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Nongeometric determination of right ventricular volumes from equilibrium blood pool scans
Nongeometric Determination of Right Ventricular Volumes From Equilibrium Blood Pool Scans
GREGORY J. DEHMER, MD BRIAN G. FIRTH, MD, DPhil L. DAVID HILLIS, MD, FACC PASCAL NICOD, MD JAMES T. WILLERSON, MD, FACC SAMUEL E. LEWIS, MD Dallas, Texas
From the Department of Internal Medicine (Cardiovascular Division) and Radiology (Nuclear Medicine), University of Texas Health Science Center and Parkland Memorial Hospital. Dallas, Texas. This work was supported by the lschemic SCDR Grant HL-17669 from the National Institutes of Health, Bethesda, Maryland, and the Harry S. Moss Heart Fund, Dallas, Texas. Manuscript received April 29, 1981; revised manuscript received July 1, 1981, accepted July 15, 1981. Address for reprints: L. David Hillis, MD, Room L5 134, University of Texas Health Science Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235.
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It has previously been shown that left ventricular volumes can be measured accurately from radionuclide gated blood pool scintigrams by quantitating the background-corrected and volume-normalized ventricular activity at end-diastole and end-systole. To determine if this same technique can be applied to the calculation of right ventricular volumes, simultaneous measurements of right ventricular stroke volume were performed using gated scintigraphy and the thermodilution technique in 60 patients without clinical or hemodynamic evidence of right-sided regurgitation. Three techniques for the acquisition of the radionuclide studies were evaluated. The best correlation between scintigraphic and thermodilutlon determinations of stroke volume was obtained for studies acquired with a 25’ rotating slant hole collimator positioned in a 10 to 15“ left anterior oblique projection with the collimator slant directed toward the cardiac apex along the axis of the interventricular septum: Thermodilution stroke volume = 4.2 (scintigraphic stroke volume) -I- 10.3 ml (correlation coefficient [r]= 0.66; standard error of the estimate = 9.3 ml; probability [p]
An assessment of right ventricular function can provide useful information in patients with cardiac as well as noncardiac diseases.‘-‘0 Several techniques have been employed for the measurement of right ventricular volumes and ejection fraction. The indicator-dilution methodll was initially utilized, but it has now been replaced by more reliable methods. Contrast angiography can be used, 12-17 but this method is invasive (and therefore involves some risk to the patient) and requires that certain geometric assumptions be made concerning the shape of the right ventricle. Several noninvasive methods have been used to evaluate right ventricular function. M mode echocardiographic images of the right ventricle have been difficult to record and interpret because of this chamber’s eccentric shape and its location within the thorax. Although two dimensional echocardiography appears promising in the assessment of right ventricular function,18 use of this method has not been extensively evaluated. Finally, right ventricular ejection fraction (but not
January1982 The AmericanJournalof CARDIOLOGY Volume49
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volumes) has been quantitated by several radionuclide techniques, including first pass,6 gated first pass1g-21 and equilibrium scintigraphy.gJO These radionuclide methods are noninvasive and are “count based,” so that ejection fraction can be estimated independently of assumptions about the complex geometry of the right ventricle. However, radionuclide techniques have not previously allowed the quantitation of right ventricular volumes. Recently, we used the count data derived from gated equilibrium blood pool scans to determine absolute left ventricular volumes and have validated this method by correlations with both angiographically determined end-diastolic and end-systolic volumes22 as well as thermodilution-determined stroke volumes.23 Additional evaluations of this technique were performed independently by others with similar results.2P27 The purpose of this report is to describe the application and validation of this scintigraphic technique to the quantitation of right ventricular volumes.
Methods Study patients: Gated equilibriumblood pool imaging was performed during routine cardiac catheterization in 74 patients (47 men and 27 women with a mean age of 50 years).
FffiURE 1. Enddiastolic and end-systolic images from gated blood pool scans for the three imaging methods. Three imaging methods were employed (see text for details) using parallel hole (method 1) and slant hole (methods 2 and 3) collimators. Outlines of the right ventricular end-diastolic and end-systolic regions of interest are shown. Note that method 3 provides the best separation of the right atrium from the right ventricle.
RIGHT VENTRICULAR
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ET AL.
Catheterization was performed to evaluate chest pain of uncertain origin in 26 patients, some sequelae of ischemic heart disease in 41, aortic stenosis in 4, cardiomyopathy in 2 and constrictive pericardial disease in 1. In all patients careful physical examination revealed no evidence of pulmonary or tricuspid valve regurgitation. For the 74 patients, the right atria1 mean pressure averaged 5.5 f 3.2 mm Hg (mean f standard deviation) (range 1 to 20 mm Hg), with V waves averaging 5.8 f 3.4 mm Hg (range 1 to 22); the average pulmonary arterial systolic pressure was 27.5 f 8.1 mm Hg (range 14 to 65). Intracardiac oximetry revealed no evidence of a shunt. Thermodilution cardiac output measurements: Right heart catheterization was performed with a flow-directed balloon-tipped thermodilution catheter (Electronics for Medicine thermodilution catheter 620037) advanced to the pulmonary artery under fluorosco ic control. At 90 second intervals, bolus injections of steril J saline solution (10 ml at O” C) were introduced into the I’;ght atrium through the catheter’s proximal lumen, and the resultant change in temperature at the thermistor was recorded. Cardiac output was calculated with a miniature analog computer system (Electronics for Medicine model DTCCO-06/V2212).2831 Multiple thermodilution measurements of cardiac output were made during the radionuclide study, and the average of three to five determinations was used for the final correlation. For the 74 patients, the variability of thermodilution cardiac output measurements was 4.5 f 2.5 percent. Stroke volume was calculated by dividing cardiac output by the average heart rate during data acquisition. Multigated equilibrium blood pool scintigraphy: Red blood cells were labeled with 30 mCi of technetium-99m pertechnetate using a technique combining features of both in vitro and in vivo labeling.2s Data collection was performed with a portable gamma scintillation camera (Series Sigma 420, Ohio Nuclear) interfaced to a dedicated computer system (Series 550, Ohio Nuclear). All studies were gated for 32 frames/cardiac cycle and collected for 100 percent of the cardiac cycle. Image sets were acquired for a predetermined number of cardiac cycles so that the total acquisition time was approximately 7 minutes. This resulted in a minimum of 150,000 counts/frame. All data were stored on magnetic discs for subsequent analysis. The accuracy of count-based estimates of ventricular volume and ejection fraction derived from radionuclide gated blood pool images is highly dependent on projection angle. Ventricular activity must be separated from nonventricular contaminating activity. In most cases left ventricular activity can be adequately separated by some combination of left anterior oblique and caudai anguiation of the detector. However, anatomic considerations suggest that the separation of right ventricular activity from right atria1 activity is more difficult. Determination of right ventricular ejection fraction from gated blood pool images has been accomplished with both straight boregJO and slant hole collimators,32 and it has been suggested that slant hole studies provide better separation of the right-sided chambers. In the present study we evaluated three imaging techniques in an attempt to identify the one that would provide the best separation of right ventricular activity from right atria1 and periventricular background activity. Twenty consecutive patients were studied with each of these three methods. Representative examples of images obtained with these methods are displayed in Figure 1. Method 1: Scintigrams were acquired with a low energy all purpose parallel hole collimator. The detector was positioned so as to provide optimal visualization of the interventricular
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septum. The degree of left anterior obliquity required was usually between 30 and 50’. In addition, the detector was angled 10 to 15’ caudally so as to improve the separation between atria and ventricles. This method is similar to that employed by Maddahi et a1.gand Slutsky et al.‘0 for the calculation of right ventricular ejection fraction. In addition, this is the projection we22,23have used for the calculation of left ventricular volumes. Method 2: Scintigrams were obtained with a low energy 25’ slant hole collimator. The detector was positioned in a 30 to 50” left anterior oblique projection so as to provide optimal visualization of the septum, as previously described. The slant of the collimator was parallel to the long axis of the body and directed caudally. This projection is similar to that described by Holman et a1.32 Method 3: Scintigrams were acquired with a low energy 25” slant hole collimator. The detector was positioned so as to provide clear separation of the ventricle while maximizing visualization of the right atrium. This was usually achieved with the detector in a 5 to 15’ left anterior oblique projection. The slant of the collimator was directed toward the cardiac apex parallel to the long axis of the septum. This was usually achieved by rotating the collimator 7 to 21’ from the long axis of the body. This projection has not been described previously but does appear to improve the separation of the right-sided
chambers.
Scintigraphic volume measurements: The first frame of the gated sequence was designated as the end-diastolic frame. The end-systolic frame was determined from the right ventricular time-activity curve. These two frames were smoothed with a nine point center-weighted filter. Background correction was performed by a linear interpolated subtraction technique originally described by Goris et a1.33 and modified for gated blood pool images by Dehmer et a1.23 Separate right ventricular regions of interest were constructed for the end-diastolic and end-systolic frames. The importance of this approach, in contrast to a fixed end-diastolic region of interest, has been emphasized.g The two frames were displayed in an endless loop movie format to assist in the definition of the ventricular borders. Identification of the atrioventricular border was assisted by visualizing the inward motion of the lateral right ventricular wall during systole, and the plane of the pulmonary valve was chosen as the junction between the contracting and noncontracting regions of the outflow tract. If the pulmonary valve plane could not be identified, the upper boundary of the right ventricle was defined by a line connecting the upper border of the interventricular septum to the angle between the inferior border of the ascending aorta and the lateral border of the pulmonary outflow tract. Lateral and septal right ventricular borders were easily identified using all three imaging methods. The number of counts within the end-diastolic and end-systolic regions of interest was determined and used for the calculation of volume. The rationale and equation for the scintigraphic estimation of left ventricular volumes has previously been described.22J3 An identical approach was used for the estimation of right ventricular volumes. The following equation was used for the scintigraphic estimation of right ventricular volumes: Scintigraphic volume estimate = Background corrected ventricular counts Total acquisition time/frame
[s]
Peripheral blood activity (counts/ml/s)
X emAt,
e-kt is the general expression for isotope decay, x = 0.693/Tl12, t = time (in minutes) from counting the peripheral
where
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January1982 The American Journal of CARDIOLOGY
blood sample to the midpoint of the gated study, and T1/2 for technetium-99m is 360 minutes. Because of the attenuation provided by the chest wall, scintigraphic volume estimates are consistently smaller than the actual volumes and are therefore expressed as volume units rather than in milliliters. The “volume units” are subsequently converted to milliliters by means of the regression equation derived by relating these units to the stroke volume (in milliliters) measured by the thermodilution method. Scintigraphic estimates of right ventricular stroke volume were calculated using the stroke counts (obtained by subtracting end-systolic from end-diastolic counts). Scintigraphic ejection fraction measurements: For each of the three equilibrium methods, right ventricular ejection fraction was calculated using the formula (EDC - ESC)/EDC, where EDC = end-diastolic counts and ESC = end-systolic counts. The validity of the ejection fraction measurements made by techniques similar to methods 1 and 2 has previously been established.gJ0,32 Right ventricular ejection fractions determined using method 3 were compared with those determined with a gated first pass technique1g-21 in 14 patients in whom the two measurements were obtained within 5 minutes of each other. With use of the right ventricular ejection fraction (EF) and stroke volume (SV) obtained with equilibrium method 3, end-diastolic volume (EDV) was derived from the formula EDV = SVIEF, and end-systolic volume was obtained by subtracting SV from EDV.
Results Stroke volume measurements: Method 1: For the 20 patients in this group, thermodilution-determined stroke volumes ranged from 42 to 106 ml (Fig. 2, left panel). Scintigraphic estimates of right ventricular stroke volume ranged from 4.97 to 23.99 units and correlated satisfactorily with the thermodilution measurements (correlation coefficient [r] = 0.70; standard error of the estimate [SEE] = 11.6 ml; probability [p]
Volume 49
SCINTIGRAPHIC
RIGHT METHOD
VENTRICULAR
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FIGURE 2. Relation between scintigraphic (scan) and thermodilution right ventricular stroke volumes in milliliters (ml) for the three scintigraphic methods. See text for details.
= 4.2 (scintigraphic volume) +10.3 ml. For this method, mean interobserver variability was 5.3 f 5.1 percent (range 1 to 18) and mean intraobserver variability was 4.6 f 8.8 percent (range 0 to 35). Prospective evaluation of method 3: Because method 3 provided the best estimate of right ventricular stroke volumes, it was evaluated prospectively in an additional 14 patients. Scintigraphic stroke volume estimates were corrected using the regression equation for method 3 and were compared with stroke volumes determined simultaneously by the thermodilution technique (Fig. 3). There was excellent agreement between the two methods (r = 0.96; SEE = 4 ml; p
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This study describes and validates the preliminary experience with a technique for determining right ventricular stroke volume from the time-activity data
.
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is
Discussion
2
3
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to gated first pass ejection fraction was: Gated first pass = 0.99 equilibrium -0.019. Calculation of right ventricular end-diastolic and end-systolic volumes: With use of the scintigraphic estimates of stroke volume and the “countbased” right ventricular ejection fraction, it is possible to derive estimates of right ventricular end-diastolic and end-systolic volumes. The absolute volumes calculated in this manner for the 20 patients studied with method 3 are listed in Table I. Right ventricular end-diastolic and end-systolic volumes ranged from 350 and 315 ml, respectively, in a patient with congestive cardiomyopathy to 79 and 42 ml, respectively, in a patient with constrictive pericarditis.
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RVEF
FIGURE 3. Relation between scintigraphic and thermodilution stroke volumes in 14 patients studied prospectively with method 3. Scintigraphic volume units have been corrected using the regression equation determined for method 3. There is excellent agreement between the two methods (r = 0.96; SEE = 4 ml; p
.
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040
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FIGURE 4. Relation between right ventricular ejection fraction (RVEF) determined by gated first pass and equilibrium gated techniques in 14 patients studied with method 3. There is excellent agreement between the techniques: gated first pass = 0.99 equilibrium -0.019; r = 0.94; SEE = 0.027; p
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SCINTIGRAPHICRIGHT VENTRICULAR VOLUMES-DEHMER ET AL
I
TABLE Absolute Volumes
Right Ventricular (method 3)
End-Diastolic
and End-Systolic
Right Ventricular Measurements
Case
6 7
a 9 10
::
:: 15 16 :I: ::
Diagnosis Chest pain; no CAD Cardiomyopathy Recent IMI Recent IMI Chest oain: no CAD CAD CAD Chest pain; no CAD CAD Constrictive pericarditis CAD Chest pain; no CAD Recent IMI Aortic stenosis CAD Aortic stenosis CAD CAD CAD Chest pain; no CAD
Scan SV Estimate (ml)
EF
EDV (ml)
ESV (ml)
46
0.47
98
52
35
0.10
57 :8
0.44 0.54 0.46
130 148 207
73 68 112
0.47 0.69 0.51
157
a3
3: 97
1::
ii
0.46 0.47
170 79
92 69
0.42 0.63
219 110
127 41
73 70 79 48 64 54 57 61
0.29 0.70 0.70 0.53 0.52 0.33 0.61 0.53
252 100 113
179
315
1:; 164 93 115
zs 43 1;: 36 54
CAD = coronary artery disease; EDV = end-diastolic volume; EF = ejection fraction; ESV = end-systolic volume; IMI = inferior myocardial infarction: SV = stroke volume.
derived from gated equilibrium blood pool scans. With use of this established relation and the right ventricular ejection fraction, right ventricular end-diastolic and end-systolic volumes can be estimated. Methods of right ventricular volume estimation: Several techniques have previously been used to evaluate right ventricular performance. Initial attempts with the indicator-dilution technique’l have been shown to overestimate actual volumes.34 Angiographic methods for estimating right ventricular volumes and ejection fraction have been described and validated,12-l7 but contrast angiography has several disadvantages. First, it is an invasive procedure. As a result, it involves some risk and discomfort, and it is not suitable for serial evaluations. Second, because the right ventricle has an eccentric shape, biplane cineangiography is required, and the mathematical formulas for the calculation of volumes are complex and require assumptions about the geometry of the ventricle. Finally, echocardiographic methods have been employed for the evaluation of right ventricular structure and size,ls but the determination of absolute volumes and ejection fraction cannot now be performed with this technique. Radionuclide methods to evaluate right ventricular function: Recently, several radionuclide techniques have been used to evaluate right ventricular function. Right ventricular ejection fraction may be
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calculated by first pass,6 gated first passls-21 and gated equilibrium blood pool techniques.sJO For each of these, changes in right ventricular activity are directly proportional to blood volume; thus, problems arising from the irregular shape of the right ventricle are avoided. However, anatomic differences between the right and left ventricles may make the assessment of right ventricular function using equilibrium techniques difficult. In spite of the potential problems associated with the equilibrium method, satisfactory measurements of right ventricular ejection fraction have been made.sJ0J2 These anatomic problems are avoided with first pass studies, because the right ventricle can be separated both temporally and spatially from the surrounding cardiac structures. However, the calculation of right ventricular volumes by a first pass technique would probably require biplane images and complicated formulas similar to those employed for contrast angiography. Recently, we22,23 and others24-26 have developed the methodology for calculating left ventricular volumes from the time-activity data derived from gated equilibrium blood pool scans. The present study describes the application of this scintigraphic technique to the estimation of right ventricular volumes. Because the angiographic calculation of end-diastolic and end-systolic volumes of the right ventricle is cumbersome and not as well defined as that of the left ventricle, validation of this new scintigraphic technique was performed by a correlation with thermodilution measurements of right ventricular stroke volume. Reliability of method: Several factors could possibly affect the validity and reliability of this study. Although the accuracy of the thermodilution technique is well established,27m30 right ventricular stroke volumes calculated with this technique could be in error in the presence of right-sided valve regurgitation or intracardiac shunting. To exclude these possibilities, several precautions were taken. First, careful auscultation was performed in all patients to ascertain that no murmurs of pulmonary or tricuspid regurgitation were present. Second, intracardiac oximetry was performed in all patients, and none had findings suggestive of an intracardiac shunt. Finally, right-sided pressures were measured in all patients. Although a few patients had moderate pulmonary hypertension or elevated right atria1 pressures, the majority had completely normal pressure measurements. In addition, the group studied consisted mostly of patients with coronary artery disease or chest pain without coronary disease, subjects in whom right-sided regurgitation would be unlikely. For the determination of right ventricular volumes with this scintigraphic technique, it is important to optimize the separation of the right ventricle from the surrounding structures. Accordingly, three different imaging methods were evaluated. Method 1, utilizing a parallel hole collimator positioned in a modified left anterior oblique projection, has been used by others to calculate right ventricular ejection fractiongJO and is the method used to acquire images for the calculation of left ventricular volumes.22l23 Although there is a relation
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between scintigraphic measurements obtained with this method and those obtained with the thermodilution technique, the y intercept of the regression equation is large, probably reflecting persistent contamination of the right ventricle by right atria1 and other noncardiac activity. Previous studies have suggested that imaging with a slant hole collimator may better separate atria1 and ventricular activity.31J5 Therefore, method 2 used a slant hole collimator positioned in a left anterior oblique projection that best defined the interventricular septum. With this method a weak correlation was obtained, but the y intercept was again large. Therefore, in an attempt to isolate the right ventricle more clearly, method 3 used a a slant hole collimator positioned in a 10 to 15” left anterior oblique projection, with the slant holes directed toward the cardiac apex. This method provided the best correlation between scintigraphic and thermodilution measurements of stroke volume. The y intercept was smaller than that of the other methods, providing indirect evidence that there was good isola-
ET AL
tion of the right ventricle from surrounding structures. In addition, the standard error of the estimate and observer variability were acceptable. The regression equation established for method 3 relates scintigraphic right ventricular “stroke volume” (in units) to the true right ventricular stroke volume (in milliliters), as measured by the thermodilution technique. With use of the “count-based” right ventricular ejection fraction, right ventricular end-diastolic and end-systolic volumes can be determined. Clinical applications: Because an assessment of right ventricular function can provide useful informatioti in patients with cardiac and noncardiac diseases, the noninvasive quantitation of right ventricular volumes and ejection fraction with this technique may be extremely useful. Acknowledgment The expert technical help of Sarah Hawkins, Nancy Smith, Randy Christian, R. Scott Lyons and Carl Sorenson is recognized, and the secretarial help of Juanita Alexander is appreciated.
References 1. Fisher EA, DuBrow IW, Hasterreiter AR. Right ventricular volume in congenital heart disease. Am J Cardiol 1975;36:67-75. 2. Rapaporl E, Wong M, Ferguson RE, Bernstein P, Wiegand BD. Right ventricular volumes in patients with and without heart failure. Circulation 1965;31:531-40. 3. Ferlinz J, Gorlin R, Cohn PF, H&man MV. Right ventricular performance in patients with coronary artery disease. Circulation 1975;52:608-15. 4. Liberthson RR, Boucher CA, Strauss HW, Dinsmore RE, McKusick KA, Pohost GM. Right ventricular function in adult atrial septal defect: preoperative and postoperative assessment and clinical implications. Am J Cardioi 1981;47:56-60. 5. Khaja F, Parker J. Right and left ventricular performance in chronic obstructive pulmonary disease. Am Heart J 1971;82:319-27. 6. Berger HJ, Matthay RA, Loke J, Marshall RC, Goltachalk A, Zaret BL. Assessment of cardiac performance with quantitative radionuclide angiocardiography: right ventricular ejection fraction with reference to findings in chronic obstructive pulmonary disease. Am J Cardiol 1978;41:897-905. 7. Rigo P, Murray M, Taylor DR, et al. Right ventricular dysfunction detected by gated scintiphotography in patients with acute inferior myocardial infarction. Circulation 1975;52:268-74. 8. Matthay RA, Berger HJ, Loke J, Gottschaik A, Zaret BL. Effects of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease: noninvasive assessment by radionuclide angiocardiography. Am J Med 1978;65:903-10. 9. Maddahi J, Berman DS, Matsuoka DT, et al. A new technique for assessing right ventricular ejection fraction using rapid muitiplegated equilibrium cardiac blood pool scintigraphy: Description, validation, and findings in chronic coronary artery disease. Circulation 1979;60:581-9. 10. Slutsky R, Hooper W, Gerber K, et al. Assessment of right ventricular function at rest and during exercise in patients with coronary heart disease: a new approach using equilibrium radionuclide angiography. Am J Cardioi 1980;45:63-71. 11. Frels ED, Rivara GL, Giimore BL. Estimation of residual and enddiastolic volumes of the right ventricle of men without heart disease using the dye-dilution method. Am Heart J 1960;60:898-906. 12. Arcilia RA, Tsal P, Thiienius 0, Ranniger K. Angiographic method for volume estimation of right and left ventricles. Chest 1971; 601446-54. 13. Gentzler RD, Briseili MF, Gauit JH. Angiographic estimation of right ventricular volume in man. Circulation 1974;50:324-30. 14 Reedy T, Chapman CB. Measurement of right ventricular volume
by cineangiofluorography. Am Heart J 1963;66:221-5. 15. Boak JG, Bove AA, Kreuien T, Spann JF. A geometric basis for calculation of right ventricular volume in man. Cathet Cardiovasc Diagn 1977;3:217-30. 16. Ferilnz J. Angiographic assessment of right ventricular volumes and ejection fraction. Cathet Cardiovasc Diagn 1976;2:5-14. 17. Horn V, Muitlns CB, Saffer St, el al. A comparison of mathematical models for estimating right ventricular volumes in animals and man. Clin Cardiol 1979;2:341-7. 18. Bommer W, Weinerl L, Neumann A, Neef J, Mason DT, DeMaria A. Determination of right atrial and right ventricular size by twodimensional echocardiography. Circulation 1979;60:91-100. 19. McKusick KA, Blngham JB, Pohost GM, Strauss HW. The gated first pass radionuclide angiogram: a method for measurement of right ventricular ejection fraction (abstr). Circulation 1978;58:Suppl ll:ll-130. 20. Twieg D, Lewis S, Harper J, Curry GC, Mullins CB, Nixon JV. Assessment of right ventricular function in chronic severe pulmonary hypertension by multiple gated first pass radionuclide angiography (abstr). Circulation 1979;6O:Suppl ll:ll-148. 21. Haroids JA, Grove RB, Bowen RD, Powers TA. Right ventricular function as assessed by two radionuclide techniques: concise communication. J Nucl Med 1981;22:113-5. 22. Dehmer GJ, Lewis SE, Hilils LD, et al. Nongeometric determination of left ventricular volumes from equilibrium blood pool scans. Am J Cardioi 1980;45:293-300. 23. Dehmer GJ, Flrth BG, Lewis SE, Wilierson JT, Hiliis LD. Direct measurement of cardiac output by gated equilibrium blood pool scintigraphy: validation of scintigraphic volume measurements by a nongeometric technique. Am J Cardiol 1981;47:1081-7. 24. Siutsky R, Karllner J, Riccl D, et al. Left ventricular volumes by gated equilibrium radionuclide angiography: a new method. Circulation 1979;60:556-64. 25. Maesle B, Kramer B. Radionuciide determination of left ventricular volume: comparison of counts-based and geometric methods (abstr). Am J Cardiol 1981;47:454. 26. Ong L, Coromilas J, Padmanabhan V, Robblns M, Reiser P, Morrison J. Ventricular volumes by gated equilibrium radionuclide angiography (abstr). Clin Res 1980;28:617A. 27. Links JM, Becker LC, Schlndledecker JG, et al. Determination of absolute left ventricular volume from gated blood pool imaging with an attenuation corrected count rate method (abstr). Am J Cardiol 1980;45:407. 28. Ganz W, Donoso R, Marcus HS, Forrester JS, Swan HJC. A
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29.
30. 31.
32.
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ET AL.
technique for measurement of cardiac output by thermodilution in man. Am J Cardiol 1971;27:392-6. Forrester JS, Ganz W, Diamond G, McHugh T, Choneite DW, Swan HJC. Thermodilution cardiac output determination with a single flowdirected catheter. Am Heart J 1972:83:306-l 1. Gant W, Swan HJC. Measurement of blood flow by thermodilution. Am J Cardiol 1972;20:241-6. Phillips CM, Davlla JC, Sanmarco ME. Measurement of cardiac output by thermal dilution II. A new computer for rapid convenient determinations. Med Res Eng 1970;9:25-9. Holman EL, Wynne J, Zlelonka JS, ldolne JD. A simplified tech-
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nique for measuring right ventricular ejection fraction using the equilibrium radionuclide angiocardiogram and the slant-hole collimator. Radio1 1981;138:429-35. 33. Gorls ML, Daspit SG, McLaughlin P, Krlss JP. Interpolative background subtraction. J Nucl Med 1976;17:744-7 34. Swan HJC. Problems in the measurement of ventricular volumes. UCLA Forum Med Sci 1970;10:185-92. 35. Parker JA, Uren RF, Jones AG, et al. Radionuclide left ventriculogram with the slant hole collimator. J Nucl Med 1977;18:84851.
Volume 49
GREGORY J. DEHMER, MD BRIAN G. FIRTH, MD, DPhil L. DAVID HILLIS, MD, FACC PASCAL NICOD, MD JAMES T. WILLERSON, MD, FACC SAMUEL E. LEWIS, MD Dallas, Texas
From the Department of Internal Medicine (Cardiovascular Division) and Radiology (Nuclear Medicine), University of Texas Health Science Center and Parkland Memorial Hospital. Dallas, Texas. This work was supported by the lschemic SCDR Grant HL-17669 from the National Institutes of Health, Bethesda, Maryland, and the Harry S. Moss Heart Fund, Dallas, Texas. Manuscript received April 29, 1981; revised manuscript received July 1, 1981, accepted July 15, 1981. Address for reprints: L. David Hillis, MD, Room L5 134, University of Texas Health Science Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235.
78
It has previously been shown that left ventricular volumes can be measured accurately from radionuclide gated blood pool scintigrams by quantitating the background-corrected and volume-normalized ventricular activity at end-diastole and end-systole. To determine if this same technique can be applied to the calculation of right ventricular volumes, simultaneous measurements of right ventricular stroke volume were performed using gated scintigraphy and the thermodilution technique in 60 patients without clinical or hemodynamic evidence of right-sided regurgitation. Three techniques for the acquisition of the radionuclide studies were evaluated. The best correlation between scintigraphic and thermodilutlon determinations of stroke volume was obtained for studies acquired with a 25’ rotating slant hole collimator positioned in a 10 to 15“ left anterior oblique projection with the collimator slant directed toward the cardiac apex along the axis of the interventricular septum: Thermodilution stroke volume = 4.2 (scintigraphic stroke volume) -I- 10.3 ml (correlation coefficient [r]= 0.66; standard error of the estimate = 9.3 ml; probability [p]
An assessment of right ventricular function can provide useful information in patients with cardiac as well as noncardiac diseases.‘-‘0 Several techniques have been employed for the measurement of right ventricular volumes and ejection fraction. The indicator-dilution methodll was initially utilized, but it has now been replaced by more reliable methods. Contrast angiography can be used, 12-17 but this method is invasive (and therefore involves some risk to the patient) and requires that certain geometric assumptions be made concerning the shape of the right ventricle. Several noninvasive methods have been used to evaluate right ventricular function. M mode echocardiographic images of the right ventricle have been difficult to record and interpret because of this chamber’s eccentric shape and its location within the thorax. Although two dimensional echocardiography appears promising in the assessment of right ventricular function,18 use of this method has not been extensively evaluated. Finally, right ventricular ejection fraction (but not
January1982 The AmericanJournalof CARDIOLOGY Volume49
SCINTIGRAPHIC
volumes) has been quantitated by several radionuclide techniques, including first pass,6 gated first pass1g-21 and equilibrium scintigraphy.gJO These radionuclide methods are noninvasive and are “count based,” so that ejection fraction can be estimated independently of assumptions about the complex geometry of the right ventricle. However, radionuclide techniques have not previously allowed the quantitation of right ventricular volumes. Recently, we used the count data derived from gated equilibrium blood pool scans to determine absolute left ventricular volumes and have validated this method by correlations with both angiographically determined end-diastolic and end-systolic volumes22 as well as thermodilution-determined stroke volumes.23 Additional evaluations of this technique were performed independently by others with similar results.2P27 The purpose of this report is to describe the application and validation of this scintigraphic technique to the quantitation of right ventricular volumes.
Methods Study patients: Gated equilibriumblood pool imaging was performed during routine cardiac catheterization in 74 patients (47 men and 27 women with a mean age of 50 years).
FffiURE 1. Enddiastolic and end-systolic images from gated blood pool scans for the three imaging methods. Three imaging methods were employed (see text for details) using parallel hole (method 1) and slant hole (methods 2 and 3) collimators. Outlines of the right ventricular end-diastolic and end-systolic regions of interest are shown. Note that method 3 provides the best separation of the right atrium from the right ventricle.
RIGHT VENTRICULAR
VOLUMES-DEHMER
ET AL.
Catheterization was performed to evaluate chest pain of uncertain origin in 26 patients, some sequelae of ischemic heart disease in 41, aortic stenosis in 4, cardiomyopathy in 2 and constrictive pericardial disease in 1. In all patients careful physical examination revealed no evidence of pulmonary or tricuspid valve regurgitation. For the 74 patients, the right atria1 mean pressure averaged 5.5 f 3.2 mm Hg (mean f standard deviation) (range 1 to 20 mm Hg), with V waves averaging 5.8 f 3.4 mm Hg (range 1 to 22); the average pulmonary arterial systolic pressure was 27.5 f 8.1 mm Hg (range 14 to 65). Intracardiac oximetry revealed no evidence of a shunt. Thermodilution cardiac output measurements: Right heart catheterization was performed with a flow-directed balloon-tipped thermodilution catheter (Electronics for Medicine thermodilution catheter 620037) advanced to the pulmonary artery under fluorosco ic control. At 90 second intervals, bolus injections of steril J saline solution (10 ml at O” C) were introduced into the I’;ght atrium through the catheter’s proximal lumen, and the resultant change in temperature at the thermistor was recorded. Cardiac output was calculated with a miniature analog computer system (Electronics for Medicine model DTCCO-06/V2212).2831 Multiple thermodilution measurements of cardiac output were made during the radionuclide study, and the average of three to five determinations was used for the final correlation. For the 74 patients, the variability of thermodilution cardiac output measurements was 4.5 f 2.5 percent. Stroke volume was calculated by dividing cardiac output by the average heart rate during data acquisition. Multigated equilibrium blood pool scintigraphy: Red blood cells were labeled with 30 mCi of technetium-99m pertechnetate using a technique combining features of both in vitro and in vivo labeling.2s Data collection was performed with a portable gamma scintillation camera (Series Sigma 420, Ohio Nuclear) interfaced to a dedicated computer system (Series 550, Ohio Nuclear). All studies were gated for 32 frames/cardiac cycle and collected for 100 percent of the cardiac cycle. Image sets were acquired for a predetermined number of cardiac cycles so that the total acquisition time was approximately 7 minutes. This resulted in a minimum of 150,000 counts/frame. All data were stored on magnetic discs for subsequent analysis. The accuracy of count-based estimates of ventricular volume and ejection fraction derived from radionuclide gated blood pool images is highly dependent on projection angle. Ventricular activity must be separated from nonventricular contaminating activity. In most cases left ventricular activity can be adequately separated by some combination of left anterior oblique and caudai anguiation of the detector. However, anatomic considerations suggest that the separation of right ventricular activity from right atria1 activity is more difficult. Determination of right ventricular ejection fraction from gated blood pool images has been accomplished with both straight boregJO and slant hole collimators,32 and it has been suggested that slant hole studies provide better separation of the right-sided chambers. In the present study we evaluated three imaging techniques in an attempt to identify the one that would provide the best separation of right ventricular activity from right atria1 and periventricular background activity. Twenty consecutive patients were studied with each of these three methods. Representative examples of images obtained with these methods are displayed in Figure 1. Method 1: Scintigrams were acquired with a low energy all purpose parallel hole collimator. The detector was positioned so as to provide optimal visualization of the interventricular
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septum. The degree of left anterior obliquity required was usually between 30 and 50’. In addition, the detector was angled 10 to 15’ caudally so as to improve the separation between atria and ventricles. This method is similar to that employed by Maddahi et a1.gand Slutsky et al.‘0 for the calculation of right ventricular ejection fraction. In addition, this is the projection we22,23have used for the calculation of left ventricular volumes. Method 2: Scintigrams were obtained with a low energy 25’ slant hole collimator. The detector was positioned in a 30 to 50” left anterior oblique projection so as to provide optimal visualization of the septum, as previously described. The slant of the collimator was parallel to the long axis of the body and directed caudally. This projection is similar to that described by Holman et a1.32 Method 3: Scintigrams were acquired with a low energy 25” slant hole collimator. The detector was positioned so as to provide clear separation of the ventricle while maximizing visualization of the right atrium. This was usually achieved with the detector in a 5 to 15’ left anterior oblique projection. The slant of the collimator was directed toward the cardiac apex parallel to the long axis of the septum. This was usually achieved by rotating the collimator 7 to 21’ from the long axis of the body. This projection has not been described previously but does appear to improve the separation of the right-sided
chambers.
Scintigraphic volume measurements: The first frame of the gated sequence was designated as the end-diastolic frame. The end-systolic frame was determined from the right ventricular time-activity curve. These two frames were smoothed with a nine point center-weighted filter. Background correction was performed by a linear interpolated subtraction technique originally described by Goris et a1.33 and modified for gated blood pool images by Dehmer et a1.23 Separate right ventricular regions of interest were constructed for the end-diastolic and end-systolic frames. The importance of this approach, in contrast to a fixed end-diastolic region of interest, has been emphasized.g The two frames were displayed in an endless loop movie format to assist in the definition of the ventricular borders. Identification of the atrioventricular border was assisted by visualizing the inward motion of the lateral right ventricular wall during systole, and the plane of the pulmonary valve was chosen as the junction between the contracting and noncontracting regions of the outflow tract. If the pulmonary valve plane could not be identified, the upper boundary of the right ventricle was defined by a line connecting the upper border of the interventricular septum to the angle between the inferior border of the ascending aorta and the lateral border of the pulmonary outflow tract. Lateral and septal right ventricular borders were easily identified using all three imaging methods. The number of counts within the end-diastolic and end-systolic regions of interest was determined and used for the calculation of volume. The rationale and equation for the scintigraphic estimation of left ventricular volumes has previously been described.22J3 An identical approach was used for the estimation of right ventricular volumes. The following equation was used for the scintigraphic estimation of right ventricular volumes: Scintigraphic volume estimate = Background corrected ventricular counts Total acquisition time/frame
[s]
Peripheral blood activity (counts/ml/s)
X emAt,
e-kt is the general expression for isotope decay, x = 0.693/Tl12, t = time (in minutes) from counting the peripheral
where
80
January1982 The American Journal of CARDIOLOGY
blood sample to the midpoint of the gated study, and T1/2 for technetium-99m is 360 minutes. Because of the attenuation provided by the chest wall, scintigraphic volume estimates are consistently smaller than the actual volumes and are therefore expressed as volume units rather than in milliliters. The “volume units” are subsequently converted to milliliters by means of the regression equation derived by relating these units to the stroke volume (in milliliters) measured by the thermodilution method. Scintigraphic estimates of right ventricular stroke volume were calculated using the stroke counts (obtained by subtracting end-systolic from end-diastolic counts). Scintigraphic ejection fraction measurements: For each of the three equilibrium methods, right ventricular ejection fraction was calculated using the formula (EDC - ESC)/EDC, where EDC = end-diastolic counts and ESC = end-systolic counts. The validity of the ejection fraction measurements made by techniques similar to methods 1 and 2 has previously been established.gJ0,32 Right ventricular ejection fractions determined using method 3 were compared with those determined with a gated first pass technique1g-21 in 14 patients in whom the two measurements were obtained within 5 minutes of each other. With use of the right ventricular ejection fraction (EF) and stroke volume (SV) obtained with equilibrium method 3, end-diastolic volume (EDV) was derived from the formula EDV = SVIEF, and end-systolic volume was obtained by subtracting SV from EDV.
Results Stroke volume measurements: Method 1: For the 20 patients in this group, thermodilution-determined stroke volumes ranged from 42 to 106 ml (Fig. 2, left panel). Scintigraphic estimates of right ventricular stroke volume ranged from 4.97 to 23.99 units and correlated satisfactorily with the thermodilution measurements (correlation coefficient [r] = 0.70; standard error of the estimate [SEE] = 11.6 ml; probability [p]
Volume 49
SCINTIGRAPHIC
RIGHT METHOD
VENTRICULAR
STROKE
METHOD
1
1
?? 80 I= 3 60
f:
I
I
5
10
SEE-146ml
I
I
I
45
20
25
f
METHOD
I
+ 450
r =0.49 SEE=409ml
’
’
’
’
’
5
10
15
20
25
3 0 p
60
3
6 ;r
20
..
40
/
y=4 2x + 10.3 n=20 r = 0.88 SEE=93ml
”
L
1
’
5
10
’
’
’
15
20
25
SCAN
SCAN
SCAN
AL
g 80 i=
.
g&x
ET
.
.
g 40 B w 20 i
VOLUMES-DEHMER
VOLUME
0.
*
VENTRICULAR
2
t fl
-300
RIGHT
FIGURE 2. Relation between scintigraphic (scan) and thermodilution right ventricular stroke volumes in milliliters (ml) for the three scintigraphic methods. See text for details.
= 4.2 (scintigraphic volume) +10.3 ml. For this method, mean interobserver variability was 5.3 f 5.1 percent (range 1 to 18) and mean intraobserver variability was 4.6 f 8.8 percent (range 0 to 35). Prospective evaluation of method 3: Because method 3 provided the best estimate of right ventricular stroke volumes, it was evaluated prospectively in an additional 14 patients. Scintigraphic stroke volume estimates were corrected using the regression equation for method 3 and were compared with stroke volumes determined simultaneously by the thermodilution technique (Fig. 3). There was excellent agreement between the two methods (r = 0.96; SEE = 4 ml; p
2
140-
$i
i20IOO-
y i?
80-
. .
l
. 40-
3
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-
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SCINTIGAAPHIC
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60
’
a0 STROKE
.
.*
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c
4 t
f
k
.*
60-
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090
2 oao-
5
P tz
This study describes and validates the preliminary experience with a technique for determining right ventricular stroke volume from the time-activity data
.
p
is
Discussion
2
3
L
to gated first pass ejection fraction was: Gated first pass = 0.99 equilibrium -0.019. Calculation of right ventricular end-diastolic and end-systolic volumes: With use of the scintigraphic estimates of stroke volume and the “countbased” right ventricular ejection fraction, it is possible to derive estimates of right ventricular end-diastolic and end-systolic volumes. The absolute volumes calculated in this manner for the 20 patients studied with method 3 are listed in Table I. Right ventricular end-diastolic and end-systolic volumes ranged from 350 and 315 ml, respectively, in a patient with congestive cardiomyopathy to 79 and 42 ml, respectively, in a patient with constrictive pericarditis.
’
cQ
’
420
VOLUME
2
060-
t 0
OW-
&
040
kl &
030-
.. . . .. .*
-
i ol\t
’
140 (ml)
RVEF
FIGURE 3. Relation between scintigraphic and thermodilution stroke volumes in 14 patients studied prospectively with method 3. Scintigraphic volume units have been corrected using the regression equation determined for method 3. There is excellent agreement between the two methods (r = 0.96; SEE = 4 ml; p
.
’ Ox)
040
.
l
050
c 060
’ 070
BY EOUILIBRIUM
000 GATED
’ 090
10
SCAN
FIGURE 4. Relation between right ventricular ejection fraction (RVEF) determined by gated first pass and equilibrium gated techniques in 14 patients studied with method 3. There is excellent agreement between the techniques: gated first pass = 0.99 equilibrium -0.019; r = 0.94; SEE = 0.027; p
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81
SCINTIGRAPHICRIGHT VENTRICULAR VOLUMES-DEHMER ET AL
I
TABLE Absolute Volumes
Right Ventricular (method 3)
End-Diastolic
and End-Systolic
Right Ventricular Measurements
Case
6 7
a 9 10
::
:: 15 16 :I: ::
Diagnosis Chest pain; no CAD Cardiomyopathy Recent IMI Recent IMI Chest oain: no CAD CAD CAD Chest pain; no CAD CAD Constrictive pericarditis CAD Chest pain; no CAD Recent IMI Aortic stenosis CAD Aortic stenosis CAD CAD CAD Chest pain; no CAD
Scan SV Estimate (ml)
EF
EDV (ml)
ESV (ml)
46
0.47
98
52
35
0.10
57 :8
0.44 0.54 0.46
130 148 207
73 68 112
0.47 0.69 0.51
157
a3
3: 97
1::
ii
0.46 0.47
170 79
92 69
0.42 0.63
219 110
127 41
73 70 79 48 64 54 57 61
0.29 0.70 0.70 0.53 0.52 0.33 0.61 0.53
252 100 113
179
315
1:; 164 93 115
zs 43 1;: 36 54
CAD = coronary artery disease; EDV = end-diastolic volume; EF = ejection fraction; ESV = end-systolic volume; IMI = inferior myocardial infarction: SV = stroke volume.
derived from gated equilibrium blood pool scans. With use of this established relation and the right ventricular ejection fraction, right ventricular end-diastolic and end-systolic volumes can be estimated. Methods of right ventricular volume estimation: Several techniques have previously been used to evaluate right ventricular performance. Initial attempts with the indicator-dilution technique’l have been shown to overestimate actual volumes.34 Angiographic methods for estimating right ventricular volumes and ejection fraction have been described and validated,12-l7 but contrast angiography has several disadvantages. First, it is an invasive procedure. As a result, it involves some risk and discomfort, and it is not suitable for serial evaluations. Second, because the right ventricle has an eccentric shape, biplane cineangiography is required, and the mathematical formulas for the calculation of volumes are complex and require assumptions about the geometry of the ventricle. Finally, echocardiographic methods have been employed for the evaluation of right ventricular structure and size,ls but the determination of absolute volumes and ejection fraction cannot now be performed with this technique. Radionuclide methods to evaluate right ventricular function: Recently, several radionuclide techniques have been used to evaluate right ventricular function. Right ventricular ejection fraction may be
82
January 1992
The American Journal of CARDIOLOGY
calculated by first pass,6 gated first passls-21 and gated equilibrium blood pool techniques.sJO For each of these, changes in right ventricular activity are directly proportional to blood volume; thus, problems arising from the irregular shape of the right ventricle are avoided. However, anatomic differences between the right and left ventricles may make the assessment of right ventricular function using equilibrium techniques difficult. In spite of the potential problems associated with the equilibrium method, satisfactory measurements of right ventricular ejection fraction have been made.sJ0J2 These anatomic problems are avoided with first pass studies, because the right ventricle can be separated both temporally and spatially from the surrounding cardiac structures. However, the calculation of right ventricular volumes by a first pass technique would probably require biplane images and complicated formulas similar to those employed for contrast angiography. Recently, we22,23 and others24-26 have developed the methodology for calculating left ventricular volumes from the time-activity data derived from gated equilibrium blood pool scans. The present study describes the application of this scintigraphic technique to the estimation of right ventricular volumes. Because the angiographic calculation of end-diastolic and end-systolic volumes of the right ventricle is cumbersome and not as well defined as that of the left ventricle, validation of this new scintigraphic technique was performed by a correlation with thermodilution measurements of right ventricular stroke volume. Reliability of method: Several factors could possibly affect the validity and reliability of this study. Although the accuracy of the thermodilution technique is well established,27m30 right ventricular stroke volumes calculated with this technique could be in error in the presence of right-sided valve regurgitation or intracardiac shunting. To exclude these possibilities, several precautions were taken. First, careful auscultation was performed in all patients to ascertain that no murmurs of pulmonary or tricuspid regurgitation were present. Second, intracardiac oximetry was performed in all patients, and none had findings suggestive of an intracardiac shunt. Finally, right-sided pressures were measured in all patients. Although a few patients had moderate pulmonary hypertension or elevated right atria1 pressures, the majority had completely normal pressure measurements. In addition, the group studied consisted mostly of patients with coronary artery disease or chest pain without coronary disease, subjects in whom right-sided regurgitation would be unlikely. For the determination of right ventricular volumes with this scintigraphic technique, it is important to optimize the separation of the right ventricle from the surrounding structures. Accordingly, three different imaging methods were evaluated. Method 1, utilizing a parallel hole collimator positioned in a modified left anterior oblique projection, has been used by others to calculate right ventricular ejection fractiongJO and is the method used to acquire images for the calculation of left ventricular volumes.22l23 Although there is a relation
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between scintigraphic measurements obtained with this method and those obtained with the thermodilution technique, the y intercept of the regression equation is large, probably reflecting persistent contamination of the right ventricle by right atria1 and other noncardiac activity. Previous studies have suggested that imaging with a slant hole collimator may better separate atria1 and ventricular activity.31J5 Therefore, method 2 used a slant hole collimator positioned in a left anterior oblique projection that best defined the interventricular septum. With this method a weak correlation was obtained, but the y intercept was again large. Therefore, in an attempt to isolate the right ventricle more clearly, method 3 used a a slant hole collimator positioned in a 10 to 15” left anterior oblique projection, with the slant holes directed toward the cardiac apex. This method provided the best correlation between scintigraphic and thermodilution measurements of stroke volume. The y intercept was smaller than that of the other methods, providing indirect evidence that there was good isola-
ET AL
tion of the right ventricle from surrounding structures. In addition, the standard error of the estimate and observer variability were acceptable. The regression equation established for method 3 relates scintigraphic right ventricular “stroke volume” (in units) to the true right ventricular stroke volume (in milliliters), as measured by the thermodilution technique. With use of the “count-based” right ventricular ejection fraction, right ventricular end-diastolic and end-systolic volumes can be determined. Clinical applications: Because an assessment of right ventricular function can provide useful informatioti in patients with cardiac and noncardiac diseases, the noninvasive quantitation of right ventricular volumes and ejection fraction with this technique may be extremely useful. Acknowledgment The expert technical help of Sarah Hawkins, Nancy Smith, Randy Christian, R. Scott Lyons and Carl Sorenson is recognized, and the secretarial help of Juanita Alexander is appreciated.
References 1. Fisher EA, DuBrow IW, Hasterreiter AR. Right ventricular volume in congenital heart disease. Am J Cardiol 1975;36:67-75. 2. Rapaporl E, Wong M, Ferguson RE, Bernstein P, Wiegand BD. Right ventricular volumes in patients with and without heart failure. Circulation 1965;31:531-40. 3. Ferlinz J, Gorlin R, Cohn PF, H&man MV. Right ventricular performance in patients with coronary artery disease. Circulation 1975;52:608-15. 4. Liberthson RR, Boucher CA, Strauss HW, Dinsmore RE, McKusick KA, Pohost GM. Right ventricular function in adult atrial septal defect: preoperative and postoperative assessment and clinical implications. Am J Cardioi 1981;47:56-60. 5. Khaja F, Parker J. Right and left ventricular performance in chronic obstructive pulmonary disease. Am Heart J 1971;82:319-27. 6. Berger HJ, Matthay RA, Loke J, Marshall RC, Goltachalk A, Zaret BL. Assessment of cardiac performance with quantitative radionuclide angiocardiography: right ventricular ejection fraction with reference to findings in chronic obstructive pulmonary disease. Am J Cardiol 1978;41:897-905. 7. Rigo P, Murray M, Taylor DR, et al. Right ventricular dysfunction detected by gated scintiphotography in patients with acute inferior myocardial infarction. Circulation 1975;52:268-74. 8. Matthay RA, Berger HJ, Loke J, Gottschaik A, Zaret BL. Effects of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease: noninvasive assessment by radionuclide angiocardiography. Am J Med 1978;65:903-10. 9. Maddahi J, Berman DS, Matsuoka DT, et al. A new technique for assessing right ventricular ejection fraction using rapid muitiplegated equilibrium cardiac blood pool scintigraphy: Description, validation, and findings in chronic coronary artery disease. Circulation 1979;60:581-9. 10. Slutsky R, Hooper W, Gerber K, et al. Assessment of right ventricular function at rest and during exercise in patients with coronary heart disease: a new approach using equilibrium radionuclide angiography. Am J Cardioi 1980;45:63-71. 11. Frels ED, Rivara GL, Giimore BL. Estimation of residual and enddiastolic volumes of the right ventricle of men without heart disease using the dye-dilution method. Am Heart J 1960;60:898-906. 12. Arcilia RA, Tsal P, Thiienius 0, Ranniger K. Angiographic method for volume estimation of right and left ventricles. Chest 1971; 601446-54. 13. Gentzler RD, Briseili MF, Gauit JH. Angiographic estimation of right ventricular volume in man. Circulation 1974;50:324-30. 14 Reedy T, Chapman CB. Measurement of right ventricular volume
by cineangiofluorography. Am Heart J 1963;66:221-5. 15. Boak JG, Bove AA, Kreuien T, Spann JF. A geometric basis for calculation of right ventricular volume in man. Cathet Cardiovasc Diagn 1977;3:217-30. 16. Ferilnz J. Angiographic assessment of right ventricular volumes and ejection fraction. Cathet Cardiovasc Diagn 1976;2:5-14. 17. Horn V, Muitlns CB, Saffer St, el al. A comparison of mathematical models for estimating right ventricular volumes in animals and man. Clin Cardiol 1979;2:341-7. 18. Bommer W, Weinerl L, Neumann A, Neef J, Mason DT, DeMaria A. Determination of right atrial and right ventricular size by twodimensional echocardiography. Circulation 1979;60:91-100. 19. McKusick KA, Blngham JB, Pohost GM, Strauss HW. The gated first pass radionuclide angiogram: a method for measurement of right ventricular ejection fraction (abstr). Circulation 1978;58:Suppl ll:ll-130. 20. Twieg D, Lewis S, Harper J, Curry GC, Mullins CB, Nixon JV. Assessment of right ventricular function in chronic severe pulmonary hypertension by multiple gated first pass radionuclide angiography (abstr). Circulation 1979;6O:Suppl ll:ll-148. 21. Haroids JA, Grove RB, Bowen RD, Powers TA. Right ventricular function as assessed by two radionuclide techniques: concise communication. J Nucl Med 1981;22:113-5. 22. Dehmer GJ, Lewis SE, Hilils LD, et al. Nongeometric determination of left ventricular volumes from equilibrium blood pool scans. Am J Cardioi 1980;45:293-300. 23. Dehmer GJ, Flrth BG, Lewis SE, Wilierson JT, Hiliis LD. Direct measurement of cardiac output by gated equilibrium blood pool scintigraphy: validation of scintigraphic volume measurements by a nongeometric technique. Am J Cardiol 1981;47:1081-7. 24. Siutsky R, Karllner J, Riccl D, et al. Left ventricular volumes by gated equilibrium radionuclide angiography: a new method. Circulation 1979;60:556-64. 25. Maesle B, Kramer B. Radionuciide determination of left ventricular volume: comparison of counts-based and geometric methods (abstr). Am J Cardiol 1981;47:454. 26. Ong L, Coromilas J, Padmanabhan V, Robblns M, Reiser P, Morrison J. Ventricular volumes by gated equilibrium radionuclide angiography (abstr). Clin Res 1980;28:617A. 27. Links JM, Becker LC, Schlndledecker JG, et al. Determination of absolute left ventricular volume from gated blood pool imaging with an attenuation corrected count rate method (abstr). Am J Cardiol 1980;45:407. 28. Ganz W, Donoso R, Marcus HS, Forrester JS, Swan HJC. A
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29.
30. 31.
32.
a4
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technique for measurement of cardiac output by thermodilution in man. Am J Cardiol 1971;27:392-6. Forrester JS, Ganz W, Diamond G, McHugh T, Choneite DW, Swan HJC. Thermodilution cardiac output determination with a single flowdirected catheter. Am Heart J 1972:83:306-l 1. Gant W, Swan HJC. Measurement of blood flow by thermodilution. Am J Cardiol 1972;20:241-6. Phillips CM, Davlla JC, Sanmarco ME. Measurement of cardiac output by thermal dilution II. A new computer for rapid convenient determinations. Med Res Eng 1970;9:25-9. Holman EL, Wynne J, Zlelonka JS, ldolne JD. A simplified tech-
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nique for measuring right ventricular ejection fraction using the equilibrium radionuclide angiocardiogram and the slant-hole collimator. Radio1 1981;138:429-35. 33. Gorls ML, Daspit SG, McLaughlin P, Krlss JP. Interpolative background subtraction. J Nucl Med 1976;17:744-7 34. Swan HJC. Problems in the measurement of ventricular volumes. UCLA Forum Med Sci 1970;10:185-92. 35. Parker JA, Uren RF, Jones AG, et al. Radionuclide left ventriculogram with the slant hole collimator. J Nucl Med 1977;18:84851.
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