Nuclear Stress Test (Myocardial Perfusion Imaging) Demystified -

Heart disease is scary. In fact, it is the leading cause of death in the United States. Coronary artery disease, the most common form of heart disease, accounted for 382,000 deaths in the United States in 2020 alone.

Even scarier, many people walk around with heart disease without even knowing it!

Fortunately, medicine has evolved to improve our ability to detect and treat heart disease. One such advancement is the nuclear stress test, also known as Myocardial Perfusion Imaging (MPI).

In this article, I’ll cover the basics of a cardiac stress test, what a nuclear medicine stress test is, why it’s performed, how it’s performed, and briefly discuss “negative” and “positive” test results.

Let’s start with a brief overview of coronary artery disease and why it matters. 

Heart Basics

The heart is a large muscle in the chest that acts as a pump to move blood throughout the body. Like all muscles, the heart requires oxygen and nutrients to function, with higher levels of activity requiring greater amounts of resources.

Nuclear Stress Test - Heart Anatomy and Flow v2

The heart consists of four chambers – two atria (top chambers) and two ventricles (bottom chambers). It can be thought of as two separate sides/pumps, right and left. The top chambers (atria) act as small pumps that fill the bottom chambers (ventricles). The ventricles are the larger/stronger pumps that pump blood throughout the body.

The right side of the heart pumps blood through the pulmonary arteries to the lungs, where the blood gets rid of carbon dioxide (CO2) and picks up oxygen (O2).

The blood returns to the left side of the heart, which then pumps the blood to the rest of the body, supplying all of the organs, muscles, etc., with oxygen and nutrients. The left ventricle pumps blood throughout the entire body – to your head, toes, and everything in between – and therefore is a larger/thicker muscle than the right ventricle because it has to pump blood a much longer distance.

What is Coronary Artery Disease?

The coronary arteries are the blood vessels that deliver oxygen and nutrients to the heart. The right coronary artery delivers blood to the right and back sides of the heart and the left coronary artery delivers blood to the left and front sides of the heart.

The left main coronary artery typically splits into a “left anterior descending” coronary artery that supplies the front and left sides of the heart and a “circumflex” coronary artery that wraps around to the back of the heart, supplying the left and back portions of the heart.

Coronary artery disease (CAD) occurs when one or more of the coronary arteries becomes “diseased.”

As we age, “bad” LDL cholesterol is gradually deposited in the wall of the coronary arteries as atherosclerotic plaque. These plaques incite a local inflammatory response, grow over time, can calcify and become rigid, and narrow or even completely block the arteries, like a clogged drain pipe. This narrowing limits the amount of oxygen and nutrients the heart receives. Over time, the vessels may become too narrow to deliver sufficient blood to keep up with the increased demands of the heart when it’s under stress.

Normal Blood Flow

In a heart with normal coronary arteries, the body can regulate the size of the coronary arteries based on the heart’s energy needs. The body can assess how much blood the heart needs and increase or decrease the size of the arteries to deliver more or less blood to match energy requirements.

At rest (low levels of physical activity such as sitting down), the heart doesn’t require much energy. During stress (higher levels of physical activity such as exercising or climbing a flight of stairs), the heart requires more energy, so the body sends a signal to the coronary arteries to expand (dilate) up to ~3-5x larger to allow more blood to be delivered to the heart muscle.

This is a normal physiologic response and is essential to our fight-or-flight response. For example, if you need to run away from a bear, your heart needs to pump faster to deliver more blood to the body (particularly your muscles) so you can run away from the bear. As a muscle itself, the heart also needs more nutrient-enriched blood to sustain more rigorous activity.

The body achieves this by expanding (dilating) the arteries supplying the muscles in use. The heart, therefore, pumps a higher amount (volume) of blood and at a higher rate (your heart beats faster) to significantly increase the amount of blood available to your muscles (whether in your legs or heart) to sustain your run from the bear.

Abnormal Blood Flow

As atherosclerotic plaque builds up, the inside of the blood vessel becomes smaller (more narrow), allowing less blood to pass through and delivering less oxygen and nutrients to the heart.

Diseased blood vessels (generally narrowed by at least 50%) are unable to dilate to accommodate the increased demand and remain narrowed. The heart muscle will still respond to stress by beating faster but will not receive the extra blood needed to sustain the higher activity level.

Nuclear Stress Test - Coronary Artery Disease

The portions of the heart supplied by these diseased arteries may experience a state of inadequate blood flow known as ischemia. Prolonged or severely limited blood flow to the heart can progress from ischemia to infarction, where the heart muscle cells begin to die due to a lack of nutrient-enriched blood.

Heart muscle (myocardium) dying (infarction) is where “myocardial infarction,” better known as a “heart attack,” gets its name. Heart function may be affected when portions of the heart muscle die, depending on the location and amount of heart muscle involved.

When Should You Get a Cardiac Stress Test?

Cardiac stress testing is generally appropriate when a person has symptoms of heart disease that typically worsen with physical activity or exertion. This is especially important when the person has risk factors for CAD, such as family history, high cholesterol, previous heart attack, etc.

Common symptoms of CAD include chest pain, chest pressure (known as angina, sometimes described as feeling like an elephant is sitting on your chest), shortness of breath, dizziness or lightheadedness, and arm discomfort.

If you are experiencing any of these symptoms, please inform your doctor or primary care provider. In medicine, we’d much rather prevent a heart attack than have to treat one.

What is a Cardiac Stress Test?

A cardiac stress test is a medical procedure that assesses the blood flow (nuclear stress test) and function (both echocardiogram and nuclear stress test) of the heart- is there enough blood flow to maintain normal function? The test typically evaluates the heart at rest (low energy requirement) and under stress (higher energy requirement).

The rest portion of the stress test shows the baseline function of the heart. It shows if a heart has any issues at baseline, such as an old heart attack (infarction), limitations of heart function, etc. This baseline allows comparison to see if any problems arise during stress that could be reversed with treatment (restoring blood flow).

Nuclear Stress Test - Stress Cartoon v2

The stress portion of the test is typically achieved by having a patient walk or jog on a treadmill or stationary bike while connected to an electrocardiogram (ECG or EKG) machine to monitor the heart’s response and a blood pressure cuff to monitor blood pressure. Monitoring a patient’s blood pressure and the electrical activity of the heart (via the ECG) screens for signs of heart ischemia (insufficient blood flow) or infarction (heart cell death) during the procedure. The test is immediately stopped and the patient is assessed and treated if there are sings of ischemia or infarction.

There are several types of cardiac stress tests, including an ECG stress test, echocardiogram stress test, and nuclear medicine stress test. An ECG stress test only monitors the heart’s electrical activity. A cardiac stress echocardiogram consists of an ECG stress test with added ultrasound of the heart, directly looking at heart function during stress. These exams look for secondary signs of heart ischemia or infarction: altered electrical activity (ECG) and impaired wall motion (echocardiogram).

Regardless of the type of stress test, all include ECG monitoring to observe the heart’s electrical activity. Patients are monitored for abnormal heart rhythms, particularly life-threatening arrhythmias that would require immediate treatment. Patients are also monitored for signs of a heart attack, such as chest pain or low blood pressure.

For stress echocardiography and nuclear stress tests, imaging of the heart is performed immediately after reaching a sufficient degree of stress.

How is Cardiac Stress Achieved?

Cardiac stress is achieved in one of two ways: via exercise or with the help of medication.

Exercise Stress Test

Exercise stress testing involves physical activity and is the gold standard and preferred form of stress for those who can tolerate exercise.

Nuclear Stress Test - Exercise Stress Test

The type of exercise may vary, with treadmill and exercise bike making up the most commonly used methods. The treadmill or stationary bike settings gradually increase in difficulty level every few minutes until a person is able to reach 85% of their target heart rate (target heart rate = (220 – age) beats per minute (bpm)).

For example, a stress test for a 50-year-old would go up to a heart rate of 144.5 bpm: (220-50)*85% = 144.5 bpm.

Pharmacologic Stress Test

Pharmacologic stress testing uses medicine to simulate stress on the heart. It is reserved for patients who are unable to undergo a regular exercise stress test (e.g., unable to walk, wheelchair or bed bound, etc.) or unable to reach their target heart rate.

A dobutamine stress test is most commonly used for a stress echocardiogram. Dobutamine is a medication that causes the heart to beat harder and faster, causing direct stress on the heart. This increases blood flow to the heart due to the heart “working harder,” just like under regular stress.

A regadenoson stress test is commonly used for a nuclear cardiac stress test. Regadenoson is a medication that acts directly on the coronary arteries and causes them to expand (dilate) by ~3-5 fold, simulating stress. This dilation also increases blood flow to the heart as if it were under stress, but the heart itself has no increased energy demand. A heart with normal arteries will look the same as a heart under stress on nuclear stress images.

Medications are administered via IV and imaging begins once the drug has had sufficient time to take effect.

What is a Nuclear Stress Test?

A nuclear cardiac stress test is a stress test that uses a radioactive substance to directly observe perfusion (blood flow) of the heart. It is used to identify poor blood flow to the heart and look for secondary signs of poor blood flow (ischemia), such as poor heart function, and can help identify blocked arteries.

Aside from injecting a radioactive substance (sometimes referred to as a radioactive tracer or radiotracer), nuclear stress tests use a similar process to the other cardiac stress test variants.

While a stress echocardiogram looks exclusively at heart function, a nuclear cardiac stress test measures blood flow to the heart. A nuclear cardiac stress test is used to diagnose CAD severity and assess for areas of the heart that can be saved – portions of the heart that can survive if perfusion is restored.

A nuclear cardiac stress test can also detect myocardial infarction (dead heart tissue), which is important to distinguish from areas of the heart that can be saved by rapid treatment.

Nuclear Stress Test - Example

This Photo by Unknown Author is licensed under CC BY.

Types of Nuclear Stress Tests

A nuclear cardiac stress test can be performed as a cardiac SPECT (single photon emission tomography) study or a cardiac PET (positron emission tomography) study. These exams are very similar, differing by the type of radioactive tracer injected and the camera used to create the images (SPECT camera vs. PET camera).

Nuclear Stress Test - Gamma Camera

SPECT cameras are more widely available and allow for an exercise stress test to be performed, resulting in a longer medical procedure. PET cameras are typically more expensive and produce slightly better pictures. It is a shorter exam and most PET agents do not leave enough time for an exercise component.

Common radioactive medications used include technetium-99m (Tc-99m) sestamibi and Tc-99m tetrofsomin for SPECT exams and rubidium-82 and nitrogen-13 for PET. Fluorine-18 (F-18) PET radiotracers are in active development and will likely eventually become the dominant PET radiotracer used as F-18 has the best imaging profile.

How is Nuclear Stress Testing Performed?

A nuclear cardiac test, similar to a regular stress test, consists of imaging patients at rest and following exercise or medication-induced stress on the heart.

A radioactive medication is injected via an IV at both rest and peak stress and patients are subsequently imaged on either a SPECT or PET camera.

Images are processed on a separate computer by a physician with advanced training in nuclear medicine. The physician interprets the examination and makes a report available in the patient’s medical record.

Nuclear Stress Test Results

Contrary to its connotation, a negative test result is good! A negative test result means that a person’s heart receives enough blood to keep up with the heart’s increased demands while under stress. Negative is a reassuring result that indicates that there is a low risk of significant CAD.

A positive test result means one or more areas of the heart does not receive sufficient blood to meet the heart’s increased needs while under stress. This could be due to ischemia, which is potentially fixable by intervention (e.g., placement of a heart stent or bypass surgery) or infarction, which is not repairable as the involved heart cells have already died and no longer function.

Nuclear cardiac stress test results can also help determine which artery(ies) is(are) involved based on which portion(s) of the heart is abnormal on imaging.

An indeterminate test result, while uncommon, means the exam is inconclusive. The test was unable to determine if the heart experienced any ischemia (insufficient blood supply) during stress. Indeterminate results may occur in the setting of patient motion during the imaging portion of the exam and sometimes in obese patients on older SPECT cameras lacking CT for attenuation correction (modern SPECT and PET cameras create a rough density map of the patient that is used to remove most of these artifacts).

What are the Radiation Risks?

While radiation may sound scary, rest assured that a nuclear cardiac stress test is safe and commonly used throughout the world. The nuclear stress test was first discovered in the 1960s and has seen (and continues to see) tremendous advances since its inception.

Radiation exposure from a nuclear stress test, while greater than a CT exam, is still relatively low, equal to about 3-4 years’ worth of naturally occurring background radiation (radiation you’re already receiving by living on Earth). This amount of radiation exposure carries a roughly 0.0625% (1 in 1,600) increase in lifetime risk of developing a fatal cancer (assuming an average dose of radiation and an average size person).

Keep in mind that we already have an approximately 20% lifetime risk of developing a fatal cancer. One average nuclear stress test would increase your lifetime risk from 20% to 20.0625%.

When it comes to the heart, the benefit of a nuclear stress test – identifying a heart attack while it’s treatable – far outweighs this minimal risk of future cancer (generally 20 or more years following the radiation exposure). The alternative would be a potentially missed heart attack that could be instantly fatal.


Heart disease, particularly coronary artery disease, is a serious medical condition and the leading cause of death among adults in the United States. This is why signs and symptoms of heart disease, especially chest pain, need to be taken seriously with timely evaluation of the heart to look for a possible heart attack.

Cardiac stress tests play a pivotal role in the evaluation of heart disease. They can be performed as an exercise stress test (preferred) or as a pharmacologic stress test (reserved for people unable to tolerate exercise or undergoing a PET stress test). The type of stress test is typically left to the discretion of the ordering provider and the local availability of each stress test.

A nuclear stress test is one of the most accurate ways to diagnose coronary artery disease, assess for heart tissue damage, and help guide treatment, such as placing stents across the narrowed arteries or, in severe cases, undergoing surgery to bypass the blocked artery(ies).

A nuclear cardiac stress test uses small doses of radioactive material to evaluate perfusion of the heart (how much blood the heart receives) and heart function (how well the pump works). A nuclear stress test can be performed using either a SPECT camera or PET camera.

Patients are exposed to a small amount of radiation from the radioactive tracer injected intravenously for the test. The benefits of the test generally far outweigh any potential risks from the radiation.


Cardiac: Relating to the heart.

Coronary Arteries: Blood vessels that transport blood carrying oxygen and nutrients to the muscles that make up the heart.

Perfusion: Passage of blood from blood vessels into an organ (such as the heart).

Myocardial Perfusion: Blood flowing into the heart.

Myocardial Infarction: Dead heart tissue from blocked blood vessels.

Nuclear Medicine: The use of radioactive substances to diagnose and treat disease processes within the body.

Did you find this article helpful? If so, you may also find these articles discussing incidental findings and the meaning of clinical correlation helpful!