Nuclear Medicine in the Diagnosis of Heart Disease
Kevin P. Tracey
MD, FRCPC, ABNM
Medical Director- Nuclear Medicine
Hotel-Dieu Grace Hospital
Nuclear Medicine in the Diagnosis of Heart Disease
Nuclear Medicine plays a vital role in the diagnosis of the patient with heart disease on a daily basis in hospitals and clinics across this country. In addition to aiding diagnosis, it frequently guides or directs therapy as well as monitors the success of those therapies in cardiac patients. We will look at its role in routine clinical practice and how it is best utilized given some common clinical settings.
Let’s familiarize ourselves with the most common techniques used in Cardiac Nuclear Medicine today.
Myocardial Perfusion Imaging
By far, the most frequent tool used in Cardiac Nuclear Medicine departments is the Myocardial Perfusion Imaging study (MPI). This technique was previously more commonly referred to as a stress Thallium study. It has been re-named because the radiotracer used previously, Thallium-201, has been replaced for the most part by Technetium-99m-MIBI (MethoxyIsoButylIsonitrile) or Tc99m-Myoview (Tetrofosmin). These latter two agents allow better images of the heart using the current Single Photon Emission Computed Tomography or SPECT cameras in use today.
MPI involves injecting these tracers intravenously which localize within the heart muscle in direct relation to a patient’s cardiac blood supply. The tracer distribution reflects this blood supply at the time of injection providing a « snapshot » of what has occurred up to three hours earlier when imaged under the camera later. Thus, a patient who is stressed on a treadmill or who is injected while having a spontaneous episode of chest pain can be imaged later when stable and the images can be compared to a study done while the patient is at rest or pain-free.
Also, in addition to looking at heart perfusion, we can look at wall motion and wall thickening with these agents using a technique called « gated SPECT. » From this, we can estimate the heart’s Ejection Fraction or EF, which is a valuable measurement tool of the heart’s pumping ability.
Stress MPI is performed in two steps. The first step involves an injection of Tc99m-MIBI or Myoview at rest. Imaging under the camera is typically performed an hour later. Later the same day or on a separate day, the patient is exercised on a treadmill or, in patients unable to walk on a treadmill, given a drug that gives the same information as exercise.
Dipyridamole (or in the USA Adenosine) is used as the stressing drug in most patients who cannot adequately exercise, but also in patients who have a Left Bundle Branch block on ECG or patients who cannot or have not stopped their beta-blocker medication. It is contraindicated in uncontrolled asthmatics. Dobutamine is an alternative stressing drug for those patients.
At peak stress they are injected with the Tc99m-MIBI or Myoview and imaging repeated. The computer generated images of the blood supply to the heart are compared, slice by slice (Figure 1). These are inspected visually by the nuclear medicine physician, but are also compared to a sex-matched normal database. Perfusion defects present at rest generally indicate previous myocardial infarction (although artifacts and chronically ischemic tissue can also appear this way) (Figure2).
Reversible defects, that is, defects occurring during the exercise or stress study only, which show normal blood supply at rest, represent ischemic areas of heart tissue which are at risk for a myocardial infarction or heart attack (Figure 3).
The investigation of patients at risk for ischemic heart disease requires assessing the pre-test likelihood of disease in a particular patient. This is because MPI is best used for patients at an intermediate risk of having the disease.
MPI is generally a second tier study done in patients who have undergone a previous treadmill study in whom a diagnosis of ischemic heart disease cannot be made or in whom the volume of at risk myocardium needs to be determined. It is, however, also of great use in patients with resting ECG changes in whom a standard treadmill study will be non-diagnostic. As mentioned, pharmacologic stress MPI studies are a first tier study in patients who are unable to exercise, in patients unable to achieve a heart rate of 85% of their age-predicted maximum heart rate, but also in LBBB patients, because of a specific false-positive finding that occurs when these patients undergo a treadmill MPI.
Also, Persantine (or dipyridamole) MPI is particularly useful in the early days following a heart attack, when it can be safely used to study a patient as an alternative to exercise.
Increasingly, Stress MPI nuclear studies are being used as an initial investigation in women at intermediate risk for heart disease and diabetic patients, as we recognize the difficulty in diagnosing cardiac disease in these patients. Often, heart disease is silent and the standard treadmill study alone misses disease in these and other higher risk patient populations.
Stress MPI is used to direct which vessel is the likely « culprit » vessel in patients with two or more known diseased coronary arteries. Furthermore, once a patient has been treated either with bypass surgery, angioplasty or stent or with medical therapy, MPI is used to monitor response to therapy.
Pre-operative risk assessment of patients at risk for a cardiac « event » during or following surgery, particularly vascular surgery, is another common and vital role for this technique. The categorization of patients into low versus intermediate versus high risk frequently allows for identifying and treating a patient’s heart disease before they have what may otherwise be a fatal surgical complication.
In some centers, injection of patients who present to the ER with chest pain with MIBI or Myoview can be a valuable tool when the ECG and enzyme markers are non-diagnostic. The presence of a normal examination can allow for early discharge and a low-risk categorization.
By far the most common use of this technique is in chest pain assessment. More and more in this country the MPI allows appropriate risk stratification and serves frequently as a gate-keeper to diagnostic cardiac catheterization. This non-invasive tool allows the most strategic and cost-effective use of this more limited resource.
Utilizing the technology of CT scanning, combined with Nuclear Medicine SPECT gamma cameras, SPECT-CT systems are now in place in most major centers. Using a low-dose CT of the heart done in conjunction with the gated SPECT MPI study reduces the number of artifacts in women and obese patients secondary to breast tissue and soft tissue « attenuation » artifacts respectively. The normal loss of information in these patient’s studies is corrected by data from the CT study. The radiation dose received by the patient from these studies is low and still well within the diagnostic range.
Ancillary information such as coronary artery calcification and even unsuspected lung and breast cancers have frequently been incidental discoveries during these procedures.
Multi-Gated Cardiac Study or MUGA
The Multi-Gated cardiac study or MUGA is the other most common tool used daily in Nuclear Medicine departments. It is sometimes referred to as an Equilibrium RadioNuclide Angiogram (ERNA or RNA) or Gated Blood Pool Study. This study involves labelling a small sample of the patient’s red blood cells with the radioisotope Technetium (Tc99m) and then re-injecting them intravenously. The labelled red cells remain for the most part in the blood pool and dynamic images of the heart are obtainable.
The « gating » relates to the recording of the data relative to a particular segment of the cardiac cycle when timed to the patients ECG complexes. A composite moving image of the heart is built up over a period of anywhere from two to ten minutes. The images can be acquired with the SPECT technique as well, resulting in both 2D and 3D images. They are then visually assessed for wall motion abnormalities. While typically done as a resting study, Stress MUGA examinations can also be performed.
Echocardiography is used more commonly to assess the heart non-invasively because of its ability to assess both wall motion and structure as well as valve assessment without exposing the patient to radiation. The MUGA study is still important today, however, for its ability to more accurately quantitate the Left Ventricular Ejection Fraction (LVEF), an important measure of cardiac function.
MUGA studies utilize a more accurate and reproducible « count based » method for determination of the LVEF rather than a geometric formula. Its value as a monitoring tool such as in patients at risk for chemotherapy-induced cardiotoxicity or for optimal selection of patients for techniques such as Implantable Cardiac Defibrillators makes it still in wide use today.
Stress MUGA studies are also still performed by labs utilizing the response of a patient’s LVEF while exercising as a tool to help decide on the timing of valve replacement.
First pass cardiac techniques can be used in conjunction with the MUGA study to assess for intracardiac shunts and to obtain quantitative information about the Right Ventricle. This technique of obtaining very rapid images and radioactivity counts as the injected tracer passes through the heart on its first pass isolates the different chambers and allows for RVEF determination as well.
Myocardial Viability Studies
In patients where large rest defects are seen on a MPI study and heart failure is present, the possibility exists that the defects represent areas of chronically ischemic and hibernating myocardium, rather than dead or infarcted tissue. This is important because by bypassing these patients, they can regain cardiac function. PET or Positron Emission Tomography is the most accurate tool for assessing for hibernating myocardium. Its availability remains limited, however, and in many centers Thallium-201 viability imaging can make the diagnosis albeit with reduced sensitivity.
Patients are injected at rest and a SPECT cardiac study is performed after 30 minutes. A repeat study is then performed at four hours after the initial injection. The studies are combined and computer analyzed. Areas of thallium redistribution represent viable but hibernating myocardium. A negative study does not exclude potentially salvageable tissue, however, and the patient may still benefit from PET imaging.
Summary and Future Directions
We have discussed the most common Cardiac Nuclear Medicine procedures used in clinical practice today. Less frequently utilized studies such as imaging of Cardiac Denervation using MIBG (MetaIodoBenzylGuanidine), imaging of Apoptosis, Atherosclerotic imaging and other exciting and evolving Molecular Imaging techniques promise a « new and clear » future for Cardiac Nuclear Medicine.
