Residency · Residency · Nuclear Medicine

Myocardial Perfusion SPECT: Acquisition and Interpretation

Radiopharmaceuticals for MPI

Tc-99m Sestamibi (Cardiolite)

Tc-99m sestamibi is a lipophilic cation that enters myocytes by passive diffusion driven by the mitochondrial membrane potential. Its first-pass extraction fraction is approximately 65% at rest but decreases at higher flow rates, a phenomenon known as extraction roll-off. Once inside the myocyte, sestamibi shows minimal redistribution, meaning the distribution it achieves shortly after injection is essentially fixed. It is excreted through the hepatobiliary system, so liver and subdiaphragmatic bowel activity can interfere with cardiac imaging. For this reason, a delay of 30 to 60 minutes after rest injection and 15 to 30 minutes after exercise injection is allowed for hepatic clearance before imaging.

Tc-99m Tetrofosmin (Myoview)

Tc-99m tetrofosmin has a similar mechanism to sestamibi, functioning as a lipophilic cation taken up by mitochondria. Its first-pass extraction is slightly lower at approximately 54%, and like sestamibi, extraction decreases at high flow rates, which can limit detection of mild stenoses. Tetrofosmin offers faster hepatic clearance than sestamibi, allowing a shorter wait time before imaging. Overall image quality and diagnostic accuracy are similar to sestamibi.

Thallium-201 (Tl-201)

Thallium-201 is a potassium analog that enters cells via the Na+/K+-ATPase pump. It has a higher first-pass extraction of approximately 85%, making it better at tracking flow at high flow rates compared to Tc-99m agents. The distinguishing feature of Tl-201 is that it redistributes over time: the initial distribution is proportional to blood flow, but over 3 to 4 hours, thallium redistributes into ischemic but viable myocardium, enabling a stress-redistribution protocol for viability assessment. The disadvantages of Tl-201 are significant: a longer half-life (73 hours), lower photon energy (69 to 83 keV) that produces more attenuation and scatter, and a higher patient radiation dose of approximately 15 to 20 mSv. These limitations have led to Tl-201 being largely replaced by Tc-99m agents for routine MPI, though it retains a role in viability assessment at some centers.

Imaging Protocols

One-Day Tc-99m Protocol

The one-day protocol can be performed as either a rest-stress or stress-rest sequence. In the rest-stress approach, a low dose (8 to 12 mCi) is injected at rest, followed by a high dose (24 to 36 mCi) at stress, with the higher stress dose overcoming the residual activity ("shine-through") from the rest injection. The stress dose is typically three times the rest dose. In the stress-rest approach, the high dose is given at stress first, and if the stress images are normal, the rest study may be omitted entirely. Total imaging time is 3 to 5 hours.

Two-Day Tc-99m Protocol

In the two-day protocol, a full dose (20 to 30 mCi) is administered for each injection on separate days. This approach provides better image quality because there is no shine-through from a prior injection, but it is less convenient for patients. It is used when optimal image quality is critical.

Stress-Only Protocol

The stress-only protocol involves performing stress imaging first and omitting the rest study if stress images are definitively normal. This reduces the radiation dose by approximately 50% and saves considerable time. If stress images are abnormal, the patient returns for rest imaging on the same day or the next day. Confident interpretation of a normal stress-only study typically requires attenuation correction or prone imaging. This approach is increasingly advocated for radiation dose reduction.

Tl-201 Stress-Redistribution Protocol

Tl-201 is injected at peak stress, and images are acquired immediately (stress images). The patient is reimaged at 3 to 4 hours, during which ischemic but viable tissue fills in with redistributed thallium. If a persistent defect remains, a small additional dose of Tl-201 can be reinjected to enhance viability detection. This protocol is rarely used now except for viability assessment.

Dual-Isotope Protocol

The dual-isotope protocol uses Tl-201 at rest and a Tc-99m agent at stress, acquired in separate energy windows. While it shortens the overall protocol by eliminating the wait between rest and stress injections, the higher radiation dose from Tl-201 has led to this protocol being largely abandoned.

SPECT Acquisition

Detector Configuration

Cardiac SPECT is typically acquired with a dual-head gamma camera with detectors positioned at 90 degrees (L-mode) or 180 degrees. The acquisition arc spans 180 degrees from 45-degree right anterior oblique to 45-degree left posterior oblique, optimized for cardiac imaging. The camera acquires 60 to 64 projections over this arc using either step-and-shoot or continuous rotation, with approximately 20 to 25 seconds per projection. A low-energy high-resolution (LEHR) collimator is used for Tc-99m.

Gated SPECT

ECG-gated SPECT divides the cardiac cycle into 8 or 16 frames, with each frame representing a specific phase. This enables assessment of left ventricular ejection fraction (LVEF), regional wall motion (normal, hypokinesis, akinesis, or dyskinesis), wall thickening (normal myocardium thickens during systole while scar does not), and end-diastolic and end-systolic volumes. Gated analysis is essential for differentiating true perfusion defects from artifacts: if a perfusion defect has normal wall motion and thickening, it is most likely an attenuation artifact rather than real disease.

CZT (Cadmium-Zinc-Telluride) Cameras

CZT cameras use solid-state semiconductor detectors instead of the traditional NaI(Tl) crystal and photomultiplier tube combination. Multiple fixed detector columns are focused on the heart, providing 2 to 5 times higher sensitivity, improved energy resolution, and dramatically faster acquisition times (5 to 7 minutes versus 15 to 20 minutes). These advantages allow lower administered doses, reducing patient radiation exposure. CZT cameras are increasingly being adopted for dedicated cardiac imaging.

Attenuation Artifacts

Common Artifacts

Attenuation artifacts are the most frequent interpretation pitfall in cardiac SPECT. In women, breast tissue attenuates photons from the anterior wall, creating an apparent anterior or anteroseptal perfusion defect. In men, the diaphragm and abdominal contents attenuate photons from the inferior wall, producing an apparent inferior defect. Large body habitus can cause lateral wall attenuation in either sex.

Methods to Reduce Attenuation Artifacts

CT-based attenuation correction (CTAC) is the most reliable method and is standard on SPECT/CT systems. Prone imaging shifts the heart away from the diaphragm; an inferior defect present on supine imaging that resolves on prone imaging is artifactual. Gated analysis provides another safeguard: attenuation artifacts show normal wall motion and thickening, while true perfusion defects from ischemia or scar may demonstrate wall motion abnormalities. Combined supine and prone imaging offers complementary assessment.

Image Interpretation

Standard Display

Myocardial perfusion SPECT images are displayed in three standard orientations. The short axis (SA) slices the heart perpendicular to its long axis, displaying all walls in a "donut" shape. The vertical long axis (VLA) provides a sagittal view showing the anterior and inferior walls. The horizontal long axis (HLA) provides a coronal view showing the septal and lateral walls. Stress images are displayed on top with rest images on the bottom, and corresponding slices are compared side by side.

17-Segment Model

The standardized AHA/ACC 17-segment model divides the left ventricle into a basal ring (6 segments: anterior, anteroseptal, inferoseptal, inferior, inferolateral, anterolateral), a mid ring (6 segments with the same territories), an apical ring (4 segments: anterior, septal, inferior, lateral), and the true apex (1 segment). Each segment is assigned to a coronary artery territory: the LAD supplies the anterior wall, anteroseptum, and apex; the RCA supplies the inferior wall and basal/mid inferoseptum; and the LCx supplies the lateral wall and inferolateral segments.

Perfusion Scoring

Semiquantitative Visual Score

Each segment is scored from 0 (normal perfusion) to 4 (absent perfusion), with 1 representing mildly reduced, 2 moderately reduced, and 3 severely reduced perfusion. The Summed Stress Score (SSS) is the sum of all segment scores on stress images: below 4 is normal, 4 to 8 is mildly abnormal, 9 to 13 is moderately abnormal, and above 13 is severely abnormal. The Summed Rest Score (SRS) reflects the extent of scar, and the Summed Difference Score (SDS), calculated as SSS minus SRS, quantifies the extent of ischemia. An SDS of 2 or greater indicates ischemia, while an SDS of 7 or greater indicates moderate to severe ischemia.

Quantitative Analysis

Automated software compares patient data against sex-matched normal databases. Polar maps (bull's-eye plots) display perfusion normalized to the hottest segment, and blackout maps highlight segments falling below normal thresholds. Quantitative analysis reduces reader variability and is particularly useful for serial comparison.

Interpretation Patterns

A reversible defect -- present on stress but normalizing on rest -- indicates ischemia. A fixed defect -- present on both stress and rest -- indicates scar or infarction (though fixed defects can also represent artifacts). A partially reversible defect -- showing partial improvement from stress to rest -- indicates ischemia superimposed on scar (peri-infarct ischemia). Reverse redistribution, where a defect appears worse on rest than on stress, is uncommon and may represent a patent infarct-related artery or post-revascularization changes. Transient ischemic dilation (TID) occurs when the LV cavity appears larger on stress than on rest, a high-risk finding suggesting extensive subendocardial ischemia or balanced multivessel disease. Increased lung uptake on Tl-201 images indicates elevated LV filling pressure and is another high-risk finding.

High-Risk Findings

Several findings on MPI portend a poor prognosis and may warrant coronary angiography: large perfusion defects involving multiple coronary territories, transient ischemic dilation (TID ratio above 1.22 for Tc-99m agents), increased lung uptake on Tl-201 imaging, reduced post-stress LVEF (a drop of 5% or more from rest), a large fixed defect with severely reduced LVEF, and exercise-induced ST depression accompanying a large perfusion defect.

<image>A standard display of myocardial perfusion SPECT images showing stress (top row) and rest (bottom row) images in three orientations: short axis, vertical long axis, and horizontal long axis. Demonstrate a reversible perfusion defect in the LAD territory (anterior wall and apex) that is present on stress images and normalizes on rest images, indicating ischemia. Include a 17-segment polar map (bull's-eye plot) with the defect highlighted and coronary artery territory overlay (LAD, RCA, LCx).</image>

<image>A comparison panel showing common attenuation artifacts and their solutions. Panel A: anterior wall defect in a female patient due to breast attenuation on standard SPECT, resolved with CT attenuation correction. Panel B: inferior wall defect in a male patient due to diaphragmatic attenuation, resolved on prone imaging. For each, show the corresponding gated images demonstrating normal wall motion and thickening, confirming artifact rather than true perfusion defect.</image>

<image>An illustration of high-risk findings on myocardial perfusion SPECT. Show four panels: (1) transient ischemic dilation with the stress LV cavity appearing larger than rest, (2) multivessel perfusion defects involving LAD and RCA territories, (3) increased lung uptake on Tl-201 stress images compared to rest, and (4) post-stress LVEF drop on gated SPECT. Label each finding with its prognostic significance.</image>

Clinical Pearls

Gated SPECT is essential for every study. Normal wall motion and thickening in an area of apparent perfusion defect strongly suggests an attenuation artifact rather than true ischemia or scar.

Transient ischemic dilation (TID) is a critical high-risk finding: the LV cavity appears larger on stress than rest, suggesting subendocardial ischemia causing apparent cavity enlargement. This may indicate severe multivessel or left main disease even when individual perfusion defects appear modest.

Stress-only protocols can reduce radiation dose by approximately 50%. If stress images with attenuation correction are definitively normal, rest images add little incremental value.

Tc-99m agents have lower first-pass extraction than Tl-201, which means they are less sensitive to mild stenoses at high flow rates. This extraction roll-off effect can cause mild ischemia to be missed, particularly in the context of balanced multivessel disease.

Inferior attenuation artifact in men and anterior attenuation artifact in women are the most common interpretation pitfalls. CTAC, prone imaging, and gated analysis should be used systematically to differentiate artifact from true disease.

The summed difference score (SDS = SSS minus SRS) quantifies the amount of ischemia. An SDS of 7 or greater indicates moderate to severe ischemia, a threshold often used for recommending coronary angiography.

CZT cameras offer dramatically faster acquisition and lower patient doses and are transforming cardiac SPECT practice.

References

• Dorbala S, et al. SNMMI/ASNC/SCCT guideline for cardiac SPECT/CT and PET/CT 1.0. J Nucl Med. 2013;54(8):1485-1507.
• Henzlova MJ, et al. ASNC imaging guidelines for SPECT nuclear cardiology procedures. J Nucl Cardiol. 2016;23(3):606-639.
• Berman DS, et al. Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance. J Nucl Med. 2006;47(1):74-82.
• Iskandrian AE, Garcia EV, eds. Nuclear Cardiac Imaging: Principles and Applications. 5th ed. Oxford University Press; 2016.

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