Determination of left ventricular mass by computed tomography

Determination of Left Ventricular Mass by Computed Tomography

CLAES G . SKIOLDEBRAND, MD' MARTIN J . LIPTON, MD, FACCt CONSTANTINE MAVROUDIS, MD THOMAS T . HAYASHI, PhD San Francisco, California

The capability of computed tomographic scanning to provide measurements of left ventricular mass in vivo was explored and compared with postmortem values. The study group comprised 22 dogs weighing between 9 and 28 kg and included 5 dogs with left ventricular hypertrophy . Serial nongated computed tomographic scans from the cardiac apex to base were obtained during steady state Infusion of contrast medium. The total number of picture elements (pixels) representing the left ventricular myocardium on each 1 cm thick computed tomographic scan was determined in two ways : with a computer technique and with a manual tracing method . Left ventricular mass was calculated as the product of total myocardial volume (determined by pixels) and the specific gravity of canine myocardlum . The results obtained with both computed tomographic methods correlated with the left ventricular mass measured at autopsy (computer method, correlation coefficient [r] = 0 .95 ; standard error of the estimate [SEE] = 8 .10 g and for the tracing method, r = 0 .95 ; SEE = 8 .38 g) . These in vivo measurements were reproducible and appeared not to be significantly affected by left ventricular hypertrophy . The effect of cardiac motion on the measurements was assessed by rescanning eight animals at postmortem examination with the heart In situ . These results showed a modest (twofold) Increase due to motion in the standard error of the estimate over the computed tomographic value at autopsy . Artifact due to adjacent lung tissue with low density is known to be a source of error in computed tomographic measurements . This was examined by scanning the excised hearts in a water phantom and was found not to significantly Influence the results . This feasibility study represents a logical step in the application and validation of computed tomography in diagnosing heart disease . The extrapolation of these results to human subjects must be made cautiously, but there appear to be no major technical reasons why this use of computed tomography cannot be optimistically pursued .

From the Department of Radiology and the Cardiovascular Research Institute at the University of California, San Francisco, California, and Department of Mechanical Engineering, University of California, Berkeley, California . Manuscript received April 13, 1981 ; revised manuscript received July 1, 1981, accepted July 15, 1981 . Supported in part by the Sweden-American Foundation, Stockholm, Sweden . 1 Recipient of a Public Health Service Research Career Development Award, Grant 5K04 HL00360, from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland . Address for reprints : Martin J . Lipton, MD, Department of Radiology, S-358, University of California, San Francisco, California 94143 .

Advances in the management and treatment of patients with heart disease have resulted in a wide variety of techniques for evaluating cardiac dimensions and performance . Left ventricular mass is known to change with many acquired and congenital disorders including localized forms of ventricular obstruction, cardiomyopathy and systemic hypertension . There is evidence that measurements of left ventricular mass in obstructive lesions are proportional to the severity of left ventricular overload1-4 and that advanced hypertrophy may be associated with a poor prognosis . 5- s Conversely, detecting the regression of left ventricular hypertrophy after therapeutic interventions may be a critical index of prognosis. Measurements of left ventricular mass may also play an important role together with other variables in providing estimates of myocardial oxygen consumption in patients . Hence, accurate estimates of total left ventricular mass, particularly in serial studies, would be of value in the diagnosis and evaluation of treatment of many heart disorders . Noninvasive methods of obtaining estimates of left ventricular mass include M mode and two dimensional echocardiography . Two di-

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mensional echocardiography was recently reporteds -11 to provide estimates of left ventricular mass that correlated well with autopsy values . Sources of error using this technique include difficulties in precisely identifying the inner and outer boundaries of the left ventricle as well as in interobserver reproducibility . Furthermore, a complete echocardiographic study is not possible in every patient . Cardiac computed tomographic scanning, one of the most recent cardiac imaging techniques, has been shown to provide sharp delineation of cardiac structures despite heart motion . Cardiac dimensions such as ventricular volumes and wall thickness have been successfully determined with computed tomography in excised hearts' 2 and left ventricular silicone casts . 13 In vivo computed tomographic measurements of the interventricular septum have also shown a good correlation with corresponding autopsy measurements . 14 This study was designed to evaluate the accuracy and reproducibility of nongated computed tomographic scanning in measuring left ventricular mass using autopsy weight for validation . The influence of cardiac motion and left ventricular hypertrophy on such measurements was also explored . Methods Experimental preparation: Twenty-two dogs including 10 pedigreed beagles (weighing 9 to 13 kg) and 12 mongrel dogs (weighing 16 to 28 kg) were included in this study . In 5 of the 10 beagles left ventricular hypertrophy was induced at age 6 weeks by a banding operation of the ascending aorta, and computed tomographic studies were performed 7 to 9 months later ; the remaining 5 beagles were litter-matched normotensive control dogs . The 12 mongrel dogs were normal . Daring the computed tomographic study the dogs were anesthetized and intubated with a cuffed endotracheal tube

connected to a dual phase Harvard pump respirator . Ketamine hydrochloride (10 mg/kg body weight) was used for anesthesia in the beagles and sodium pentobarbital (30 mg/kg) in the mongrel dogs . An 18 gauge angiocatheter was placed in a peripheral vein to deliver contrast medium, anesthetic drugs and other pharmacologic agents . The dogs were held supine in a plexiglass cradle, and moved head first into the scanner . Intravenous succinylcholine (1 mg/kg) was given intermittently to paralyze respiration, and 5 to 6 seconds before each computed tomographic scan the respirator was turned off at maximal inspiration in order to keep the diaphragm low and to eliminate motion artifacts from the bony thorax . The electrocardiogram was monitored continuously during the experiments and the heart rate was kept between 60 and 90 beats/min by intramuscular administration of xylazine (0 .5 to 1 .0 mg/kg) . Computed tomographic scanning : The computed tomographic scanner used in this experiment was a modified General Electric whole body scanner, model CT/T 7800, which completes the full 360° scan in 2 .4 seconds . Sequential scanning with approximately 1 second interscan delay time enables up to 12 scans to be exposed in 40 seconds . Initially the level of the cardiac apex and base was determined by obtaining computed radiographs in the anteroposterior and lateral projections (Fig . 1) . All subsequent scans were then indexed with reference to one of these levels . Contrast medium (meglumine sodium diatrizoate [Renografin76®]) was then infused intravenously with a Harvard infusion pump . Typically in the mongrel dogs, a total of 2 ml/kg was infused for 10 minutes and then the infusion rate was decreased to 2 ml/min and maintained at this level during computed tomographic scanning . The beagles received approximately 40 ml of contrast medium during 10 minutes before scanning and then 1 .5 ml/min during the computed tomographic study. Nongated 10 mm thick computed tomographic scans from the cardiac apex to base were obtained . Eight to 12 scans were required for each dog and the scan time was 50 seconds . Two respiratory cycles were allowed between each scan while the scanning table moved at 10 mm incre-

FIGURE 1 . Computerized radiographs (lateral and anteroposterior projections) of a dog's chest obtained with the X-ray tube and the detector array stationary while the scanning table with the dog supine on it is moved through the gantry . The cardiac apex and base were identified (dotted lines) and used as reference levels for the subsequent computed tomographic scans .

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ments . Six dogs subsequently underwent scanning on three different occasions at 2 to 5 day intervals to determine the reproducibility of our computed tomographic results, All dogs finally received an overdose of sodium pentobarbital, Eight dogs underwent repeat scanning in precisely the same supine position immediately after death . The excised hearts of these dogs were then scanned in a plexiglass water phantom to determine the effects of cardiac motion and beam hardening artifact on computed tomographic measurement of left ventricular mass . Computed tomographic analysis : The projection data of a computed tomographic scan are processed by computer to produce an image composed of 320 by 320 picture elements (pixels), where each pixel represents a cross-sectional area of 1 .3 X 1.3 mm . The resulting image is displayed on a black and white video monitor . The brightness of a pixel is directly proportional to the X-ray attenuation coefficient of the tissues . This is expressed in a quantitative manner in terms of Hounsfield computed tomographic units, which are derived from the equation : 1,000 (A-A w ) CT number = Aw where A is the computed attenuation coefficient and A µ, is the attenuation coefficient of water . Consequently, water is calibrated to 0 and air to -1,000 . The video monitor allows a windowed display system in which values of absorption above and below the window range are respectively displayed as black or white, and those within the window width are displayed over a broad gray scale .

The computed tomographic scans were displayed with a magnification factor of 3 . and the total number of pixels representing the left ventricular myocardium was calculated by two methods . A and B . to be described . Because the pixel size is known as well as scan thickness the total volume of left ventricular myocardium can be calculated and left ventricular mass is given by the following equation ; LV (sra,ns) = 1 V,,, X 1 .063,

where V, n is the volume of left ventricular myocardium in cubic centimeters for each scan and n is the number of scans . The value 1 .063 is the specific gravity of canine heart muscle . 15 Both methods used for the computed tomographic analyses depend on identifying the myocardial boundary . Edge detection was accomplished by calculating the computed tomographic number representing a value halfway between the mean computed tomographic number of the adjacent structures defining these boundaries, namely, ventricular cavity and lung (Fig . 2) . A range of computed tomographic numbers was thereby obtained that represented the computed tomographic number of myocardium . In method A the cursor is positioned within the myocardium and the computer is instructed to select all those con-

tiguous pixels that have computed tomographic values lying within the chosen range defined by the operator. To ensure that the computer did not include the right ventricular wall the operator excluded it by tracing cutoff lines (Fig . 3, top) . Method B requires the operator to trace the inner and outer borders of the left ventricular myocardium with a track ball cursor . This procedure is facilitated by having those pixels

defining the myocardial edge intensified in brightness on the video monitor . The computer determines the number of pixels within the defined region (Fig . 3, bottom) and calculates their total area . These methods were repeated three times for each slice by two independent observers to determine the precision and reproducibility of these techniques . Postmortem analysis : Anatomic left ventricular mass was determined at autopsy in fresh specimens after removal of the free right ventricular wall, atria and the aortic and mitral valves. Epicardial fat surrounding the coronary arteries was also carefully excised . The unfixed left ventricle, defined as the free left ventricular wall and the interventricular septum, was washed in saline solution, blotted dry and weighed to the nearest gram . Each left ventricular specimen was reweighed four times to determine the reproducibility of autopsy weight, and the average was taken as the true weight . Statistical analysis: The computed tomographic estimates of left ventricular mass were compared with the anatomic weights by simple linear regression analysis, and the standard error of the estimate was calculated . Reproducibility of the in vivo computed tomographic studies as well as inter- and intraobserver variability were determined by a simple analysis of variance . Results

Computed tomographic scan obtained 30 mm from the cardiac apex during infusion of contrast medium . Rectangular areas of interest have been selected over various tissues . The mean computed tomographic numbers of the left ventricular myocardium, left ventricular cavity and surrounding lungs were then calculated by pixel analysis . The computer calculates the computed tomographic number and standard deviation of all the pixels within each defined area of interest . The inner and outer boundaries of the left ventricular myocardium were defined as the value between the mean computed tomographic number of left ventricular myocardium and adjacent tissue . This method defines the myocardial boundaries . FIGURE 2.

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Image quality : With use of contrast medium enhancement, the cardiac chambers, myocardium and structures such as papillary muscles and trabeculae were readily identified at appropriate scan levels (Fig. 4) . Concentric left ventricular hypertrophy could also be recognized (Fig . 5) . Accuracy of in vivo left ventricular mass estimates by computed tomography : The standard for comparison of left ventricular mass estimated with computed tomographic methods was the autopsy weight

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determination . The variability in measurements (four times for each left ventricle) was less than ±0 .25 g . Both methods used for analyzing the computed tomographic scans obtained in vivo correlated well with the autopsy findings: For the computer method, correlation coefficient [ri = 0.95, standard error of the estimate (SEE) = 8.1 g (Fig . 6, left), and for the tracing method, r = 0 .95 and SEE = 8.4 g (Fig. 6, right) .

Reproducibility: The variability of estimation of left ventricular mass by computed tomography, assessed in six dogs subjected to scanning on three successive occasions over I week, was found to be ±5 .2 g . Intraobserver variability, as measured by standard deviation, was found to be ±3 .8 g. Two independent observers showed an average variability of 5 .6 g between average measurements for these six dogs . (r value 0 .89) . Measurement of left ventricular mass after death showed a 56 percent decrease in the standard error of the estimate compared with that of in vivo estimates . Discussion

FIGURE 3. Two methods of computed tomographic analysis are illustrated . The top panel illustrates the computer method . Cutoff lines are traced at locations where the left ventricular myocardium is directly adjacent to other structures that have a computed tomographic number similar to that of left ventricular myocardium . The bottom panel shows the same scan analyzed by the manual tracing technique . The area of the left ventricular myocardium assessed by either of these two methods (depicted in the lower rlrjn carer as square centimeters in both panels) multiplied by the scan thickness (10 mm) gives the volume of left ventricular myocardium for each scan .

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Since the introduction of computed tomography in 1972, this new X-ray technique not only has been shown to yield useful clinical information, but also has replaced many angiographic procedures in the brain . The heart is a particularly challenging organ because of its continuous motion. Previous in vitro computed tomographic studies in arrested hearts indicated the potential for dimensional measurementsl 2,16 and myocardial infarct detection and sizing . 17-20 In vivo application of cardiac computed tomography using contrast medium enhancement has shown increasing promise for both clinical and research purposes . 14,21 .22 The application of computed tomography for cardiac dimensional measurements in the clinical setting requires experimental in vivo validation . The major purpose of this study was to compare computed tomographic estimates of left ventricular mass in vivo with those obtained at autopsy. Additionally, we directly compared the results of computed tomographic measurements in vivo with those made of the same hearts in vitro, when ideal scanning conditions are possible . Our findings demonstrate that in vivo nongated scanning can give reproducible and accurate measurements of left ventricular mass . A reproducibility value of ±5 .2 g for left ventricular mass in the same animal at different times is remarkably good in light of both the present limitations of computed tomographic scan time and cardiac motion . It should be noted that two dimensional echocardiography and biplane angiography have not documented this degree of accuracy, namely 5 percent of left ventricular mass . Potential errors in measurements: Because the computed tomographic image is derived from X-ray attenuation coefficients of various structures, boundary detection might be expected to be difficult . Our study examined the effect of cardiac motion as well as errors caused by surrounding lung and soft tissues by scanning the arrested hearts in situ and additionally in a water phantom . Our results indicate that only a modest twofold increase in the standard error of the computed tomographic estimates can be expected when studies performed in vivo are compared with computed tomographic studies performed in situ, after cardiac arrest . Computer versus manual training method : The two methods described for analyzing the computed tomographic data are available on the computed tomographic scanner display console, and both provide ac-

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FIGURE 4. Serial contiguous 10 mm thick com-

puted tomographic scans from apex (S 3) to base (S 11) in a beagle with sytImetrical left ventricular hypertrophy, obtained during steady state infusion of contrast medium. The ascending aorta (AA), descending aorta (AO), inferior vena cave (IVC), posterior papillary muscle (PPM), anterior papillary muscle (APM), left ventricle (LV) and right ventricle (RV) are identified at appropriate scan levels,

curate measurements of left ventricular mass . The computer method, which may seem more appealing than the manual tracing method, was actually more complicated and time-consuming . Not only must several structures be eliminated by tracing cutoff lines (Fig . 3, top) but the technique may also be influenced by streak artifacts that sometimes occur over the myocardium and can result in significant errors . The logical next step will be to evaluate the method in patients . The total dose of contrast medium ad-

ministered to the animals was large in order to compensate for cardiac motion and to obtain optimal scanning conditions . We have subsequently obtained adequate density resolution using smaller doses of contrast medium . However, with use of present instruments, in a 70 kg patient 150 to 250 ml of contrast agent will be required to identify the myocardial wall adequately . Cardiac computed tomographic scanners capable of subsecond or millisecond exposure times and multislice capability are being developed . 23 These in-

FIGURE 5. Scans through the mid portion of the

heart in two dogs . The scan in the right panel (BANDED) was obtained from a hypertensive dog 9 months after aortic banding with consequent left ventricular hypertrophy . The left panel (CONTROL) is a similar scan from a normotensive littermatched control dog . Note the hypertrophied interventricular septum and marked symmetrically thickened left ventricular free wall in the hypertensive dog.

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VENTR'G.i'_AR VASS 9V OOVRU- -p.ynrgA`Y_SY~C` .,-oAVD _- A'_

MEASUREMENT OF LV MASS BY C1 (Computer Method)

MEASUREMENT OF LV MASS BY CT (Manual Tracing Method)

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FIGURE 6 . Relation between autopsy values and computed tomographic (CT) estimates of left ventricular (LV) mass by two different computed tomographic methods . Left, results for the computer method . Filled triangles represent normotensive dogs ; open triangles represent the beagles with left ventricular hypertrophy. The lines on either side of the regression line indicate the 95 percent confidence limits . Right, results for the manual method . Both methods show a similar close relation between computed tomographic and anatomic estimates of left ventricular mass .

struments will require far less contrast medium because cardiac motion artifacts will not present the significant problem they do in current computed tomographic body scanners . Comparison with left ventricular angiography : Computed tomography provides tomographic and potentially three dimensional imaging and therefore avoids some problems and errors that occur with angiographic as well as echocardiographic estimations . The latter methods require assumptions based on ventricular geometry and uniformity of left ventricular wall thickness . Uniform geometry and thickness do not occur in many patients with ischemic and myopathic disease ; hence, the techniques must have fundamental inaccuracies in the patients for whom these measurements are most needed. Left ventriculography has been used for measuring left ventricular mass . 24,25 This procedure is not performed routinely, mainly because it is tedious and unreliable . Wall thickness can be measured only over a relatively small area near the cardiac apex and the ventricular wall must be assumed to be uniform, which is usually not the case . Furthermore, the angiographic method is not applicable in patients with right ventricular hypertrophy, pericardial thickening or effusion or pleural thickening . Computed tomography has the potential to measure left ventricular mass even when these complicating conditions are present . The accuracy of biplane angiography for determining left ventricular mass using the anteroposterior and lateral projections was studied in 1964 by Rackley et al . 24 in an autopsy series of 23 human hearts . This method is dependent on calculating chamber volume and chamber volume plus ventricular wall thickness ;

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hence, corrections were made for magnification . Wall thickness could be seen and measured only at limited sites, and volumes were calculated assuming the chamber to be an ellipsoid . The results gave a percent standard deviation of regression line of 10 to 20 percent depending on heart size and weight . Kennedy et al . 25 in 1967 compared biplane angiographic measurements of left ventricular mass in 28 patients with the corresponding autopsy weights . The percent standard deviation of regression line was similar to that in the study of Rackley et al ., 10 to 20 percent. Single plane angiography was also examined for this purpose by Kennedy et al. 26 in 1970. A comparison of anteroposterior and right anterior oblique single plane methods showed that the anteroposterior plane is satisfactory for normal hearts but, when hypertrophy is present, the right anterior oblique projection is necessary to see the ventricular wall . The results cannot be expressed in absolute terms ; hence, no percent of standard deviation can be given, because this study compared biplane with single plane methods . However, the error for the anteroposterior view was large, ±53 g, and for the right anterior oblique view was ±42 g compared with 23 g for the biplane angiographic results . Comparison with echocardiographic methods : M mode echocardiography has been used to measure wall thickness and left ventricular mass but this technique has fundamental limitations . 27,28 Two dimensional echocardiography has also been explored for this purpose in our own laboratory 10 and elsewhere, and results of left ventricular mass measurements in dogs using this technique have correlated well with those obtained at autopsy . 9-11 Unlike M mode echocardiog-

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raphy this technique more accurately defines the long and short axis of the left ventricle . Additionally, cross sections of the heart can be obtained at more than one level ; this method therefore has the potential for evaluating changes in left ventricular wall thickness . However, there are major difficulties associated with two dimensional echocardiography . Salcedo et al ." compared M mode and two dimensional echocardiography in living dogs in a well designed study for measuring left ventricular mass and used autopsy weight for validation. M mode echocardiography grossly overestimated left ventricular mass ; the standard deviation of the regression line was 54 percent . The correction of Teichholz et al . 29 reduced this overestimation, but it was still 28 percent (r = 0.646) . Two dimensional studies were performed in 19 dogs and left ventricular mass was calculated based on the formula described by Troy et al.27 using three different methods . The long axis was determined by two dimensional echocardiography ; D 2 was the transverse short axis and the mean wall thickness (WT) was the average wall thickness taken from five different sites . The accuracy of these three options is best appreciated when expressed in terms of percent standard deviation of regression line : for LD2 (where D 2 = anterior/posterior axis) it was 56 percent ; for LD,D 2 (where D2 = transverse axis) it was 23 percent ; and using wall thickness LD,D2 WT it was 14 percent . The corresponding accuracy of the computed tomographic method described in our present study was less than 10 percent . Computed tomographic values are therefore at least as good as the best two dimensional echocardiographic estimates after considerable data manipulation .' 1 Computed tomography has the added advantage of providing direct measurements of myocardial mass . Image boundary definition by echocardiography is observer-dependent and in a significant proportion of patients a complete technical study cannot be ob-

tained by echocardiography . In contrast, computed tomography methods provide computer-assisted edge detection, and emphysema does not impair the technical quality of computed tomography images . The obvious advantage of echocardiography is that no contrast agent need be administered . However, the data provided are limited because wall thickness can be measured only in specific regions, optimally the septum and posterior wall. Some geometric assumptions must also be made to deduce left ventricular mass because two dimensional echocardiography in its present form is not a truly three dimensional imaging technique. Finally, the potential for error is greatest with asymmetric hypertrophy or abnormal chamber configurations, or both-situations that are frequently encountered in clinical practice . Implications: Our study indicates the capability of computed tomography to provide accurate dimensional measurements even without electrocardiographic gating . However, the extrapolation of the results of this experimental study to patients must be guarded . Nevertheless feasibility studies such as the present one are logical necessary steps for the ultimate development and application of computed tomography in the diagnosis of heart disease .

Acknowledgment We are grateful to Lauranne Cox, RT, Anthony Brito, RT and James Stoughton, RT for technical assistance . We also thank Julien I . E . Hoffman, MD, Professor of Pediatrics, University of California, San Francisco for his advice and criticism of this work . Walter H . Berninger, PhD and Rowland Redington, PhD, of the General Electric Research and Development Center, Schenectady, New York are thanked for the hardware and software modifications of the computed tomographic scanner . We are also indebted to Douglas P . Boyd, PhD, Professor of Physics, Department of Radiology at the University of California for expert advice regarding the collection and analyses of computed tomographic data .

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Skidldebrand CG, Ovenfors CO, Mavroudis C, Lipton MJ . Assessment of ventricular wall thickness in vivo by computed transmission tom graphy . Circulation 1980 ;61 :960-5, Ylplntsol Y, Scanlon PD, Bassingthwalghte JB . Density and water content of dog ventricular myocardium . Proc Soc Exp Biol Med 1972 ;41 :1032-5 .

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16 . Guthaner OF, Wexler L, Harell G . CT demonstration of cardiac structures . AJR 1979 ;133 :75-81 . 17 . Adams OF, Hessel Si, Judy PF, Stein JA, Abrams HL Computed tomography of the normal and infarcted myocardium . AJR 1976 :126;786-91 . 18 . Powell WJ Jr, Wittenberg J, Maturl RA . Detection of edema associated with myocardial ischemia by computerized tomography in isolated arrested canine hearts . Circulation 1977 ;55 :99-108 . 19 . Higgins CB, Siemers PT, Schmidt W, Newell JD . Evaluation of myocardial ischemic damage of various age by computerized transmission tomography . Time dependent effects of contrast material . Circulation 1979 ;60 :284-91 . 20 . Doherty PW, Lipton MJ, Berninger WH, Skioldebrand CG, Carlsson E, Redlngton RW . The detection and quantitation of myocardial infarction in vivo using transmission computed tomography . Circulation 198 1 ;63:597-606 . 21 . Lipton MJ, Brundage Bill, Doherty PW, et at . Contrast mediumenhanced computed tomography for evaluating ischemic heart disease. Cardiovasc Med 1979 ;4 :1219-29 . 22 . Lipton MJ, Higgins CB . Evaluation of ischemic heart disease by computerized transmission tomography . Radio) Clin North Am 1980;18 :557-7623 . Boyd DP, Gould RG, Quinn JR, Sparks R, Stanley JH, Herm-

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annfeldt WB . A proposed dynamic cardiac 3-D densitometer for early detection and evaluation of heart disease . IEEE Trans Nucl Sci 1979 ;NS-26 :272-7 . 24 . Rackley CE, Dodge HT, Coble YD, Hay RE . A method for determining left ventricular mass in man. Circulation 1964 ;24:66671 . 25. Kennedy JW, Reichenbach OD, Bacley WA, Dodge HT . Left ventricular mass: a comparison of anglocardiographlc measurements with autopsy weight . Am J Cardiol 1967 ;19 :221-3 . 26 . Kennedy JW, Trenholme SE, Kasser IS . Left ventricular volume and mass from single-plane cineangiocardiogram . A comparison of anteroposterior and right anterior oblique methods . Am Heart J 1970;80 ;343-52 . 27 . Troy BL, Pombo J, Rackley CE . Measurements of left ventricular wall thickness and mass by echocardiography . Circulation 1972 ;45:602-11 . 28 . Devereux RB, Relchek N, Klunder PJ . Echocardiographic determination of left ventricular mass in man . Anatomic validation of the method . Circulation 1977;55 ;613-8 . 29 . Telchholz LE, Kreulen T, Herman AV, Goriin R . Problems in echocardiographic volume determinations : echocardiographicangiographic correlations in the presence or absence of asynergy . Am J Cardiol 1976;37 :7-11 .

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