et al.).

Normal variants and artifacts

It is important to distinguish true perfusion abnormalities from normal variants or artifacts. Common normal variants include:

Apical thinning: Seen as a fixed perfusion defect in the apical inferior wall or septum with normal wall motion, often observed in both SPECT and PET imaging.

Basal lateral perfusion defect: Seen as a fixed defect in the basal lateral wall, particularly on 13N-ammonia PET/CT, with normal wall motion. This can be a normal finding.

Breast and diaphragmatic attenuation: Breast tissue or diaphragmatic attenuation can result in fixed perfusion defects in the anterior or inferior walls, respectively. These artifacts can often be differentiated by repeating the imaging in a prone position or using attenuation correction methods.

High-risk features in perfusion images

MPI provides significant prognostic information based on the presence of high-risk features. According to Table 18.4, high-risk features in MPI include:

Large perfusion defects: Large single or multi-territorial fixed and/or reversible perfusion defects involving more than 15% of the left ventricular (LV) mass suggest extensive coronary artery disease.

Transient ischemic dilation (TID): An apparent increase in the size of the LV cavity during stress compared to rest indicates extensive subendocardial ischemia and is a marker of multivessel or left main disease.

Stress-induced myocardial stunning: A drop in left ventricular ejection fraction (LVEF) post-stress suggests significant ischemia and is considered a high-risk finding.

Increased pulmonary or right ventricular tracer uptake: This indicates elevated left ventricular filling pressures during stress, reflecting increased risk.

Transient ischemic dilatation

Transient Ischemic Dilation (TID) is an apparent increase in the size of the LV cavity during stress compared to rest. TID is considered a marker of severe, often multivessel CAD, and is associated with a high risk of adverse cardiac events. TID can also occur as an artifact in patients with significant attenuation, such as those with obesity.

Increased lung uptake

Increased lung uptake of radiotracer during stress is another high-risk marker indicative of elevated left ventricular filling pressures and severe ischemia. It reflects impaired LV function and correlates with extensive CAD, including left main or multivessel disease. Increased lung uptake is often associated with transient ischemic dilation and other markers of poor prognosis.

Image interpretation

Normal SPECT scan, with anatomical relations depicted. Adapted from Myohan et al.

Normal SPECT results. Source: Abdelradi et al, Cureus. 2021 Jun 27;13(6):e15952. doi: 10.7759/cureus.15952.

Myocardial ischemia (reversible perfusion defects) at the apex, mid-basal anterolateral, mid-basal inferoseptal and apical-mid-basal inferior segments. Source: J Biomed Res. 2013 Sep 30;27(6):467–477. doi: 10.7555/JBR.27.20130135.

Lateral myocardial ischemia (arrows). Scan provided by Since Falastrum.

Anteroapical myocardial infarction. Scan provided by Since Falastrum.

SPECT perfusion images show minimal reversible ischemia in the basal anterior wall (32, 33), and the rest of the anterior wall (30, 31) showing a non-reversible perfusion defect (i.e. infarction). Source J Saudi Heart Assoc. 2010 Jul 14;22(3):157–158. doi: 10.1016/j.jsha.2010.04.004.

Normal scan in a patient with balanced ischemia. Source Cureus. 2024 Feb 7;16(2):e53789. doi: 10.7759/cureus.53789

Anterior wall ischemia (red arrows). Source.

---