Nuclear Medicine

Cardiac Imaging in Nuclear Medicine 1 B. Leonard Holman, M.D.

With the rapid improvement in instrumentation and radiopharmaceuticals, cardiovascular nuclear medicine has undergone dramatic growth. Radiotracer techniques for the estimation of myocardial blood flow, metabolism and cardiac hemodynamics have been accepted into routine clinical practice. These techniques are also providing sensitive tools to help us elucidate cardiac physiology and pathophysiology. This review explores a number of recent developments in this rapidly changing field. INDEX TERMS: Heart, radionuclide studies, 5[ 1J.1299 Radiology 133:709-716, December 1979 TABLE I:

N 1927, Blumgart and Weiss used radon gas to mea-


sure intravascular transit times in patients with congestive failure (1). These classic studies paved the way for the development of radiotracer techniques to measure other indices of cardiovascular function. The full potential of this powerful technique has only recently been realized. With the development of improved instrumentation and radiopharmaceuticals, there has been a rapid development of radiotracer techniques for the estimation of myocardial blood flow, metabolism and cardiac hemodynamics. In this review, I will explore a number of areas in which radiotracer techniques will play an increasingly important role as a research probe into the cardiovascular system and as a diagnostic tool in clinical practice.



Advantages Rapid Low background Temporal separation of cardiac chambers Quantification of l -- R shunts

1. 2. 3.

Disadvantages Count rate limited Reinjection of tracer for each additional study Increasing background with each additional study

1. 2.






There are two general types of radionuclide techniques for assessing ventricular performance. First-pass techniques measure indices of cardiac performance from the initial transit of the radiotracer through the heart. Equilibrium studies measure ventricular function using radiotracers that have reached equilibrium in the intravascular space.


11C-palmitate 11C-glucose 18F-deoxyfluoroglucose

Assessment of regional myocardial metabolism (28,29)

20 min

13NH 4 + 82Rb

Perfusion tomography (30) Sequential myocardial perfusion imaging (31)

10 min 1.25 min (from 82Sr: 25 T1 / 2 days) 2 min

Quantification of regional myocardial blood flow and regional oxygen utilization (32)


2 hr


also been suggested for first-pass studies. Tantalum-178, a new short-lived radiotracer (T1/2 = 9.3 minutes; 56-64 keV), obtained as a generator product from its long-lived (21.3-day) parent tungsten-178 may alleviate some of these problems (4-7). The radiopharmaceutical for equilibrium (ECG-gated) studies must remain in the intravascular space throughout the course of the study. If continual monitoring is anticipated, the radiopharmaceutical must remain within the intravascular space for at least one half-life. 99mrc-human serum albumin (HSA) and 99mTc-tagged red blood cells (RBCs)have been advocated for this purpose. 99mTc-HSA

The radionuclide usually used for first-pass radionuclide angiocardiography is technetium-99m-pertechnetate. The major disadvantage of 99mrc is its long half life (T1/2 = 6h) relative to the time of the procedure. After intravenous injection, 99mrc-pertechnetate remains in the intravascular and extracellular space, precluding serial studies. Only two or three studies are possible within a six-hour period. As a result, evaluation in multiple projections or after multiple physiologic or pharmacologic interventions is not possible. Other 99mrc pharmaceuticals with more rapid blood clearance (99mrc-DTPA or 99mrc-sulfur colloid) (2, 3) have

1 From the Department of Radiology, HarvardMedical School, Boston, MA 02115. From the Symposium on Advances in the Diagnosisof Cardiac Disease given at the Sixty-fourth Scientific Assembly and Annual Meeting of the Radiological Society of North America, Chicago, IL, Nov. 26-Dec. 1, 1978. Submitted for publication 21 Feb. 1979; revision requested 5 June; accepted 24 July 1979. shan




December 1979





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Fig. 1.

Data are acquired in frames temporally gated to the electrocardiogram.

is less satisfactory for gated studies because (a) there is proportionately more activity in the liver since the liver albumin space is larger than the intravascular space and (b) the blood clearance of 99mTc-HSA is fairly rapid, precluding prolonged monitoring and restudies. 99mTc-RBCs have very slow blood clearance once the initial equilibration of the tracer has been reached. The red cells can be tagged in vivo by injecting commercially available unlabeled (cold) pyrophosphate containing 300-400 Jlg [20-25 mCi or 740-900 MBq] of stannous ion intravenously and injecting 99mTc-pertechnetate 15 minutes later (8, 9). Equilibration is reached after five minutes. Since rapid renal clearance is a precondition for optimal studies, this technique is less satisfactory in patients with poor renal clearance, resulting in high background activity and poor target-to-background ratios. The primary advantage of this technique is the ease with which the red cells can be labeled.

First- Transit Techniques After the intravenous injection of the radiotracer, the bolus passes initially through the right heart, then the lungs, and finally returns to the left atrium and left ventricle. The time-activity curve generated from the left ventricular activity is made up of a series of oscillations. The count rate at the peak in the oscillation is proportional to blood volume at end-diastole and count rate at the valleys is proportional to end-systolic volume. Since the difference in counting rate between end-diastole and end-systole is proportional to stroke volume, the ejection fraction can be obtained by dividing that number by the end-diastolic count rate minus background (determined from regions directly adjacent to the left ventricle): · t' Etee Ion

t: tl End Diastolic Counts - End Systolic Counts rrec Ion = - - - - - - - - - ' - - - - - -

End Diastolic Counts - Background Counts




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Fig. 2. Schematic representation of a normal (left) and hypokinetic (right) left ventricle (transaxial section). The change in counts between end-diastole (outer diameter) and end-systole (inner diameter) is recorded as an intensity on the film (bottom). Normokinetic regions result in high count rate changes and high intensity on the film; asynergic regions result in less change in count rate and a lower intensity.

Regional wall motion can be evaluated by subjective analysis of the cineangiocardiogram constructed from the corrected left ventricular time-activity curve. Each of three to six successive cardiac cycles is divided into 16 frames and the corresponding frames of each cycle are added together to yield one summated or composite cardiac cycle (10). The composite image is played back repetitively producing a cine display of left ventricular motion. While the correlation has been excellent between left ventricular ejection fraction obtained with this technique and with contrast ventriculography (3, 10-12), regional wall motion can be assessed effectively only with high sensitivity instruments such as the multi-crystal camera (TABLE I).

Right Ventricular Ejection Fraction Right ventricular performance has been difficult to quantitate. The geometry of the right ventricle is complex and calculation of right ventricular ejection fraction by standard geometric methods has proved extremely difficult. A radionuclide method for the measurement of right ventricular ejection fraction has been developed using first-transit techniques and is similar in many respects to the measurement of left ventricular ejection fraction (13). A high frequency time-activity curve (25 frames/sec) is generated from both the right ventricular and background regions of interest. Right ventricular ejection fraction is calculated by dividing the difference in counts between end-diastole and end-systole by the number of counts at end-diastole after correcting for background. Normal right ventricular ejection fraction ranges from .44 to .60 (13). This technique has been useful for assessing right ventricular function in patients with acute myocardial infarction and in those with pulmonary disease and suspected cor pulmonale (14). Right ventricular ejection fraction can also be measured


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Nuclear Medicine

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Fig. 3. a. Normal ejection shell divided into anteroseptal, apical and inferoposterior regions . b. Corresponding normal ejection fraction image. [From Maddox DE et af. (18) with permission of the authors and publisher .] Fig. 4. a. Schematic representation of left ventricular ejection shell with thinning (hypokinesis) and fracture (akinesis). b. Corresponding ejection fraction image in a patient with a large akinetic segment (apical) and adjacent hypokinesis. [From Maddox DE et af. (18) with permission of the authors and publisher .]

from the equilibrium radionuclide ventriculogram using multiple regions of interest (15) or a slant hole collimator (45 0 left anterior oblique projection plus a 30 0 caudal tilt) and a single region of interest.

Equilibrium (Gated) Techniques Equilibrium radionuclide ventriculography overcomes several limitations of the first-pass technique. Only one injection is required for serial studies in multiple projections or under various physiologic or pharmacologic interventions. High count rates can be obtained resulting in high spatial resolution. Equilibr ium ventriculography has a number of inherent limitations of its own, however. Activity is present in all four cardiac chambers as well as in the great vessels, making evaluation of the left ventricle dif-

ficult and highly dependent upon patient position. Also. background is high, representing more than 50 % of the activity emanating from the region of the left ventricle. Equilibrium angiocardiography uses both a physiologic marker and time to determine the order in which activity will be displayed. Acquisition is gated to a marker (usually the R wave) of the electrocardiogram (Fig. 1).The resultant study represents the change in radioactivity that occurs within the vascular chambers during the cardiac cycle. Since the change in activity is proportional to the change in blood volume, a relative volume curve can be obtained from the left ventricle when background corrections have been performed. The volume curve represents the average change in blood volume when all the cardiac cycles acquired during the study have been summed. For subjective visual assessment of wall motion and





December 1979


[email protected]~ln AORTIC VALVE




Fig. 5. a. Schematic representation of normal transaxial emission computed tomography of the heart with 201T1. b. Transaxial ECT with thallium-201 in man. The distribution throughout the left ventricular wall is uniform .

chamber size, a radionuclide cineangiogram is created from the equilibrium study using low temporal resolution (9-20 frames per cardiac cycle) (16, 17) so that the composite cardiac cycle can be replayed within a time frame corresponding to a cardiac cycle. The frames are played in a dynamic mode to achieve cine representation of the cardiac cycle. The cycle is played over and over to simulate the appearance of the beating heart. While low temporal resolution is required for construction of the cine mode radionuclide angiocardiogram, high temporal resolution (40-60 frames/cycle) is required to produce the quantitative hemodynamic information obtained from the left ventricular volume curve . Left ventricular ejection fraction is obtained from the background corrected left ventricular time-activity curve, much as in the first-pass study. Correlation between the two methods is high (2). While regional wall motion can be evaluated subjectively by analysis of the cineangiocardiogram, quantitative analysis is possible from either the ejection fraction image or quantitative measures of regional ejection fraction . The ejection fraction image and regional ejection fraction measurements make use of the proportionality between the background corrected left ventricular count rate and blood volume (Fig. 2). For the ejection fraction image, the background corrected end-systolic image is subtracted from the background corrected end-diastolic frame, producing an image of relative stroke volume. The relative stroke volume (difference) image is then divided by the end-diastolic frame producing an ejection fraction image, a map of regional ejection fractions throughout the left ventricle. In the ejection fraction image the intensity of the matrix areas is directly proportional to regional ejection fraction. The normal ejection fraction image is charac terized by a peripheral ejection shell comprised of matrices with gr'eater than 50% ejection (Fig. 3). Thinning of the ejection shell corresponds to regional hypokinesis and fracture of the shell corresponds to an akinetic wall segment (Fig. 4). There is excellent agreement between abnormalities in the ejection fraction image and regional wall motion abnormalities as determined from contrast ventriculography (18). Further quantitation is possible by dividing the enddiastolic left ventricular perimeter into regions and determining the ejection fraction from each of these areas (19). Comparison of regional ejection fraction demonstrated significant differences between regions with roentgenographically determined normokinesis (75 ± 3 %,

Cardiac imaging in nuclear medicine.

Nuclear Medicine Cardiac Imaging in Nuclear Medicine 1 B. Leonard Holman, M.D. With the rapid improvement in instrumentation and radiopharmaceutical...
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