Radiopharmaceuticals and Imaging Techniques

ASSESSMENT OF CARDIAC PERFUSION Thallium-201 Thallium is a potassium analogue that is transported by the Na+,K+-ATPase system in cells, in direct proportion to regional blood flow. Approximately 85 percent of each "pass" of the contrast agent is extracted from the blood across the capillary bed. Thallium is initially extracted by myocardial cells but then redistributes to maintain an equilibrium with the blood at a rate that is proportional to regional blood flow. Thus, the early images from a thallium scan reflect blood flow, and the later images (redistribution phase) reflect the intracellular K + blood pool. The intracellular K + blood pool in turn is reflective of cellular viability. The redistribution phase is usually imaged at from 4 to 24 h after the initial injection of thallium.

In combination with exercise or pharmacologically induced coronary hyperemia (from dipyridamole or adenosine), thallium imaging is able to distinguish normal blood flow, ischemia, infarction, and hibernating myocardium. Myocardial tissues distal to a physiologic coronary artery stenosis are unable to increase their blood supply during stress conditions or hyperemia and thus have low radiotracer activity. on 4-h-delayed images, however, the thallium redistributes to these arrows and the radiotracer activity of the myocardium becomes more uniform. With infarction, delayed images show no evidence of radiotracer redistribution, reflecting the lack of intracellular K+ blood in the area of infarction. With hibernating myocardium, redistribution occurs by 24 h.

Technetium Technetium radionuclides offer greater ease of use and availability for nuclear medicine departments. Whereas thallium requires a cyclotron to produce, technetium agents are widely available and produced by a generator in each nuclear medicine laboratory. The most commonly used technetium agent is technetium-99m sestamibi (99mTc-sestamibi). This agent is taken up by the myocardium in direct proportion to myocardial blood flow. At this point, the sestamibi molecule becomes trapped within the myocardium and does not redistribute (contrary to the behavior of thallium). Thus, the initial uptake by the myocardium reflects blood flow at the time of injection. Typically, 99mTc-sestamibi is initially injected at peak exercise, or during the period of maximum coronary vasodilatation (induced by dipyridamole or adenosine).

Since 99mTc-sestamibi does not redistribute on delayed images, myocardial infarction and decreased flow from physiologically significant coronary stenosis both appear as myocardial defects on images. To differentiate these two possibilities, a second dose of 99mTc-sestamibi is given while the patient is at rest. If the rest images show uniform radiotracer distribution, then the defect seen on stress images is due to ischemia. Persistent areas of absent radiotracer on rest images indicate areas of myocardial infarction.

GATED RADIoNUCLIDE ANGIoGRAPHY Gated radionuclide angiography (RNA) has remained a clinical gold standard for overall assessment of left ventricular function. This test has the advantage of being applicable to nearly all patients, regardless of body habitus or underlying illness. In addition, unlike echocardiography, RNA is relatively operator independent. Radiation exposure is present but insufficient to prevent serial examination of cardiac function in the same patient.

In RNA, a blood sample is labeled with a technetium-based radionuclide, and a series of images of the heart is acquired. These images are gated to the R wave of the electrocardiogram. Function, and measurement of ejection fraction, involve measuring radioactivity counts at multiple time points throughout the cardiac cycle. The number of radioactive counts is directly proportional to the blood volume in the cardiac chamber. Thus, the method is insensitive to the precise geometry of the left ventricle, since only the overall count rates, and thus volumes, are measured. other than segmentation of the left ventricle from other cardiac cavities, no geometric assumptions regarding left ventricular anatomy are necessary with the technique. Using gated techniques, with display of images as a cine loop, it is possible to assess segmental function of the heart. However, the resolution of the images is limited, and the strength of the examination relies primarily in accurate quantitation of the global left ventricular function.

Ventricular function is assessed by qualitative evaluation of cardiac wall motion, and quantitative assessment of radionuclide counts as a function of time. Computer-generated curves are verified by an experienced observer's interpretation of regional wall motion determined by gated RNA studies. RNA allows particularly good views of the lateral wall of the left ventricle, where there is no overlap from other cardiac segments. Although systolic function is easily assessed, diastolic function of the left ventricle is more commonly performed by echocardiography.

FIRST-PASS CARDIAC STUDIES If the radionuclide is rapidly injected, and the acquisition speed of the nuclear images is rapid, the "first pass" of the radionuclide can be tracked, as it passes through the heart. This method relies on tracking of the radionuclide bolus as it passes through the ventricular cavities immediately following contrast injection. In this technique, the acquisition time is very rapid (30 s), although very few heartbeats are evaluated, thus limiting spatial resolution.

Left ventricular ejection fraction measurement is determined by following the passage of the radiotracer between the left and right ventricles. The injection of the radiotracer must be rapid, or poor separation of radiotracer between the two sides of the heart occurs. Patients with dysrhythmias, atrial septal defect, or significant regurgitation across the mitral or tricuspid valves will have poor ejection fraction estimates using this method. First-pass studies using 99mTc-sestamibi enable cardiac function as well as perfusion to be assessed in the same study.

GATED PERFUSIoN IMAGING Following injection of 99mTc-sestamibi, images can be collected such that multiple time points, or cine frames, during the cardiac cycle can be independently collected by gating data acquisition to the cardiac cycle. In this manner, a cine loop, or movie of the cardiac cycle, can be generated. The function of the heart can be qualitatively reviewed to assess for wall thickening or segmental dysfunction. Thus, the perfusion of the heart can be assessed in the same setting as cardiac function. Functional imaging aids in discriminating between true mild perfusion defects and imaging artifact, such as due to attenuation from overlying breast tissue or the diaphragm. When severe perfusion defects are present, due to infarct or significant coronary artery narrowing, accurate estimation of ejection fraction is difficult to measure.

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