Fundamentals of Diagnostic Radiology
3rd Edition

Chapter 57
Cardiovascular System Scintigraphy
David K. Shelton
Michael F. Hartshorne
Nuclear medicine applications in the cardiovascular system include gated or nongated myocardial perfusion imaging, myocardial viability studies, infarction imaging, gated ventricular function studies of the blood pool in the ventricles, and detection and quantitation of intracardiac shunts.
Each of the perfusion agents may be imaged with planar techniques or with SPECT. Meticulous quality control of the stress and rest images is essential. The comparison of images between stress and rest requires identical repositioning so that the same areas of myocardium are visualized. Poor positioning will lead to false-positive interpretations of ischemia and infarct.
The three principle coronary artery distributions of the LV are the left anterior descending artery (LAD), the left circumflex artery (LCX), and the posterior descending artery (PDA). Each artery normally provides an equal intensity of myocardial labeling at any given level of cardiac work. Perfusion of the thinner right ventricular wall is considerably less than that of the LV, but it can be imaged using the same techniques (Figs. 57.1, 57.2, 57.3).
Exercise on a treadmill, or simulation of exercise by infusion of dipyridamole or adenosine, is used in conjunction with perfusion agents to increase radionuclide delivery to the normal myocardium. Stepwise increases in physical exercise are monitored by sequential electrocardiogram (ECG) and blood pressure and pulse measurements while the patient is queried for symptoms of angina. The radiopharmaceutical is injected under conditions of maximal exercise, which should be continued for 30 to 60 seconds after injection to obtain optimal mapping of stress perfusion. Exercise should reach at least 85% of the maximum predicted heart rate to achieve adequate stress. Exercise may also be stopped because of chest pain and ischemic changes on the ECG. Adequacy of the exercise challenge can be more thoroughly estimated simply from a calculation of the “double product” (DP) (systolic pressure × heart rate = DP). The DP correlates with an individual’s myocardial work performed, whereas the duration of exercise and heart rate alone may not. For exercise to be judged as adequate, the DP should double, or preferably triple, from rest to peak exercise and should rise to above 20,000.
For those patients who cannot perform physical exercise, coronary vasodilatation can be pharmacologically induced. IV dipyridamole or adenosine will vasodilate normal coronary arteries but does not effectively increase flow through vessels with 50% stenosis or greater. Those areas, which cannot dilate normally, will appear to have decreased myocardial perfusion when compared with the rest of the myocardium.
IV dobutamine can also be used when dipyridamole or adenosine are contraindicated, such as active bronchospasm. Dobutamine has direct inotropic and chronotropic effects that result in increased coronary flow

similar to true exercise. Areas of relative hypoperfusion result from coronary stenosis.
FIGURE 57.1. Normal Exercise/Rest Planar Technetium-99m Sestamibi Myocardial Scan. Anterior (ANT), left anterior oblique (LAO 40, LAO 70), and left lateral (L LAT) planar views of a 380-pound patient, with the upper row representing stress and the lower row representing rest injections of the radiopharmaceutical. Note the superb image quality in spite of the patient’s large size.
Image Acquisition
Planar imaging has largely been replaced by SPECT imaging with reconstruction of the LV myocardium into short-axis, vertical long-axis, and horizontal long-axis planes. A 180° acquisition is generally preferred over 360° acquisition because of the asymmetry of the heart in the thorax and owing to spine attenuation effects in the posterior projections. ECG gated acquisitions are readily accomplished for technetium and thallium radiotracers, allowing evaluation of wall motion, brightening, and thickening from diastole to systole. Functional data acquisition has also become routine, allowing accurate calculations of end-diastolic volume, end-systolic volume, and left ventricular ejection fraction (LVEF). ECG gated planar imaging can still be accomplished for patients who cannot be imaged on the SPECT table (often because of weight).
FIGURE 57.2. Normal SPECT Projections. Short-axis (A), vertical long-axis (B), and horizontal long-axis (C) images in standard projections show the walls of the LV. In the short-axis images, an apical “button” starts the series, which extends back to the base of the ventricle. The names of the walls for the short-axis images are best given by the diagram in Fig. 57.3. In the vertical long-axis images, the anterior and inferior (or posterior) walls are seen. In the horizontal long-axis images, the short septum and long lateral or “free” walls are well seen. The long-axis images also show the apex very well.
The tomographic images from SPECT have improved the accuracy of myocardial perfusion imaging (MPI) and provide better correlation to other imaging modalities such as echocardiography, CT, and MR. The addition of ECG gated SPECT allows wall motion analysis and functional information, which has improved interpretation and made MPI a more complete examination.
Prone imaging is frequently accomplished after the standard supine, post–stress acquisition, and may help reduce false-positive results caused by breast or diaphragm attenuation, hot bowel loops, or motion artifacts. Attenuation correction can also be accomplished with emission

sources or on the new SPECT-CT devices. The SPECT camera itself can be a single-, dual-, or triple-headed camera.
FIGURE 57.3. LV Short Axis Vascular Distributions and Wall Names. The schematic diagram locates the expected position of the principle coronary arteries. The left anterior descending artery (LAD) usually serves the apex. The names of the wall segments are listed in a clockwise fashion as anterior, anterior-lateral, lateral, inferior-lateral, inferior, inferior-septal, septal, and anterior-septal. The LAD sends diagonal vessels (numbered with digits in the order in which they leave the LAD, e.g., D1, D2, etc.) onto the anterior and anterior-lateral walls and septal perforators down into the septum. The left circumflex (LCX) sends obtuse marginal (OM) branches along the free wall, numbered in sequence (OM1, OM2, etc.) The posterior descending artery (PDA) arises from the right coronary artery (RCA) 85% of the time and serves the inferior wall and the inferior-septal wall.
Three gamma-emitting radiopharmaceuticals are readily available for mapping the flow of blood to the myocardium. Each has advantages and some disadvantages.
Thallium-201 (Tl-201), an analog of the potassium ion (K+), is delivered to capillary beds by regional blood flow and is actively pumped into viable cells by the sodium/potassium (Na+/K+) adenosine triphosphatase pump. Cyclotron production at a remote site (requiring shipping); a long physical half-life (73 hours); low-energy, poorly penetrating photons (mostly 69- to 83-keV γ rays); and a relatively high absorbed dose (0.24 rad/mCi for the whole body at the usual dose of 2 to 5 mCi) combine to make Tl-201 a less-than-ideal agent for imaging. However, because of its active transport into cells, it is a more physiologic radionuclide than the technetium-99m (Tc-99m)–labeled agents.
A widely used technique utilizes Tl-201 with exercise stress or a pharmacologic challenge. Images are usually acquired as soon after injection as possible. However, some authors advocate waiting for 5 to 10 minutes to allow the exercised patient to stop breathing heavily so that movement of the heart heaving up and down with the diaphragm will be minimized. This slight delay also limits an artifact caused by the “upward creep” of the heart. As the lungs decrease in volume slowly after exercise, the average level of the diaphragm is raised, shifting the heart upward. This shift in location of the heart produces an artifactual shift in radionuclide activity that may be misinterpreted as ischemia.
The effective half-life, or 50% washout, of Tl-201 from the normal myocardium is about 4 hours. A complex “redistribution” of the isotope within the myocardium is governed by rates of washout from myocardial cells, renal

excretion, and shifts of the isotope between muscle, viscera, and other compartments. Rest or redistribution imaging is usually done 3 to 4 hours after the stress injection. Because Tl-201 has significant blood pool activity, it can slowly redistribute into the myocardium and thus slowly fill in ischemic-type defects. In addition to clinical data (ECG, angina, etc.), the initial Tl-201 images of the chest and heart may help assess the heart’s performance. High lung activity immediately after exercise usually indicates that left ventricular failure occurred during exercise. Poststress dilation of the heart compared to the resting images is another indicator of failure. Both phenomena have a severe prognosis for subsequent cardiac events (angina, infarction, arrhythmia, and sudden death) (Fig. 57.4). Another imaging strategy for improving the visual detection of ischemic myocardium by Tl-201 scintigraphy calls for a “reinjection” of 1 mCi of Tl-201 just before delayed rest imaging. This technique is especially important to view defects caused by very high-grade stenoses, resulting in more accurate diagnosis of ischemia versus infarction.
FIGURE 57.4. Abnormal Thallium-201 Lung/Heart Ratio. This frame is an anterior projection acquired immediately after the start of a stress SPECT study. The lung:heart ratio of 0.77 is markedly elevated, indicating that the patient experienced heart failure during exercise.
Tc-99m is used to label two commercially available myocardial perfusion agents.
Tc-99m Sestamibi (trade name Cardiolite) is taken up by the perfused myocardium by passive diffusion and is bound in the myocyte, mostly within myocardial mitochondria. There is no significant redistribution effect with this agent. Washout is negligible. Imaging of the 15- to 20-mCi dose is delayed for 30 minutes to 1 hour after stress to allow for biliary and background clearance. Because there is neither redistribution nor significant washout of Tc-99m sestamibi, a repeat injection of 15 to 20 mCi for resting images is commonly performed on a different day. With this 2-day protocol, stress imaging is usually done first. An alternative 1-day approach uses a small dose (8 mCi) for the initial rest scan, followed 4 hours later by the stress scan, with a larger dose of 20 to 25 mCi.
Tc-99m Tetrofosmin (trade name Myoview) is rapidly extracted from the blood by perfused myocardium in a fashion that resembles Tc-99m sestamibi. The manufacturer claims that it clears background faster and therefore can be imaged sooner than Tc-99m sestamibi. The two agents have proven to act clinically in a very similar manner, but availability and pricing make important considerations.
Both of the Tc-99m–labeled agents are prepared from Tc-99m pertechnetate and stocked pharmaceutical kits. Both are easy-to-image radiopharmaceuticals with good soft tissue penetration (140 keV gamma energy) and a high photon flux from typical doses of 8 to 25 mCi. In addition, the Tc-99m agents also provide perceptibly improved image quality and an opportunity with the same injection to better perform gated first-pass or gated SPECT studies, which can be used to evaluate wall motion, and left ventricular functional parameters such as LVEF.
Dual-Isotope Myocardial Scans
An innovative way to maximize the logistical patient throughput involves the use of a Tl-201 and a Tc-99m agent for sequential scans. The most widely used dual-isotope scan technique uses a resting Tl-201 scan, which can be immediately or subsequently followed by a Tc-99m (sestamibi or tetrofosmin) stress scan. Because the energy and photon flux of the subsequent Tc-99m scan are higher than those of the Tl-201 scan there is no problem with cross talk between the rest and stress images. Excellent scan quality can be combined with 1-day convenience, or a delayed 24-hour thallium scan can be accomplished if needed.
Myocardial Ischemia
Interpretation of myocardial perfusion scans is difficult but important. Subtle abnormalities can signal serious coronary artery disease. Observer knowledge and experience are essential for an accurate diagnosis. Parametric methods of perfusion image analysis have been employed in attempts to standardize diagnosis. Circumferential profiles of isotope distribution and analyses of regional rates of Tl-201 washout, compared with normal databases, make interpretation more sensitive in the detection of ischemia. Displayed as graphic data, “bull’s-eye” maps of SPECT images, and three-dimensional reconstruction of SPECT data, these aids in interpretation may be overly sensitive. If an abnormality is truly present, it should also be visible in the planar or SPECT images. Depending on the statistical assumptions used and the population studied, the sensitivity and specificity for detecting

myocardial ischemia are in the percent range of the high 80s or low 90s. It is important to remember that according to Bayes theorem, the positive and negative predictive values of a test will vary according to the prevalence of disease in the population being tested. The myocardial perfusion scan also detects other causes of ischemia (including left bundle branch block, coronary vasculitis, and small vessel disease) that cannot be seen on coronary arteriography and thereby reduces its apparent specificity. In addition to detecting significant coronary artery disease, the presence and severity of ischemic myocardium correlates strongly with the prognosis for adverse cardiac events, including angina and cardiac death (Fig. 57.5).
Myocardial perfusion imaging demonstrates relative regional perfusion. Areas of myocardium with poor blood supply, usually because of atherosclerosis, fail to increase radiotracer uptake during the stress component. The most important feature of the myocardial perfusion test is comparison of the stress and rest images to detect areas of ischemia that are inadequately perfused at exercise yet still viable. These areas are redundantly called reversibly ischemic. Ischemia detected by exercise or pharmacologic dilation of normal vessels usually corresponds with angiographic abnormalities in coronary arteries. Correction of the anatomic abnormality by angioplasty, laser atherectomy, or coronary artery bypass surgery is expected to relieve the ischemia. A frequent location of ischemic tissue is immediately adjacent to an area of infarct. This is called peri-infarct ischemia and does not portend the same clinical significance as an ischemic or reversible zone.
Some patients will have naturally recruited coronary collaterals or bypass grafts that produce apparent discrepancies between angiographic and scintigraphic studies. Abnormal anatomy in a coronary artery may not produce hemodynamically significant changes in blood flow to the myocardium, and not all ischemia is produced by large vessel atherosclerosis. Capillary disease in diabetics, left bundle branch block, vasospasm, vasculitis, or cardiomyopathy (dilated or hypertrophic) may produce ischemic myocardium even with normal arteries. Ischemia may not

be detected if there is inadequate exercise, inadequate pharmacologic challenge, or balanced triple-vessel disease. Fortunately, it is uncommon for all three coronary arteries to be hemodynamically compromised equally, and poststress dilation will usually be present.
FIGURE 57.5. SPECT of Left Anterior Descending Artery Reversible Ischemia. The row of short-axis stress images (A) has a perfusion defect in the anterior wall, which perfuses normally in the rest of the short-axis images (B). This is also visible in the horizontal long-axis stress (C) and vertical long-axis stress images (E), which have the same perfusion defect. At rest the matched images (D, E, F) show normal perfusion.
FIGURE 57.6. Hibernating Myocardium. Two vertical long-axis thallium-201 images at rest (A) are compared with matched images at 24 hours (B). The large anteroapical defect (arrows) partly fills in over time, indicating that some hibernating (viable) myocardium is present in the midst of what looked initially to be infarcted tissue.
Hibernating Myocardium
Severe ischemia with high-grade stenosis may be so slow to “reverse” on Tl-201 imaging that it will not be detected by rest or redistribution images at 3 to 4 hours after stress. Imaging at 24 hours, or a Tl-201 second injection rest study, may be required to detect extreme ischemia. The Tc-99m–labeled agents are routinely given as two separate injections, but evidence suggests that rest-injected Tl-201 with delayed imaging may be best for detecting the severe ischemia that leads to a phenomenon known as hibernating myocardium. Hibernating myocardium is important to diagnose, as it simulates infarction by not contracting at rest. It remains viable, however, and will return to normal function after revascularization (Fig. 57.6).
Myocardial infarction produces layers of nonperfused scar tissue that are detected as areas of thin myocardium with decreased radiotracer uptake at both stress and rest imaging. The extent of an infarct, from subendocardial to transmural, is reflected by the size and degree of the perfusion defect (Fig. 57.7). Technical artifacts from attenuation of the perfusion agent’s radiation may be produced by SPECT tables, breast tissue, and subdiaphragmatic structures. These may appear as fixed defects superimposed on planar or SPECT images, which may lead to a false-positive reading of infarction. A false-positive interpretation of ischemia should not occur as long as the artifact does not change between stress and rest imaging.
Three techniques are in use to reduce the artifactual appearance of fixed defects seen with myocardial perfusion scanning. The simplest relies on repeat poststress scanning of the patient in the prone position with a Tc agent. This changes the position of the heart, breasts, diaphragm, and subdiaphragmatic organs and reduces the appearance of fixed defects in the appropriate distribution, which may be misinterpreted as infarctions. Repeat prone positioning scans may also help with motion artifacts. Unfortunately, obese patients in whom there is plenty of breast or subdiaphragmatic attenuation may not be able to lie prone for this scan (Fig. 57.8).
Another technique that avoids misinterpretation of fixed artifactual defects as infarctions relies on gating the acquisition. It is a very simple technique with planar scans and somewhat more involved with SPECT scans. A cine replay of the gated study allows assessment of wall motion. The normal wall moves inward during systole, thickens as it contracts, and becomes brighter on the display. An area in question that demonstrates normal wall motion, brightening, and thickening is probably not infarcted.
The elegant solution to the problem of attenuation artifacts has only recently become available. This attenuation correction relies on the simultaneous SPECT acquisition of an emission scan and a transmission scan performed with a radioactive source of a different energy than that used for the emission scan. The transmission scan can also be acquired with the CT component of SPECT-CT. With a transmission scan, allowance for the emission

photons lost because of attenuation can be made, and the resulting SPECT scans are surprisingly free of artifacts. A related improvement on this scheme incorporates correction for photons scattered from the emission source but still accepted by the imaging system. A combination of attenuation and scatter correction promises truly quantitative imaging in the future (Fig. 57.9).
FIGURE 57.7. Resting Images of Infarcts of the Left Anterior Descending Artery (LAD). Short-axis (1A) and horizontal long-axis (1B) SPECT images show a small anterior LAD infarct (arrows). This is compared with another patient who has a much larger LAD infarct (2A, 2B) in the same vascular distribution (arrows). Note that the second patient’s infarct extends from the anterolateral wall to and including the septum. The ventricle is also dilated at rest.
Stunned Myocardium
A single myocardial perfusion scan cannot determine the age of an infarct. Acute infarcts usually appear larger than old infarcts when imaged with Tl-201. Temporarily damaged cells around infarcted cells, referred to as “stunned myocardium,” will be hypokinetic or akinetic and will not hold on to the Tl-201 until recovery several weeks later. Thus the defect can appear worse on the rest imaging compared to the stress imaging, in a so-called “reverse redistribution.” The abnormality may revert to normal or shrink as repair occurs.
Infarct-Avid Scans
Acute infarcts may also be detected with Tc-99m pyrophosphate labeling. Ionized calcium released from myocytes forms dystrophic calcifications with phosphates, and a “hot spot” is formed, marking the infarcted tissue. Antimyosin antibodies labeled with Tc-99m or indium-111 also localize on the fringes of acute infarctions. The need for imaging of acute infarction is clinically infrequent, usually when the patient has left bundle branch block. Contused myocardium is also detected with these techniques.
Positron Emission Tomography
PET is more expensive than standard myocardial perfusion imaging but offers the advantages of coincidence imaging, higher-energy photons, efficient attenuation correction, and different radiopharmaceuticals. PET agents can also be imaged on hybrid SPECT cameras or SPECT cameras with heavy collimators. PET scanning with coincidence detection allows high photon flux because collimators are not required. PET scans have higher-resolution images and fewer attenuation artifacts than standard MPI. Thus, PET scans may be the gold standard for MPI.
For PET scans, stress testing is usually done with pharmacological agents. Perfusion is usually evaluated with rubidium-82 or ammonia-13


(13NH3), with comparisons of rest imaging with stress imaging, as in standard MPI. Viability or hibernating myocardium is evaluated with resting injection of fluorine-18 fluorodeoxyglucose (FDG).
FIGURE 57.8. Stress Versus Prone Imaging. Technetium-99m sestamibi imaging with a single headed SPECT camera shows a defect in the inferior wall during stress imaging (arrowheads), which is not present when the patient is imaged again in the prone position.
FIGURE 57.9. Attenuation Correction. An apparent anterior wall defect caused by large breasts is corrected by simultaneous transmission and emission scans. An uncorrected vertical long-axis scan (A) shows an apparent anterior wall defect, which disappears when the transmission scan (B) is used to correct for the asymmetric attenuation (C). The anterior wall (arrows) is normal.
FIGURE 57.10. Fluorodeoxyglucose (FDG) PET Myocardial Viability Scan. Tc-tetrofosmin resting scan (A) shows defects in the anterior and inferior walls on male for potential bypass surgery. Fluorine-18 FDG resting PET scan (B) demonstrates normal uptake consistent with fully viable, hibernating myocardium.
In evaluation of coronary artery disease, rubidium or ammonia-13 pharmacologic stress imaging is accomplished, and defects, which reverse on rest imaging, are indicative of coronary stenosis. Fixed defects on stress and rest usually identify infarcted myocardium or hibernating myocardium. With FDG imaging, hibernating myocardium will show normal or even relatively increased FDG uptake as the result of a shift from free fatty acid metabolism to glucose metabolism (Fig. 57.10). True infarction will show no significant FDG uptake.
The radionuclide ventriculogram (RVG) is a study that uses circulating, Tc-99m–labeled red blood cells to evaluate the size, wall motion, and functional parameters of the LV. RV evaluation is better accomplished by the first-pass study, to be discussed later.
The red blood cells are labeled with Tc-99m, utilizing one of several techniques, and make an excellent blood pool imaging agent. Doses of 20 to 30 mCi are commonly used for typical adult patients. ECG leads are placed to obtain a suitable gating signal (the R wave) for the computer. With the ECG as a measure of the cardiac cycle length, the cardiac cycle is divided into a minimum of 16 frames for analysis of systolic function. Higher temporal resolution of 32 frames per cardiac cycle is required for good measurement of diastolic function. The result of this acquisition is a composite, “averaged” series of images representing the patient’s cardiac cycle. Data from a sufficient number of cardiac cycles (several hundred) must be obtained to make the images statistically significant for analysis. Typical acquisition time is 5 to 20 minutes per view (Fig. 57.11).
Analysis of the functional parameters of the LV, including the LVEF and first derivative (dV/DT; where V is LV volume and T is time) of the LV volume curve, is most accurate from images obtained in the “best septal” left anterior oblique view. This view produces the greatest separation of the activity of the LV from that of the RV.
FIGURE 57.11. Normal Gated Blood Pool Image. An end-diastolic image is shown with a computer-generated region of interest around the LV blood pool. The RV is adjacent.
FIGURE 57.12. Left Ventricular Time Activity Curve. The graph shows this curve (from the patient in Fig. 57.11) that displays the ventricle’s relative volume during the cardiac cycle. The vertical dashed line represents the relative stroke volume, expressed as an ejection fraction of 62%. The curve begins at end diastole, A marks end systole, B marks the start of diastolic filling, C marks the peak filling rate, D is the end of rapid filling, and E represents the beginning of the atrial “kick.” The horizontal dashed line shows the interval of the first third of diastole, during which more than half of the stroke volume is recovered.

Computer processing of the image data by spatial and temporal smoothing algorithms improves both the visual analysis of wall motion and the accuracy and precision of the derived functional parameters. Outlining the edge of the ventricular blood pool in each frame of the study with computerized second-derivative edge detection methods is superior to threshold detection or manually drawn regions of interest. The volume curve is generated by plotting the number of counts in the ventricle versus time during the cardiac cycle. This curve generates the LVEF, which measures the change in volume between end diastole and end systole. The LVEF is the single best parameter of LV function (Fig. 57.12).
Arrhythmias such as frequent premature beats and atrial fibrillation tend to falsely lower the LVEF. The R-R (R-wave) interval histogram from the ECG can demonstrate the presence of arrhythmias. Most nuclear medicine computer systems allow analysis of selected populations of beats of the same R-R interval to yield a more accurate LVEF.
Additional functional parameters are easily obtained. The dV/DT of the LV volume curve gives important information on the rates (average or maximal) of systolic emptying and diastolic filling.
Cardiac output (CO) in liters per minute may be calculated if the heart rate, the LVEF, and the left ventricular end-diastolic volume (LVEDV) are known. The product of all three is CO. The LVEDV can be measured by comparing the count rate of a blood sample of known volume with the count rate of the ventricle at end diastole and end systole.
Another simpler method to measure CO uses a count-based ratio method. The ratio of the total counts to the maximum counts in the diastolic frame is entered into an equation that also requires a calibration of the voxel size for the acquisition and depends on constants derived from the formula for a sphere. The resulting measurement of the LVEDV has about the same error as more complicated methods and allows a rapid estimate of CO (Fig. 57.13).
The exact range of normal for functional parameters of the RVG will depend on multiple factors, such as number of frames acquired, counts within each image, method of computer filtering of the data, and methods of background correction and edge detection. In general, the clinically established normal resting LVEF is approximately 65%, with a standard deviation of 5%. (The normal range of 2 standard deviations is 55% to 75%.)
Left Ventricular Ejection Fraction
The most common causes of elevated LVEF values include mitral or aortic valvular regurgitation, hypertrophic cardiomyopathy, and high cardiac output states such as those found in hyperthyroidism. Low LVEF values are usually seen in patients with prior myocardial infarction, ischemia (with congestive heart failure), or cardiomyopathy of any cause. A common application of the RVG is monitoring for the development of cardiotoxicity from chemotherapeutic drugs.
End-Diastolic Volume
The relative end-diastolic size and shape of the RV and LV chambers (RVEDV and LVEDV) should be always noted. Although they appear roughly equal in a normal best-septal left anterior oblique view, the RVEDV is normally greater than the LVEDV. If no intracardiac shunts are present, the stroke volumes of the ventricles are equal because the RV ejection fraction is smaller than the LVEF. As the LV fails for any reason, it dilates and usually becomes rounder in shape. (See Fig. 57.13 for an example of a dilated LV.)
Wall motion of various regions of the LV can be assessed from an overlay of end-diastolic and end-systolic edge images. This is best evaluated by visually observing a cine display of the beating heart in orthogonal views. The left anterior oblique or best septal view is the critical view, but the anterior and left posterior oblique views are complementary.
As the ventricular wall is damaged or infarcted, the progression of wall motion abnormality is from normal to hypokinetic to akinetic. If an aneurysm forms, the wall will become dyskinetic. This analysis is true for gated SPECT as well as RVG. To determine the degree of abnormality, it is important to concentrate on the margins of the LV chamber, which is the interface of the endocardial surface and blood. The observer should attempt to correlate a

suspicion of abnormal wall motion in one view with this same area on the orthogonal view. Color computer displays that enhance the margins of the chambers may make subtle wall motion abnormalities more easily detectable.
FIGURE 57.13. Sample Calculations of Cardiac Output (CO). Calculation of left ventricular end-diastolic volume (LVEDV) can be done using the count-based ratio method, which requires measurement of the total counts in the end-diastolic region of interest, the maximum pixel counts in the same region of interest, and measurements of the size of a pixel in centimeters. In this case, the dilated LV has a LVEDV of 275 cm3. Multiplication of the LVEDV by the LVEF and heart rate gives a global CO of 10.97 L/min.
Fourier phase analysis provides powerful additional information on the amount of motion (amplitude) of various LV wall segments and also their relative timing (phase). The amplitude image is especially useful for confirming areas suspected to be hypokinetic or akinetic on the cine display. Damaged areas of myocardium contract with less vigor than normal areas. The phase display may help detect such areas because damaged areas contract slowly (tardive kinesis). Dyskinetic, aneurysmal areas are dramatically displayed using Fourier amplitude and phase images. There is wall motion of the segment displayed on the amplitude image, but it is opposite (180° out of phase) compared with undamaged areas (Figs. 57.14, 57.15).
Valvular Regurgitation
Another use of Fourier amplitude images is in the calculation of valvular regurgitation. Each pixel in an amplitude image is coded with a number proportional to the blood volume change under that pixel during the cardiac cycle. A simple total of the pixel values in all the LV and RV pixels outlined with region-of-interest markers will produce a ratio of the LV-to-RV stroke volume. The ratio can be used to calculate the regurgitant fraction. This method works only when there are regurgitant valves on one side of the septum. It cannot distinguish aortic regurgitation from mitral regurgitation, however (Fig. 57.16).
Exercise Radionuclide Ventriculogram
The RVG study can also be done repeatedly while the patient is exercising on a bicycle ergometer at various workload levels. This is an excellent method to monitor cardiac functional response to exercise. The 2- to 3-minute periods for each exercise level usually supply a minimally acceptable amount of statistical counts in the gated images. Finally, a large amount of data must be processed and reviewed because each stage of the study is compared with the resting study (Table 57.1).
The relative cardiac output can be measured from one stage to another and rises with increasing workload. Normal patients increase or augment their LVEF and dV/DT significantly while decreasing their LV end-systolic volume. Abnormal exercise RVG response can be seen in several ways, such as an increase of LVEDV by more than 10%, lack of increase or even a fall in LVEF with greater workloads, and development of wall motion abnormalities caused by ischemia brought on by the exercise.
First-Pass Function Studies
Right ventricular function is more difficult to assess by the RVG study than is LV function. This is because labeled activity in the RV cannot be isolated as well from other chambers as can LV activity. RV function is best assessed by analyzing images from the first pass of a radionuclide


bolus through the right-sided chambers and lungs before the overlapping left-sided chambers are seen. The patient is usually imaged in the right anterior oblique projection. A bolus of up to 30 mCi of high-specific-activity isotope must be very rapidly injected, followed immediately by a nonradioactive flush dose. This activity will pass through the RV in three to eight heartbeats. A region of interest is established around the RV and a time-activity curve allows an RV ejection fraction to be measured for each beat. An average RV ejection fraction is then calculated (Fig. 57.17).
FIGURE 57.14. Normal Fourier Phase and Amplitude Images. These are from the same patient shown in Figs. 57.11 and 57.12. The lower (amplitude) image shows the relative displacement of blood in each chamber of the heart. The pixel brightness depicts the relative degree of motion. The upper (phase) image shows the relative timing of contraction of each chamber. The histogram summarizes the number of pixels with a given phase angle. The cardiac cycle is represented on an arbitrary scale of –90° to 270°. Note that the gray pixels representing ventricular motion are tightly grouped around –30°, indicating synchronous contraction. Approximately 180° up the time scale, there is a cluster of white pixels corresponding to atrial motion.
FIGURE 57.15. Fourier Phase and Amplitude in Left Bundle Branch Block. Two separate populations of phase values are seen in the RV and LV. The lighter-colored RV contracts before the darker-colored LV. This is much easier to see in color.
FIGURE 57.16. Mitral Regurgitation Calculated From a Fourier Amplitude Image. The total counts in the LV and RV regions of interest yield a 1.5:1 LV/RV stroke ratio with a 0.33 regurgitant fraction. This is the same patient imaged in Fig. 57.12. The global cardiac output (CO) of 10.97 is multiplied by the complement of the regurgitant fraction (0.67) to generate a forward CO of 7.35 L/min.
Another good RVEF technique uses xenon-133 in saline solution for injection. During a slow venous infusion, the xenon-133 passes through the right side of the heart and into the lungs, where it immediately fills the alveoli and is exhaled. In this way, overlapping activity never enters the left side of the heart. A gated study over many seconds is acquired and processed in a manner identical to the standard RVG of the LV. In general, an average RVEF is 42%, with a standard deviation of 5% and a normal range of 32% to 52% (Fig. 57.18).
First-Pass Flow Studies
The first-pass study in an anterior projection can also be used to detect abnormalities of blood flow to one lung compared with the other. The effect of extrinsic compression on a pulmonary artery by a mediastinal or hilar mass can be easily detected. Abnormal blood flow to a lung segment

such as is seen in pulmonary sequestration can be detected. The first-pass study can be used to measure the transit time of an injected bolus between ventricles. There is a delay in the passage of blood from the RV to the LV, which typifies congestive heart failure. Obstruction of the superior vena cava is also easily diagnosed in a matter of seconds (Fig. 57.19).
TABLE 57.1 Example of Poor Diastolic Function as Measured by Exercise Radionuclide Ventriculogram-Relative Volumes and Cardiac Output
Rest 78 150 11.7 0.56 1.00 1.00 1.00 1.00
EX1 101 152 15.4 0.60 0.83 0.76 0.89 1.16
EX2 102 158 16.1 0.64 0.90 0.74 1.03 1.35
EX3 106 158 16.7 0.64 0.96 0.79 1.10 1.50
EX4 115 170 19.6 0.68 0.91 0.66 1.11 1.63
EX5 133 190 25.3 0.72 0.77 0.49 1.00 1.70
EX6 153 192 29.4 0.71 0.59 0.39 0.75 1.47
Post-EX 162 162 26.2 0.70 0.69 0.47 0.86 1.79
This exercise radionuclide ventriculogram shows that the patient worked hard during six levels of bicycle exercise (EX1 to EX6) as the heart rate (HR) rose from 78 to 153, while systolic blood pressure (BP) rose from 150 to 192, with a resultant rise in double product (DP) from 11,700 to 29,400. The left ventricular ejection fraction (LVEF) rose appropriately from 0.56 to 0.71 at peak exercise. However, the ventricle filled poorly during exercise as relative end-systolic volume (rLVESV) went progressively down (normal) and relative end-diastolic volume (rLVEDV) also declined (abnormal). The stroke volume (rLVSV) changed little and the only improvement in relative cardiac output (rCO) was the result of increased heart rate. Poor diastolic function (poor compliance) limited exercise endurance in this otherwise healthy individual. This is a superb example of the quantitative data inherent in nuclear medicine images.
FIGURE 57.17. Right Ventricular First-Pass Function Study. A. Fast dynamic right ventricular ejection fraction by first pass. The acquisition totaled 512 frames taken at 40-ms intervals in the right anterior oblique (RAO) projection as a radioactive bolus traversed the RA and RV. An image of the RV is made by summing dozens of individual frames. A fixed region of interest (ROI) is drawn around the RV. SVC, Superior vena cava; PA, pulmonary artery. B. A time-activity curve from the ROI in (A) shows the relative volume of the ventricle rising and falling with diastole and systole. Peaks and valleys in the curve are flagged, and beat by beat ejection fractions are averaged.
FIGURE 57.18. Xenon-133 Right Heart Gated First-Pass Study. Xenon-133 in saline is slowly infused for a gated first-pass study. It is shown with right anterior oblique end-diastolic and end-systolic frames and their respective regions of interest around the RV blood pool. The RV ejection fraction in this patient with congestive heart failure is only 20%.
Left-to-right intracardiac shunts can be detected and quantified using a first-pass imaging technique. Instead of using a region of interest over the RV for analysis, an area

of lung is used. In a normal person, the bolus of activity passes into and out of the lung exponentially in a way that can be mathematically described by a gamma function. If a left-to-right shunt is present, some blood that has gone through the lungs to the left side of the heart reenters the right side of the heart and is pumped back into the lungs. This causes a prolongation of the washout of activity from the lung region of interest. A gamma-variate curve-fitting method can be used to detect and quantify the amount of the left-to-right shunt. The method is sensitive to detect

shunts with a ratio as low as 1.2:1, far below the 2:1 shunt that can be detected by chest radiograph (Fig. 57.20).
FIGURE 57.19. Superior Vena Cava (SVC) Obstruction. A first-pass study with 1-second frames is shown in the anterior projection after injection in the right antecubital vein. Serpiginous collateral veins on the chest wall probably communicate with the intercostal and azygos veins. Very little flow courses through the SVC into the RA and RV (arrow). The patient required stenting of the SVC to relieve obstruction caused by an encircling tumor.
FIGURE 57.20. Abnormal Left-to-Right Shunt Study. A. Regions of interest are drawn around the superior vena cava (SVC, square box) and the right lung (R lung) on image data from a first-pass flow study. Note lack of activity in the LV (arrow) in this summary of images from the right heart phase of the flow. B. Graph showing time-activity curve of the activity within the two regions shown in (A). A is the sharp bolus injection passing through the superior vena cava. B is the right lung time activity curve, which rises exponentially but does not follow the fitted gamma variate curve (C) on the way down. This indicates early recirculation owing to a left-to-right shunt. The shunt is quantified by comparing the area under C with the area under the fitted recirculation gamma variate (D).
FIGURE 57.21. Abnormal Right-to-Left Shunt Study. A significant portion of the injected technetium-99m macroaggregated albumin (MAA) particles are seen in capillary beds outside the lungs in the brain and kidneys. This indicates and measures the amount of shunted blood.
Right-to-left shunts can be detected by using an IV injection of macroaggregated albumin particles. In a normal person, less than 10% of the injected dose should pass through normal arteriovenous shunts in the lungs and be found in the systemic circulation. After injection, static images of the patient’s whole body are obtained. Regions of interest are taken over the lungs, head, neck, abdomen, and extremities. The amount of radioactivity outside the lungs in the systemic circulation is then quantified. The study can be repeated at a later date to check progression (Fig. 57.21).
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