Introduction

Myocardial perfusion scanning plays a significant role in diagnostic and therapeutic decision making in cardiac disease. These refer to a group of non-invasive imaging tests that can be performed to help clinicians assess blood flow to areas of myocardium. Obtaining information on perfusion and metabolite uptake from myocardium plays a vital role in determining the appropriate medical treatment or intervention for optimizing one's cardiac health. These tests are useful for diagnostic and prognostic purposes throughout a variety of clinical settings, including evaluating symptoms concerning for angina, to rule out acute coronary syndrome as a cause of chest pain, assessing therapeutic outcome after interventions, as well as for assessing for viable or scarred myocardium. With such information, clinicians can appropriately understand a patient's coronary health, perform risk stratification for future cardiovascular events, assess for therapeutic response to interventions correcting perfusion defects, and allow for prognostication.

Perfusion scanning utilizes various radiotracers, which are administered to the patient and allowed to distribute to multiple tissues. These radiotracers emit photons, which are detectable with a gamma camera which typically contains a single sodium iodide crystal (Single photon emission computed tomography, or SPECT) or multiple crystals (typically used in positron emission tomography, or PET) to interact with captured photons. These cameras contain a collimator, which helps eliminate background, and a photomultiplier, which translate the interactions between the photon and crystals into electrical energy to produce images.[1] In SPECT imaging techniques, common radiotracers used include thallium-201 or technetium-based radiotracers, including technetium-99m sestamibi or technetium-99m tetrofosmin.[2] Thallium-201 is distributed actively into myocardial cells, whereas technetium-based products are distributed passively depending on blood flow and myocardial viability.[2][3] These radiotracers are injected when the heart is stressed, either by exercise or pharmacologically. The uptake of radiotracer indicates areas of perfusion and viable tissue during stress and at rest. Areas of poor perfusion display improved perfusion during rest, termed reversible ischemia.[2]

SPECT, which is more commonly used and available in clinical practice today, uses planar images to reconstruct a three-dimensional representation of myocardial perfusion. Unlike planar imaging, SPECT can obtain sequential slices without overlap of normal and abnormal areas with improved resolution over planar imaging [4].  SPECT imaging has undergone validation in multiple large scale studies for detection of coronary artery disease; however, there are some limitations to this imaging modality.[5][6] These include artifacts such as those caused by motion, attenuation, or extracardiac activity affecting the quality of images and reader variability.[7] Also, SPECT imaging typically uses technetium-99m tracers, which have low first-pass extraction, and thus leading to the underestimation of ischemic changes both in extent and severity.[8]

PET imaging, although less available than SPECT, can help overcome some of these limitations. PET images have better spatial resolution and allow for attenuation correction more accuracy than SPECT.[9] With the high temporal resolution, PET scanning also allows for quantification of myocardial blood flow and myocardial flow reserve and can be of great utility in risk stratification in assessing cardiovascular mortality.[9][10] Further, PET imaging has the advantages of protocols requiring less time, less radiation exposure compared to SPECT imaging techniques.[11] In PET imaging, radiotracers such as ammonia N-13, rubidium-82, and flurpiridaz F-18 are radiotracers used in for myocardial perfusion imaging. Rubidium-82 is used commonly and can produce good quality images as it has a 65% myocardial extraction rate. In contrast, ammonia N-13 and fluripiridaz F-18 have a myocardial extraction rate of 80% and 95% respectively, therefore producing better quality images with higher resolution. The downside of the later radiotracers is the need for an on-site cyclotron.[9] Rubidium-82 is usable for pharmacologic stress testing, whereas ammonia-N-13 and flurpiridaz F-18 can be used for both exercise and pharmacologic stress testing.[9]

To obtain stress images, exercise or pharmacologic testing can is an option. Common pharmacologic agents used include regadenoson, adenosine, and dipyridamole. All three medications work by causing coronary vasodilatation, with subsequent blood flow differences. Adenosine and dipyridamole are A-2A as well as A-1, A-2B, and A-3 receptor agonists, which can also cause bronchospasm, AV nodal block, chest tightness, and flushing. Regadenoson is a selective A-2A agonist which can be a choice in patients with known bronchospasms.[9] Thus, regadenoson is the most common pharmacological agent used in clinical practice. 

Procedures

SPECT Imaging:

There are multiple protocols for obtaining SPECT imaging to assess myocardial perfusion and tissue viability. No single protocol is useful for every patient, and the studies require individualization for each patient depending on the diagnostic information desired by the clinician and patient characteristics. The most common radiotracers used in SPECT imaging include technetium-99m and thallium-201. Below are two examples of protocols used in SPECT imaging[12]:

Technetium-99m (Tc-99m) one-day rest-stress imaging protocol

1. Tc-99m radiotracer is injected intravenously.
2. 30 to 60 minutes later, resting myocardial perfusion images are obtained.
3. Depending on availability and patient characteristics, a vasodilator (pharmacologic stress) is administered (either dipyridamole 0.56 mg/kg, adenosine 140 mcg/kg/min for a 6-minute infusion, or regadenoson 0.4 mg injection). A second dose of radiotracer is also administered.
4. 15 to 45 minutes later stress images are obtained.
5. Rest and stress images are ready for review and interpretation by a trained professional.

Thallium-201 (Tl-201) Stress-Rest Redistribution imaging protocol

1. Depending on availability and patient characteristics, a vasodilator (pharmacologic stress) is administered (either dipyridamole 0.56 mg/kg, adenosine 140 mcg/kg/min for a 6-minute infusion, or regadenoson 0.4 mg IV) along with a Tl-201 radiotracer.
2. After 15 minutes, stress images are obtained and reviewed.
3. Depending on image interpretation an optional rest image is obtained 2.5-4 hours later, or 24 hours after initial radiotracer administration.
4. Images are ready for interpretation and determination of areas of poor myocardial perfusion and/or viability (if redistribution images were obtained at a later time).

PET Imaging: 

Procedures for PET CT scanning are similar to SPECT. One such protocol is described below[13]:

1. 60 mCi of Rubidium-82 chloride is infused in 50 ml of normal saline solution over 25 seconds.
2. Ninety seconds after infusion, rest images are obtained.
3. A vasodilator is administered (dipyridamole at 0.57/mg/kg for 4 minutes or regadenoson 0.4 mg given over 10 seconds followed by a 5-ml saline flush).
4. If using dipyridamole:
   1. A waiting period of 3 minutes  
   2. Start of rubidium 82 chloride infusion in 50 ml over 25 seconds
5. If using regadenoson:
   1. The rubidium 82 chloride infusion in 50 ml is started immediately after the saline flush
6. Images are obtained approximately 90 seconds after completion of the rubidium-82 infusion.

Indications

The use of myocardial perfusion imaging depends on the clinical context and suspicion of myocardial mal-perfusion or to assess response after an intervention. Of course, imaging itself does not substitute for one's clinical suspicion for myocardial ischemia. Some indications for myocardial perfusion imaging include[14]:

1. Evaluation of possible coronary artery disease for non-cardiac perioperative risk assessment (depending on surgical risk and medical comorbidities)
2. Detection of coronary artery disease (depending on clinical evidence, there are different indications, e.g., troponin elevation without history concerning for angina)
3. New diagnosis of heart failure with reduced left ventricular systolic function without an ischemic equivalent and no plan for coronary angiography
4. Ventricular tachycardia with a high risk of coronary artery disease
5. Syncope with intermediate to high risk of coronary artery disease
6. Prior non-invasive evaluation with indeterminate results where obstructive CAD remains a concern
7. New or worsening symptoms of angina in a patient with known CAD
8.  Risk assessment in post-revascularization for ischemic equivalent symptoms of chest pain, incomplete revascularization in an asymptomatic individual, or 5 or more years after coronary artery bypass grafting (CABG)
9. Assessment of myocardial viability to determine if a patient is a candidate for revascularization

Potential Diagnosis

With the use of myocardial perfusion imaging such as SPECT or PET, diagnosis of coronary artery disease can be made along with information of the extent and viability of myocardial tissue.

Normal and Critical Findings

Images are taken in various cuts along the short axis, vertical and horizontal long axes, and transaxial views. Pictures are taken with rest and during stress as described above. Areas with poor myocardium perfusion have less radiotracer uptake, whereas areas with adequate perfusion light up brightly on the images. The comparison of rest and stress images can help differentiate areas of viable, reversible areas of perfusion defects from those areas of non-reversible perfusion defects. This visualization helps in the decision regarding whether or not revascularization is needed.

Interfering Factors

SPECT imaging perfusion images are more prone to artifacts. Examples of artifacts that can interfere with SPECT imaging include patient motion during the study, interference from extra-cardiac activity, photon attenuation (e.x. from breast tissue or diaphragm), and attenuation map misalignment. Before quantitative analysis of the images, correction of motion and attenuation could minimize artifact. Other methods of minimizing artifact include supine and prone positioning.[7][9]

PET perfusion imaging techniques have better spatial resolution than SPECT. Therefore attenuation correction can occur more accurately.[7]

Patient Safety and Education

Patients should receive counseling regarding the risk of radiation exposure through myocardial perfusion imaging protocols. Radiation exposure typically is more in SPECT than in PET imaging. In SPECT imaging radiation dose can range from 10 to 20 mSv depending on the agent and protocol used (one day vs. two-day stress imaging). Agents used commonly used in PET imaging expose patients to less radiation especially, rubidium-82 and nitrogen-13 ammonia with typically less than 10 mSv of exposure.[9]

Clinical Significance

Myocardial perfusion scanning plays a major role in diagnostic and therapeutic decision making in cardiac disease. These refer to a group of non-invasive imaging tests that can be performed to help clinicians assess blood flow to areas of myocardium. Obtaining information on perfusion and metabolite uptake from myocardium plays a vital role in determining the appropriate medical treatment or intervention for optimizing one's cardiac health. These tests are useful for diagnostic and prognostic purposes throughout a variety of clinical settings, including evaluating symptoms concerning for angina, to rule out acute coronary syndrome as a cause of chest pain, assessing therapeutic outcome after interventions, as well as for assessing for viable or scarred myocardium.