Background
Conventional single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) evaluates the presence, extent, and degree of myocardial ischemia or infarction (ie, flow-limiting defects). SPECT is a nuclear medicine topographic imaging technique that uses gamma rays. It is similar to conventional nuclear medicine planar imaging using gamma cameras; however, the computer in SPECT provides 3-dimensional (3D) images. SPECT is based on the flow-dependent and/or metabolism-dependent selective uptake of a radioactive tracer by functional myocardial tissue. This method was developed to evaluate myocardial perfusion and viability and is applied both at rest and after exercise or pharmacologic stress to assess inducible ischemia due to flow-limiting coronary stenoses.
MPI is widely used in patients with coronary artery disease, and reconstruction algorithms improve the diagnostic accuracy and image quality. Hybrid SPECT/CT scanning combines the 2 types of images and allows attenuation correction and reduction of scanning time. [1, 2, 3, 4, 5, 6]
The technique involves the intravenous injection of small amounts of radioactive tracer (gamma-emitting radioisotope), which is avidly taken up by the cardiomyocytes so that the initial myocardial tracer distribution is in proportion to the viable myocardium. The use of cadmium-zinc-telluride (CZT) has improved the performance of SPECT by improving detection sensitivity and spatial resolution, as well as reducing the radiation dose. [7, 8, 9] The CZT detector works as a semiconductor with direct conversion of gamma radiation to electric signal. [10]
The history of cardiac nuclear medicine dates back to 1973, which marked the introduction of the exercise stress-test myocardial scan by H. William Strauss [11] and the first application of thallium-201 myocardial perfusion imaging by Elliot Lebowitz. Since then, it has been increasingly used in clinical cardiology. Technical developments that have fueled this increase are single-photon emission tomographic (SPET) imaging, pharmacologic stress, and electrocardiogram (ECG)-gated imaging. ECG-gated SPECT images allow for the assessment of the global left ventricular ejection fraction (LVEF), regional wall motion, and regional wall thickening at rest in patients with documented stress-induced wall motion and perfusion abnormalities. [12, 13]
The underlying principle is that under conditions of stress, the diseased myocardium receives less blood flow than normal myocardium. SPECT imaging performed after stress reveals the distribution of the radiopharmaceutical and, therefore, the relative blood flow to the different regions of the myocardium. Comparing stress images to a further set of images obtained at rest aids in diagnosis.
Images taken during dynamic exercise or pharmacologically induced stress (using vasodilators such as adenosine or a beta-agonist such as dobutamine) and rest injections enable independent assessment of myocardial perfusion and viability.
(Note the summary figure and other images below.)
Device summary. To acquire single-photon emission computed tomography (SPECT) images, the patient lies still in a supine position, and the gamma camera is rotated around the patient. Courtesy of Patrick J. Lynch, Yale University.
Single-photon emission computed tomography (SPECT) images compared with illustrations of the heart from similar views. The SPECT images (bottom row) show the distribution of the tracer and therefore the relative blood flow to the different regions of the myocardium. The top rows are illustrations of the heart to compare with the SPECT images from similar views. Notice there are more enhancements in the area that corresponds to the left ventricle because of its greater thickness. Courtesy of Patrick J. Lynch, Yale University.
Planar imaging. The gamma camera detects the gamma rays emitted from the tracer, and the image of where the tracer is found in the organs is transmitted to the computer. In planar technique, the computer provides a 2-dimensional myocardial perfusion image. Courtesy of Patrick J. Lynch, Yale University.
SPECT imaging performed after stress. The upper row shows short-axis slices after pharmacologic stress; the lower row shows the same slices when the body is at rest in conventional cardiac SPECT with Tc-99m tetrofosmin as a radiotracer. Arrows indicate a small perfusion defect on the backside of the heart (visible only on the stress images), showing ischemia in this region of the heart wall. Courtesy of Philipp A Kaufmann, MD, and Oliver Gämperli, MD, University Hospital Zurich.
Patient consent
In the area of medicolegal protection, an informed consent to performa exercise testing must be obtained. A detailed explanation of the procedures, procedure planning, and the indication for the test should be provided. The health care professional obtaining consent should also outline the possible adverse effects and complications.
Analysis
According to the American Society of Nuclear Cardiology, SPECT myocardial perfusion images should be analyzed as follows [14, 15] :
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Evaluate the raw images or the reconstructed maximum intensity projection image in cine mode, and review of sinogram and linogram images, to determine the presence of potential sources of image artifact and the distribution of extracardiac tracer activity.
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Interpret images with respect to the location, size, severity, and reversibility of perfusion defects, as well as cardiac chamber sizes, and the presence or absence of increased pulmonary uptake (especially 201Tl).
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Evaluate results of quantitative perfusion analysis.
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Evaluate functional data obtained from gated images.
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Consider the clinical data, stress ECG, and hemodynamic data that may influence the final interpretation of the study.
Indications
In patients who present with acute, stable chest pain, SPECT has been shown to be more cost-effective than any other diagnostic modality to date [16] and more accurate than exercise ECG in detecting myocardial ischemia. Special indications include determination of the hemodynamic significance of anomalous coronary arteries [17] and muscle bridging [18] and coronary aneurisms in the setting of Kawasaki disease. [19]
Inferior and posterior abnormalities and small areas of infarction can be identified, as well as the occluded blood vessels and the mass of infarcted and viable myocardium.
In patients with known coronary artery disease, SPECT has been proven to be a powerful technique in predicting the likelihood of future cardiac events. [20]
In assessing viable myocardium in a specific coronary artery distribution after a heart attack, stress images in SPECT may help determine the degree of inducible ischemia or viable myocardium amenable to revascularization. [21, 22, 23]
Contraindications
Absolute contraindications to dynamic exercise include the following:
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In patients with non-ST-segment elevation acute coronary syndrome or unstable angina, once stabilized, exercise stress can be considered 24-72 hours after chest pain, depending on clinically assessed risk. [24] ST-segment elevation myocardial infarction (MI) within the previous 4 days. [25]
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Left main coronary artery stenosis that is likely to be hemodynamically significant; left ventricular failure with symptoms at rest; recent history of life-threatening arrhythmias; severe dynamic or fixed left ventricular outflow tract obstruction (aortic stenosis and obstructive hypertrophic cardiomyopathy); severe systemic hypertension (systolic blood pressure > 220 mm Hg and/or diastolic blood pressure >120 mm Hg); recent pulmonary embolism or infarction, thrombophlebitis, or active deep vein thrombosis; and active endocarditis, myocarditis, or pericarditis are absolute contraindications. [26]
Relative contraindications to dynamic exercise include the following:
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Left bundle branch block (LBBB), bifascicular block, and ventricular paced rhythms (because dynamic exercise leads to perfusion abnormalities of the septum and adjacent walls in the absence of obstructive coronary disease) [27]
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Inability or poor motivation to perform dynamic exercise
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Recent exercise ECG that failed to achieve an acceptable workload (≥85% of the maximum predicted heart rate)
Absolute contraindications to vasodilator stress include the following:
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Recent acute coronary syndrome is a contraindication. Once stabilized, stress with vasodilators can be considered 24-72 hours after chest pain, depending on clinically assessed risk. [24]
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Suspected or known severe bronchospasm, second-degree and third-degree atrioventricular block in the absence of a functioning pacemaker, sick sinus syndrome in the absence of a functioning pacemaker, hypotension (systolic blood pressure < 90 mm Hg), and xanthine intake in the last 12 hours, or dipyridamole use in the last 24 hours are contraindications. [28]
Relative contraindications to vasodilator stress include the following:
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Bradycardia of less than 40 beats/min: Initial dynamic exercises normally increases the rate sufficiently to start the infusion. [28]
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Recent cerebral ischemia or infarction
Absolute contraindications to dobutamine stress include the following:
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Same as for dynamic exercise
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Known hypokalemia [29]
Relative contraindications to dobutamine stress include left bundle branch block, bifascicular block, and paced rhythm, for the same reason as for dynamic exercise.
Technical Considerations
Radiation exposure
Myocardial perfusion imaging has the highest average effective dose (15.6 mSv) and the highest percentage (22.1%) of all effective doses compared with other major radiologic procedures, including CT studies. [30] Low-dose ionizing radiation has been linked with up to 2% of solid cancers and leukemia. A small but cumulative danger from radiation due to SPECT is noted. However, radioactive tracers such as rubidium-82 reduce the radiation dose to the patient by a factor of 10 compared to technetium-99m. A complete myocardial perfusion examination with a dose less than 3 mSv may be achieved in the future. [31, 32]
According to a study by Einstein et al, compared with standard Anger SPECT (A-SPECT) cameras, high-efficiency (HE) cameras with specialized collimators and solid-state cadmium-zinc-telluride detectors offer the potential to maintain image quality while reducing the radiation dose. They found that ultra-low-dose high-efficiency SPECT (ULD HE SPECT) rest imaging correlates highly with standard-low-dose (SLD) A-SPECT. ULD HE SPECT was shown to have improved image quality, to have comparable extracardiac activity, and to achieve radiation dose reduction to 1 mSv for a single injection. [33]
In a Netherlands study of 24 patients who underwent clinically indicated myocardial perfusion imaging with cadmium zinc telluride (CZT) SPECT and a body weight-dependent (3 MBq/kg) technetium-99m-tetrofosmiin tracer dose, differences in segmental uptake values, ejection fraction, and end-diastolic volume were greater for shorter scans than for the 8-minute reference scan. Six minutes was the shortest acquisition time in stress MPI that did not affect the diagnostic value for a tracer dose of 3 MBq/kg. [34] On average, the diagnostic value was influenced in 7.7 segments per patient using the 2-minute scans, in comparison to 2.0 and 0.8 segments per patient using the 4- and 6-minute scans, respectively. In addition, the 4-min scans led to a significantly reduced image quality compared to the 8-min scans (P< 0.05). This was not the case for the 6-minute scan. [34]
The use of a hybrid CZT SPECT/64-slice CT system for dose reduction was studied to determine maximal degree of dose reduction without compromising image quality and quantification precision of clinical MPS. Ultra-low dose (< 190 MBq) myocardial perfusion imaging, even with short imaging times (< 6 min), was found to be feasible using a hybrid CZT SPECT/CT camera without compromising image quality or significantly altering quantification of myocardial perfusion or LV function. [35]
According to the authors, an additional 50% reduction of current low-dose recommendations from American Society of Nuclear Cardiology (ASNC) guidelines for 99mTc-labeled myocardial perfusion imaging is highly feasible while retaining short imaging protocols. For patients of normal MPS, there were no differences in defect size (DS), LV volumes, and ejection fraction (EF), regardless of 50% or 75% dose reduction. For patients of abnormal MPS, at 50% dose reduction, there was a significant difference in global DS but not in regional DS in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) regions. At 75% dose reduction, however, the difference was statistically significant in all areas, including global DS. Nonetheless, differences in the DS were minimal. The LV end-diastolic and end-systolic volumes and LVEF were not significantly different, regardless of 50% or 75% DR. [35]
Allergic potential to radiocontrast
Contrary to the risk of radiocontrast-induced allergy seen in CT angiography and coronary angiography, SPECT has a small risk of dye allergy. This is because in SPECT the radioisotopes used are in nanomole quantities and the vehicle used is normal saline. No known adverse reactions to the chemical molecules are recognized (sestamibi or tetrofosmin).
Other considerations
The presence of a healthcare professional that is up-to-date with basic life support is required for the duration of all stress procedures. Personnel trained in advanced life support should be rapidly available. Emergency equipment, drugs, and support personnel should also be available.
Outcomes
The incidence of fatal myocardial infarction/cardiac death in patients undergoing stress for myocardial perfusion imaging for exercise, dobutamine, [36, 37] dipyridamole, [38] or adenosine [39] has been shown to be 0.01, 0.0, 0.05 and 0.0%, respectively. [39] The incidence of nonfatal myocardial infarction/major cardiac complication in patients undergoing stress for myocardial perfusion imaging for exercise, dobutamine, dipyridamole, or adenosine has been shown to be 0.02, 0.3, 0.05 and 0.1%, respectively. [36, 37, 38, 40, 39]
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Device summary. To acquire single-photon emission computed tomography (SPECT) images, the patient lies still in a supine position, and the gamma camera is rotated around the patient. Courtesy of Patrick J. Lynch, Yale University.
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Single-photon emission computed tomography (SPECT) images compared with illustrations of the heart from similar views. The SPECT images (bottom row) show the distribution of the tracer and therefore the relative blood flow to the different regions of the myocardium. The top rows are illustrations of the heart to compare with the SPECT images from similar views. Notice there are more enhancements in the area that corresponds to the left ventricle because of its greater thickness. Courtesy of Patrick J. Lynch, Yale University.
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Planar imaging. The gamma camera detects the gamma rays emitted from the tracer, and the image of where the tracer is found in the organs is transmitted to the computer. In planar technique, the computer provides a 2-dimensional myocardial perfusion image. Courtesy of Patrick J. Lynch, Yale University.
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SPECT imaging performed after stress. The upper row shows short-axis slices after pharmacologic stress; the lower row shows the same slices when the body is at rest in conventional cardiac SPECT with Tc-99m tetrofosmin as a radiotracer. Arrows indicate a small perfusion defect on the backside of the heart (visible only on the stress images), showing ischemia in this region of the heart wall. Courtesy of Philipp A Kaufmann, MD, and Oliver Gämperli, MD, University Hospital Zurich.
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Positioning. The patient should be supine with both arms above the head. Courtesy of Philips Healthcare.
