SPECT Imaging

Anatomy and Physiology

The utility of the SPECT scan lies in its ability to provide detailed physiological information about the tissues. This is accomplished via producing and administering radioactive tracer compounds, also known as probes. These probes generally consist of a detectable (via gamma camera) radioactive isotope coupled with a biologically active ligand specific to the imaged tissue.[2] The most common isotopes used are technetium-99m (Tc), iodine-123, and, to a lesser extent, thallium-201. When selecting an isotope, the clinician must consider the goal of the scan, the risk to the patient, and the expense of the isotope itself. Tc has a half-life of 6 hours and high photon flux, leading to shorter scan times and lesser radiation exposure to the target organ. This allows for administering higher tracer doses, providing clear images without significantly increasing radiation exposure to the patient.[2]

On the other hand, iodine-123 has a much longer half-life of 13 hours, leading to a greater concentration of detectable iodine in the target organ compared to the background. However, the longer half-life and greater localized concentration of iodine-123 increase the radiation dose to the organ. Because of the short scan time, clear images, and low associated radiation dose, Tc is often the preferred isotope for most clinical applications. However, iodine isotopes are highly preferred for studies of iodine-consuming tissues such as the thyroid gland.[3]

While the isotope chosen by the clinician is important, SPECT imaging depends on more than just the selection of the correct radioisotope. The success of the SPECT scan requires the isotope to be successfully bound to a biologically active ligand, which interacts with the body tissues to deliver the isotope to the desired location. For example, Tc can be linked to a compound known as hexamethylpropyleneamine oxime (HMPAO), which can cross the blood-brain barrier and is taken up as a metabolic substrate by brain tissue. Since HMPAO uptake directly correlates with metabolic activity, cerebral SPECT studies can show areas of increased brain activity and anatomically normal but metabolically deranged brain tissue, which would otherwise not be seen on conventional imaging. This makes SPECT a useful modality in treating cerebral perfusion disorders and dementia.[4][5]

SPECT imaging has also found great utility in cardiovascular disease, particularly in assessing myocardial perfusion during stress testing. For this purpose, Tc is bound via a coordination complex to 6 methoxyisobutylisonitrile (MIBI) groups to form a tracer compound known as sestamibi. The lipophilic MIBI groups can cross myocardial capillary membranes and deliver Tc into the myocardium cells at a rate proportional to blood flow. This allows the clinician to diagnose, assess, and evaluate perfusion defects of the heart. The scan may also be linked to the patient’s heartbeat via electrocardiography, and this type of study is known as a multi-gated acquisition scan (MUGA). MUGA produces detailed information about the perfusion and functionality of the heart at different points of the cardiac cycle. Thallium was commonly used for myocardial SPECT but has been largely phased out in favor of Tc.

Indications

Indications for SPECT imaging are developed by imaging societies, and some important ones are listed below.[3] These indications include:

1. Evaluating patients with suspected dementia
2. Localizing epileptic foci preoperatively
3. Diagnosing encephalitis
4. Monitoring and assessing vascular spasm following subarachnoid hemorrhage
5. Mapping of brain perfusion during surgical interventions
6. Detecting and evaluating cerebrovascular disease
7. Predicting the prognosis of patients with cerebrovascular accidents
8. Corroborating the clinical impression of brain death
9. Several indications in the field of oncology are listed in this article.[1]

In addition, the American Society of Nuclear Cardiology has developed an extensive list of indications for cardiac SPECT studies.[6][7] Some notable indications include:

1. Evaluating patients for coronary artery disease.
2. Assessing treatment response and guidance of future therapy in coronary artery disease, cardiomyopathy, and heart failure patients.
3. Diagnosing coronary artery disease in patients unable to perform a standard exercise stress test.
4. Pre-surgical evaluation of patients with suspected or confirmed coronary artery disease.

SPECT scans are also indicated for non-cardiac and non-neurological conditions such as osteomyelitis, spondylolysis, parathyroid disease, pulmonary embolism, and abscess localization.

Contraindications

SPECT imaging alone has no absolute contraindications; however, patients may rarely experience allergic reactions to the tracer compound. Most often, contraindications for SPECT imaging are related to the underlying procedure rather than the SPECT scan itself. For example, a cardiac stress test augmented with SPECT carries the same risks and contraindications as a routine stress test. Clinicians should also carefully consider the risks of radiation exposure when referring patients who are pregnant for SPECT, and radioactive iodine isotopes should be avoided in these patients as well due to fetal iodine uptake.[8] Finally, some obese patients may exceed the weight limit of the scanner apparatus.

Equipment

3D-SPECT imaging requires a rotating multi-headed gamma camera, a collimator, and a radio-labeled tracer specific to the target tissue. The basic function of the camera is the detection of photons produced by gamma decay of the tracer compound, which is emitted in all directions from the patient. The collimator functions to filter these photons, allowing only particles that are parallel to the detector through. The collimator, therefore, focuses on the radiation, and collimator selection influences the sensitivity and resolution of the final image. The number of gamma camera heads increases the resolution of the final image and decreases the amount of time required for the scan. However, skilled medical physicists and nuclear radiologists can produce high-quality images with single-headed cameras.[3][9]

Personnel

The American College of Radiology offers technical standards for the roles and responsibilities of personnel involved in the safe and effective administration of a SPECT study. The personnel required for a safe and effective SPECT scan generally include:

1. Clinician
2. Nuclear medicine technologist
3. Nuclear pharmacist
4. Medical physicist
5. Radiation safety officer

A board-certified nuclear cardiologist or nuclear radiologist should be present to supervise the study.

Preparation

Patients should be instructed to avoid caffeinated beverages for at least 12 hours before the study. This is because caffeine interferes with the action of vasodilatory medications that may be administered during the study. Caffeine also affects cerebral blood flow and can negatively influence cerebral SPECT imaging. The patient should also avoid dipyridamole and other phosphodiesterase-3 inhibitors for at least 48 hours to avoid a synergistic vasodilatory effect, which may produce an unsafe drop in blood pressure.[10] Finally, all patients should be made nil per oral for at least 3 hours before the procedure and asked to void urine beforehand to maximize comfort.

Technique or Treatment

First, the patient is injected with a radio-labeled tracer compound selected by the nuclear pharmacist. For cerebral studies, the patient is first seated in a quiet, dimly lit room and asked not to read or speak for at least 10 minutes before tracer injection. If the patient requires sedation, it should be administered after the tracer. Following injection, there is a variable waiting period to allow the tracer to circulate and be taken up by the target tissues. This waiting period can be as long as 90 minutes for cerebral studies or as short as 15 minutes for cardiac stress tests. Wait periods for a particular study also vary depending on tracer selection and dose.

Once the waiting period has elapsed, the patient is moved into the detector apparatus. If the patient is undergoing cardiac stress testing, they are given cardiac stimulants such as atropine per standard stress testing protocols. Both cerebral and cardiac studies may utilize vasodilatory medications to assess tissue perfusion. Once the patient is in place and the necessary medications have been administered, the detector rotates around the patient, taking planar scans every 3 to 6 degrees, which are combined to produce the final 3D image. Specific imaging protocols vary and may require a single scan, as in brain imaging, or several scans may be taken at set timing intervals, as in stress/rest imaging for cardiac SPECT.[11] While SPECT can produce detailed information about the tissues, it has limitations. Small metabolic abnormalities that may be detected on SPECT are often difficult to localize without corresponding anatomical imaging. To avoid these difficulties, a combined SPECT/computed tomography protocol has been developed, wherein functional and anatomical abnormalities detected by the SPECT study are also imaged simultaneously on computed tomography.

Certain SPECT protocols that can be employed to reduce radiation exposure and hazards include the following:[12][13][14]

• Appropriate patient selection for SPECT imaging based on a clear indication reduces unnecessary radiation exposure to patients and prevents the possibility of an error.
• Technetium-99 m-based SPECT protocols (sestamibi and tetrofosmin) offer lower patient radiation exposure than thallium-201 (stress/redistribution and stress/reinjection) protocols. For the evaluation of chest pain and the diagnosis of ischemia, technetium-99 m-based protocols are safer and preferred.
• The radiotracer dose should be weight-based to optimize the required radioactivity dose.
• Cadmium zinc telluride detectors in the imaging camera are more sensitive to incident ionizing radiation, and these detectors have better energy and spatial resolution. Utilization of cadmium zinc telluride cameras and Anger cameras can optimize radiation techniques.
• SPECT stress-only protocols using technetium-99m labeled radiotracers may reduce radiation exposure by 25% compared to typical rest/stress studies. Stress-first imaging is advisable in good imaging subjects who do not have a high pretest probability of an abnormal study. This is particularly important and feasible in young patients, especially those with a low to moderate pretest probability of coronary artery disease.
• The 2-day rest/stress technetium-99m (14 mSv) can be optimized to either stress only (7 mSv) or single-day rest/stress protocols (10 mSv), thereby minimizing radiation exposure.
• Image acquisition practices can be optimized to lower the amount of required radioactivity. In cooperative patients, the radiotracer dose can be reduced by lengthening acquisition times. Positioning the camera as close to the patient as possible throughout the acquisition is important to lower the required radioactivity dose.
• Newly developed reconstruction algorithms can maintain image quality from SPECT studies despite reducing the radiotracer dose. Using a novel wide-beam reconstruction algorithm, superior image quality can be acquired with a 50% reduction in radiation dose.
• If a scanner utilizes a CT scan for attenuation correction, the acquisition protocol can be optimized for the lowest dose available (rod-source).
• Software developments like resolution-recovery techniques can reduce radiation exposure significantly.

Complications

The most common complications from the procedure are mild reactions to the vasodilators and other medications used during the test. These side effects include flushing, headache, GI distress, and lightheadedness. More severe side effects such as hypotension, arrhythmias, chest discomfort, or AV blockade may also be seen. Rarely, an allergic reaction to the tracer compound or study medications may occur. The healthcare team should also consider the risks of radiation exposure to the patient, particularly if the patient is pregnant or planning to become pregnant. A Tc stress/rest cardiac scan carries the greatest effective radiation dose at 11.8 mSv, while a Tc brain scan carries an effective dose of 5.7 mSv. The effective dose for most SPECT scans, excluding cardiac stress/rest studies, is usually below 10 mSv. By comparison, the effective radiation doses for head computed tomography, chest computed tomography, and computed tomography coronary angiography are 2.0, 7.0, and 16.0 mSv, respectively.[15]

Clinical Significance

In myocardial perfusion testing, SPECT has been shown to have a sensitivity of 82% and a specificity of 76% for the diagnosis of coronary artery disease. In addition, those patients with normal myocardial SPECT imaging have less than 1%  yearly risk of adverse cardiac events. Regarding cerebral imaging for the diagnosis of Alzheimer dementia, SPECT has a sensitivity of 92%, a specificity of 100%, a positive predictive value of 92%, and a negative predictive value of 57%.[10][16][17]

Enhancing Healthcare Team Outcomes

To optimize outcomes, the clinician should confirm that the patient has not consumed caffeine or phosphodiesterase-5 inhibitor medications within 12 to 24 hours of the test. The patient’s vital signs and oxygen saturation should be monitored, recorded, and reported to the team regularly by a dedicated clinician. Before the study begins, this clinician should ensure all necessary resuscitative equipment is fully functional in the imaging suite. For cardiac stress testing, the patient should be on a cardiac monitor with venous access established before the administration of atropine and other cardiac stimulants. The risk of radiation exposure to staff is low; however, radiological safety protocols should be made clear to all involved staff and strictly enforced by the designated radiation safety officer.[10]