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Ultrasonic tissue characterization: Prospects for clinical cardiology
JACC Vol. 14, No. 7 December 1989: 1709-I
1709
I
Editorial Comment
Ultrasonic Tissue Characterization: Prospects for Clinical Cardiology* SAMUEL
A. WICKLINE,
BURTON
E. SOBEL,
MD, FACC,
MD, FACC
St. Louis. Missouri
The hypothesis that ultrasonic interrogation of myocardial tissue can yield information characterizing intrinsic structural properties with specific histopathologic correlates in the heart was explored as long as 30 years ago when Wild et al. (1) applied ultrasonic tissue characterization in vitro to excised human hearts harboring infarcts. Recent reports (2-16) from our laboratory and others have demonstrated the applicability of this approach in vivo, first in experimental animals (2-12) and subsequently in human subjects (13-16). The potential value of the approach and its complementarity to conventional two-dimensional and Doppler imaging are underscored by the impressive results by Masuyama et al. (17) reported in this issue of the Journal. These workers have used a prototype of a commercial instrument developed initially through a collaboration between the HewlettPackard Company and Washington University in St. Louis (18). Objectives of backscatter imaging: Ultrasonic characterization of myocardium with integrated backscatter is designed to provide a robust measurement of the structural and functional properties of heart muscle by directly quantifying tissue acoustic properties through analysis of unprocessed radiofrequency data (19). The approach complements and is distinct from analysis of wall motion and chamber dimensions. The magnitude of ultrasonic backscatter from cardiac tissue depends on fundamental physical properties such as local elasticity, density and fiber geometry (shape, size, concentration and orientation of scattering elements). Alter-
*Editorials published in Journal of the American College of Cardiology
reflect the views of the authors and do not necessarily represent the views of JACC or the ,4merican College of Cardiology. From the Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri. Work from the authors’ laboratory was supported in part by Grants HL-17646 (SCOR in Ischemic Heart Disease) and
HL-42950from the National Institutes of Health, Bethesda. Maryland, and a Clinician-Scientist Award from the American Heart Association (Dr. Wickline). Address for reorints: Burton E. Sobel, MD, Cardiovascular Division, Washington University School of Medicine. 660 South Euclid Avenue, Box 8086, St. Louis, Missouri 63110. 01989 by the American College of Cardiology
ations of these properties associated with myocardial infarction and cardiomyopathy (edema, fibrosis and calcification) have been delineated sensitively with quantitative backscatter in studies of experimental animals and human subjects (19). Until recently, ultrasonic tissue characterization has been explored primarily in laboratory studies of ischemia, infarction and cardiomyopathy. However, with the development of a prototype real-time backscatter imaging system by modification of a commercially available two-dimensional echocardiographic imager (18), broader clinical investigation became feasible. This important step in the maturation of backscatter imaging follows more than 10 years of extensive laboratory research (2-16). The prototype backscatter imaging system used by Masuyama et al. (17) of Stanford and previously by others (14-16,20) permits measurement of the cardiac cycledependent variation of integrated backscatter. However, such information is but a subset of the total information potentially obtainable by tissue characterization (19). Cyclic variation of backscatter was reported initially by Madaras et al. (21) in studies of open chest dogs interrogated with a broadband insonifying transducer placed in direct contact with the beating heart. Spectral analysis of the radiofrequency data at selected intervals throughout the cardiac cycle indicated that over the range of frequencies measured, the average amplitude of ultrasound backscattered from the tissue was greater at end-diastole than at end-systole in hearts with normal contractile function. The observation that cyclic alterations in the physical properties of heart muscle were apparent by measurement of changes in tissue acoustic properties that resulted from contraction and relaxation of myofibrils suggested that tissue characterization might provide a useful dynamic index of regional and intramural contractile properties. Results <$ subsequent studies in experimental animals have supported the hypothesis that cyclic variation is a useful measure ofregional contractile properties. The mag-
nitude and rate of change of backscatter parallel alterations of ventricular contractile performance induced by propran0101(decreased) and paired pacing (increased) and reflected by changes in maximal rate of rise of left ventricular pressure (dP/dt,,,) (22,23). Furthermore, subendocardial regions manifest greater amplitudes and rates of change of cyclic variation than do subepicardial regions in accordance with the recognized greater contribution of subendocardial zones to overall wall thickening. A recent report (24) indicates that cyclic variation decreases substantially immediately after the onset of ischemia in dogs but recovers more rapidly than regional wall thickening after reperfusion in reversibly injured or “stunned” myocardium. Similar findings have been 0735%1097/89/$3.50
1710
WICKLINE AND SOBEL EDITORIAL COMMENT
reported in studies of patients with stunned myocardium after recanalization of coronary arteries induced with recombinant tissue-type plasminogen activator (t-t-PA) (16). Recovery of cyclic variation of backscatter appears to precede recovery of regional wall thickening in myocardium supplied by a transiently occluded artery (16). Accordingly, tissue characterization may be particularly useful in the longitudinal assessment of recovery of contractile function after recanalization induced by thrombolysis, angioplasty or other interventions. The impact of findings by Masuyama et al. (17): These authors report their experience with integrated backscatter imaging in patients with normal cardiac structure and function adjudged on the basis of clinical criteria. Their report is particularly interesting because it confirms that backscatter imaging can be accomplished with reasonable accuracy in a diverse group of subjects of diverse age. Inter- and intraobserver variability approximates that reported previously by Vered et al. (14,15) in studies of normal volunteers. Thus, results of clinical investigation with ultrasonic tissue characterization are likely to be reproducible and consistent among different groups of investigators who use comparable imaging protocols. The observation by Masuyama et al. (17) that cyclic variation declines with advancing age is intriguing. It may
seem surprising at first blush because cyclic variation depends in part on contractile performance, which is generally thought to be well preserved in the absence of disease despite advanced age. However, the hearts of elderly subjects may harbor degenerative changes manifested by or associated with hypertrophy, diastolic dysfunction and “senile amyloidosis,” which may exert subtle influences on systolic contractile performance. Myocardial tissue stiffens with age because of accumulation of collagen (25). In addition, the absolute magnitude of backscatter is determined in part by the collagen content of tissues (4,5,26). Thus, tissue characterization may evolve as a powerful tool for detecting and quantifying structural changes such as collagen deposition accompanying aging, some of which may be responsible for currently only poorly understood functional abnormalities. Masuyama et al. (17) observed a pattern of regional differences in cyclic variation of backscatter characterized by significantly greater cyclic variation in the posterior wall as compared with that in the septum, consistent with results of other reports (14,15,20). Similar regional differences in the magnitude of cyclic variation have been observed from apex to base and intramurally (12,22,27). Such differences appear to parallel regional differences in contractile performance. However, it is not possible to exclude some dependence of the magnitude of cyclic variation observed on the echocardiographic view chosen for imaging (20). The magnitude of both ultrasonic backscatter and attenuation is known to depend in part on the angle of insonification of aligned
JACC Vol. 14, No. 7 December 1989: 1709-l 1
scatterers such as heart fibers that can intluence the magnitude of cyclic variation and may require normalization according to the predominant fiber angle expected with a given view (28-30). View-dependent attenuation of ultrasound as it propagates through the chest may be important as well (31,32). Masuyama et al. (17) report that the “delay” associated with cyclic variation is relatively constant throughout the different myocardial regions characterized and in the different age groups studied. The value for delay (originally called “phase” in references 11 and 33) represents the temporal extent of synchrony of regional and global contractile events (its use as a parameter of regional contractile synchrony is similar conceptually to the use of parameters in two-dimensional phase images acquired from radionuclide ventriculograms subjected to Fourier analysis). Recent results (24) indicate that prolonged delay of cyclic variation is a marker of acute ischemic injury. However, the recovery of delay is typically more rapid than recovery of wall thickening with reperfusion after transient coronary occlusion. Thus, it may provide an early index of viability of stunned myocardium before recovery of mechanical function. The report by Masuyama et al. (17) demonstrates that the value calculated for delay may be relatively insensitive to the particular myocardial region selected for study and may therefore provide a robust measurement of regional contractile properties relatively independent of echocardiographic view. Masuyama et al. (17) emphasize the present lack of a standard approach for analysis of cyclic variation. Various
methods have been used to determine the peak to peak magnitude and the delay of cyclic variation, including Fourier analysis of the fundamental harmonic and manual methods that locate peaks and nadirs of the backscatter curve with respect to electrocardiographic fiducial points. Standardization of analytic methods is critical for acquisition of results that can be compared directly among different groups of investigators. Recently, our group (33,34) described one promising method for determination of the magnitude and cyclic variation that uses a cross-correlation algorithm to fit a model function to the observed data. Implications. Results of the meticulous study by Masuyama et al. (17) underscore the potential clinical utility of ultrasonic tissue characterization of the heart. Judging from the extensive information acquired in many laboratories over the past decade, several clinical conundrums may be resolvable with the help of backscatter imaging implemented to characterize fundamental physical properties of the heart such as microscopic variation in elasticity and density, and three-dimensional microstructural organization. Widespread clinical utilization of this promising approach will undoubtedly stimulate refinement and provide the experience necessary to maximize its diagnostic and prognostic power.
WICKLINE AND SOBEL EDITORIAL COMMENT
JACC Vol. 14, No. 7 December 1989:1709-l i
References I. Wild JJ, Crafford HD, Reid JM. Visualization of the excised human heart by means of reflected ultrasound or echography. Am Heart J 1957; 54:903-6. 2. Mimbs JW. Yuhas DE, Miller JG, Weiss AN, Sobel BE. Detection of myocardial infarction in vitro based on altered attenuation of ultrasound. Circ Res l977:41:192-8. 3. Mimbs JW. O’Donnell M, Miller JG, Sobel BE. Changes in ultrasonic attenuation indicative of early myocardial ischemic injury. Am J Physiol 1979:236:H34&4. 4. O’Donnell M. Mimbs JW. Miller JG. Relationship between collagen and ultrasonic backscatter in myocardial tissue. J Acoust Sot Am 1981: 69:580-8. 5. Mimbs JW, O’Donnell M. Bauwens D, Miller JW, Sobel BE. The dependence of ultrasonic attenuation and backscatter on collagen content in dog and rabbit hearts. Circ Res 1980;47:48-58. 6. Lele PP, Namery, J. A computer-based system for the detection and mapping of myocardial infarcts. Proc San Diego Biomed Symp 1974; 13:121-32. 7. Skorton DJ, Melton HE III. Pandian NB, et al. Detection of acute myocardial infarction in closed-chest dogs by analysis of regional twodimensional echocardiographic gray level distributions. Circ Res 1983: 5213644. 8. Skorton DJ, Collins SM, Nichols J, Pandian NB, Bean JA. Kerber RE. Quantitative texture analysis in two-dimensional echocardiography: application to the diagnosis of experimental myocardial contusion. Circulation 1983:68:217-23 9. Rasmussen S, Lovelace DE, Knoebel SB. Ransburg R, Corya BC. Echocardiographic detection of ischemic and infarcted myocardium. J Am Coll Cardiol 1984;3:733-43. IO. Schnittger IA, Viele A. Heiserman JE. et al. Ultrasonic tissue characterization: detection of acute myocardial ischemia in dogs. Circulation 1985;72:193-9. Il. Fitzgerald PJ, McDaniel MD, Rolett EL, Strohben JW. James DH. Two-dimensional ultrasonic tissue characterization: backscatter power. endocardial motion and their phase relationship for normal. ischemic. and infarcted myocardium. Circulation 1987;76:85C-9. 12. Sagar KB, Rhyne TL, Warltier DC, Pelt L, Wann S. Intramyocardial variability in integrated backscatter: effects of coronary occlusion and reperfusion. Circulation 1987;75:436-42. 13. Olshansky B, Collins SM, Skorton DJ, Prasad NV. Variation of left ventricular myocardial gray level on two-dimensional echocardiograms as a result of cardiac contraction. Circulation 1984;70:97?-7. 14. Vered Z. Barzilai B. Mohr GA. et al. Quantitative ultrasonic tissue characterization with real-time integrated backscatter imaging in normal human subjects and in patients with dilated cardiomyopathy. Circulation 1987;76:1067-73. 15. Vered Z, Mohr GA, Gessler CJ, et al. Ultrasound integrated backscatter tissue characterization of remote myocardial infarction in human subjects J Am Coll Cardiol 1989;13:84-91. 16. Milunski MR, Mohr GA, Gessler CJ, et al. Ultrasonic tissue characterization with integrated backscatter: acute myocardial ischemia. reperfusion, and stunned myocardium in patients. Circulation 1989;80:491-503. 17. Masuyama T. Nellessen IJ, Schnittger 1, Tye TL, Haskell WL, Popp RL. Ultrasonic tissue characterization with a real time integrated backscatter
1711
imaging system in normal and aging human hearts. J Am Coll Cardiol 1989:14:1702-8. 18. Thomas LJ 111.Barzilai B, Perez JE, Sobel BE, Wickline SA, Miller JG. Quantitative real-time imaging of myocardium based on ultrasonic integrated backscatter. IEEE Trans Ultrason Ferroelectr Frequency Control 1989:36:46670. 19. Miller JG. Perez JE, Sobel BE. Ultrasonic characterization of myocardium. Prog Cardiovasc Dis 1985;28:85-IIO. 20. Vandenberg BF. Rath L, Shoup TA. Kerber RE, Collins SM, Skorton DJ. Cyclic variation of ultrasound backscatter in normal myocardium is view dependent: clinical studies using a real-time backscatter imaging system (abstr). J Am Coll Cardiol 3989:13:226A. 21. Madams El. Barzilai B, Perez JE, Sobel BE. Miller JG. Changes in myocardial backscatter throughout the cardiac cycle. Ultrason Imaging 1983:5:229-39. 22. Wickline SA. Thomas LJ III, Miller JG, Perez JE. The dependence of myocardial ultrasonic integrated backscatter on contractile performance. Circulation 1985:72:183-92. 23. Sagar KB, Pelt LE, Rhyne TL, Wann S. Warltier DC. Influence of heart rate. preload, afterload, and inotropic state on myocardial ultrasonic backscatter. Circulation 1988;77:478-83. 24. Milunski MR, Mohr GA. Wear KA, Sobel BE, Miller JG. Wickline SA. Early identification with ultrasonic integrated backscatter of viable but stunned myocardium in dogs. J Am Coll Cardiol 1989:14:462-71. 25. Weber KT. Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol 1989;13:1637-52. 26. Hoyt RM. Skorton DJ. Collins SM, Melton HE. Ultrasonic backscatter and collagen in normal ventricular myocardium. Circulation 1984: 69:775-82. 27. Mottley JG, Glueck RM. Perez JE, Sobel BE, Miller JG. Regional differences in the cyclic variation of myocardial backscatter that parallel regional differences in contractile performance. J Acoust Sot Am 1984: 76:1617-23. 28. Aygen M, Popp RL. Influence of the orientation of myocardial fibers of echocardiographic images. Am J Cardiol 1957;60:147-52. 29. Mottley JG. Miller JG. Anisotropy of the ultrasonic backscatter of myocardial tissue. 1. Theory and measurement in do. J Acoust Sot Am 1988:83:7Sdl. 30. Madaras El. Perez JE, Sobel BE, Mottley JG, Miller JG. Anisotropy of the ultrasonic backscatter of myocardial tissue. II. Measurements in vim. J Acoust Sot Am 1988;83:762-9. 31. Cohen RD. Mottley JG, Miller JG, Kurnik PB. Sobel BE. Detection of ischemic myocardium in viva through the chest wall by quantitative ultrasonic tissue characterization. Am J Cardiol 1982;50:838-43. 32. Melton HE Jr, Skorton DJ. Rational gain compensation for attenuation in cardiac ultrasonography. Ultrason Imaging 1983;5:214-28. 33. Wickline SA, Thomas LJ III, Miller JG, Sobel BE, Perez JE. Sensitive detection of the effects of reperfusion on myocardium by ultrasonic tissue characterization with integrated backscatter. Circulation 1986; 74:389-400. 34. Mohr GA, Vered Z, Barzilai B, Perez JE. Sobel BE. Miller JG. Automated determination of the magnitude and time delay (“phase”) of the cyclic variation of ultrasonic backscatter from myocardium. Ultrason Imaging 1989(in press).
1709
I
Editorial Comment
Ultrasonic Tissue Characterization: Prospects for Clinical Cardiology* SAMUEL
A. WICKLINE,
BURTON
E. SOBEL,
MD, FACC,
MD, FACC
St. Louis. Missouri
The hypothesis that ultrasonic interrogation of myocardial tissue can yield information characterizing intrinsic structural properties with specific histopathologic correlates in the heart was explored as long as 30 years ago when Wild et al. (1) applied ultrasonic tissue characterization in vitro to excised human hearts harboring infarcts. Recent reports (2-16) from our laboratory and others have demonstrated the applicability of this approach in vivo, first in experimental animals (2-12) and subsequently in human subjects (13-16). The potential value of the approach and its complementarity to conventional two-dimensional and Doppler imaging are underscored by the impressive results by Masuyama et al. (17) reported in this issue of the Journal. These workers have used a prototype of a commercial instrument developed initially through a collaboration between the HewlettPackard Company and Washington University in St. Louis (18). Objectives of backscatter imaging: Ultrasonic characterization of myocardium with integrated backscatter is designed to provide a robust measurement of the structural and functional properties of heart muscle by directly quantifying tissue acoustic properties through analysis of unprocessed radiofrequency data (19). The approach complements and is distinct from analysis of wall motion and chamber dimensions. The magnitude of ultrasonic backscatter from cardiac tissue depends on fundamental physical properties such as local elasticity, density and fiber geometry (shape, size, concentration and orientation of scattering elements). Alter-
*Editorials published in Journal of the American College of Cardiology
reflect the views of the authors and do not necessarily represent the views of JACC or the ,4merican College of Cardiology. From the Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri. Work from the authors’ laboratory was supported in part by Grants HL-17646 (SCOR in Ischemic Heart Disease) and
HL-42950from the National Institutes of Health, Bethesda. Maryland, and a Clinician-Scientist Award from the American Heart Association (Dr. Wickline). Address for reorints: Burton E. Sobel, MD, Cardiovascular Division, Washington University School of Medicine. 660 South Euclid Avenue, Box 8086, St. Louis, Missouri 63110. 01989 by the American College of Cardiology
ations of these properties associated with myocardial infarction and cardiomyopathy (edema, fibrosis and calcification) have been delineated sensitively with quantitative backscatter in studies of experimental animals and human subjects (19). Until recently, ultrasonic tissue characterization has been explored primarily in laboratory studies of ischemia, infarction and cardiomyopathy. However, with the development of a prototype real-time backscatter imaging system by modification of a commercially available two-dimensional echocardiographic imager (18), broader clinical investigation became feasible. This important step in the maturation of backscatter imaging follows more than 10 years of extensive laboratory research (2-16). The prototype backscatter imaging system used by Masuyama et al. (17) of Stanford and previously by others (14-16,20) permits measurement of the cardiac cycledependent variation of integrated backscatter. However, such information is but a subset of the total information potentially obtainable by tissue characterization (19). Cyclic variation of backscatter was reported initially by Madaras et al. (21) in studies of open chest dogs interrogated with a broadband insonifying transducer placed in direct contact with the beating heart. Spectral analysis of the radiofrequency data at selected intervals throughout the cardiac cycle indicated that over the range of frequencies measured, the average amplitude of ultrasound backscattered from the tissue was greater at end-diastole than at end-systole in hearts with normal contractile function. The observation that cyclic alterations in the physical properties of heart muscle were apparent by measurement of changes in tissue acoustic properties that resulted from contraction and relaxation of myofibrils suggested that tissue characterization might provide a useful dynamic index of regional and intramural contractile properties. Results <$ subsequent studies in experimental animals have supported the hypothesis that cyclic variation is a useful measure ofregional contractile properties. The mag-
nitude and rate of change of backscatter parallel alterations of ventricular contractile performance induced by propran0101(decreased) and paired pacing (increased) and reflected by changes in maximal rate of rise of left ventricular pressure (dP/dt,,,) (22,23). Furthermore, subendocardial regions manifest greater amplitudes and rates of change of cyclic variation than do subepicardial regions in accordance with the recognized greater contribution of subendocardial zones to overall wall thickening. A recent report (24) indicates that cyclic variation decreases substantially immediately after the onset of ischemia in dogs but recovers more rapidly than regional wall thickening after reperfusion in reversibly injured or “stunned” myocardium. Similar findings have been 0735%1097/89/$3.50
1710
WICKLINE AND SOBEL EDITORIAL COMMENT
reported in studies of patients with stunned myocardium after recanalization of coronary arteries induced with recombinant tissue-type plasminogen activator (t-t-PA) (16). Recovery of cyclic variation of backscatter appears to precede recovery of regional wall thickening in myocardium supplied by a transiently occluded artery (16). Accordingly, tissue characterization may be particularly useful in the longitudinal assessment of recovery of contractile function after recanalization induced by thrombolysis, angioplasty or other interventions. The impact of findings by Masuyama et al. (17): These authors report their experience with integrated backscatter imaging in patients with normal cardiac structure and function adjudged on the basis of clinical criteria. Their report is particularly interesting because it confirms that backscatter imaging can be accomplished with reasonable accuracy in a diverse group of subjects of diverse age. Inter- and intraobserver variability approximates that reported previously by Vered et al. (14,15) in studies of normal volunteers. Thus, results of clinical investigation with ultrasonic tissue characterization are likely to be reproducible and consistent among different groups of investigators who use comparable imaging protocols. The observation by Masuyama et al. (17) that cyclic variation declines with advancing age is intriguing. It may
seem surprising at first blush because cyclic variation depends in part on contractile performance, which is generally thought to be well preserved in the absence of disease despite advanced age. However, the hearts of elderly subjects may harbor degenerative changes manifested by or associated with hypertrophy, diastolic dysfunction and “senile amyloidosis,” which may exert subtle influences on systolic contractile performance. Myocardial tissue stiffens with age because of accumulation of collagen (25). In addition, the absolute magnitude of backscatter is determined in part by the collagen content of tissues (4,5,26). Thus, tissue characterization may evolve as a powerful tool for detecting and quantifying structural changes such as collagen deposition accompanying aging, some of which may be responsible for currently only poorly understood functional abnormalities. Masuyama et al. (17) observed a pattern of regional differences in cyclic variation of backscatter characterized by significantly greater cyclic variation in the posterior wall as compared with that in the septum, consistent with results of other reports (14,15,20). Similar regional differences in the magnitude of cyclic variation have been observed from apex to base and intramurally (12,22,27). Such differences appear to parallel regional differences in contractile performance. However, it is not possible to exclude some dependence of the magnitude of cyclic variation observed on the echocardiographic view chosen for imaging (20). The magnitude of both ultrasonic backscatter and attenuation is known to depend in part on the angle of insonification of aligned
JACC Vol. 14, No. 7 December 1989: 1709-l 1
scatterers such as heart fibers that can intluence the magnitude of cyclic variation and may require normalization according to the predominant fiber angle expected with a given view (28-30). View-dependent attenuation of ultrasound as it propagates through the chest may be important as well (31,32). Masuyama et al. (17) report that the “delay” associated with cyclic variation is relatively constant throughout the different myocardial regions characterized and in the different age groups studied. The value for delay (originally called “phase” in references 11 and 33) represents the temporal extent of synchrony of regional and global contractile events (its use as a parameter of regional contractile synchrony is similar conceptually to the use of parameters in two-dimensional phase images acquired from radionuclide ventriculograms subjected to Fourier analysis). Recent results (24) indicate that prolonged delay of cyclic variation is a marker of acute ischemic injury. However, the recovery of delay is typically more rapid than recovery of wall thickening with reperfusion after transient coronary occlusion. Thus, it may provide an early index of viability of stunned myocardium before recovery of mechanical function. The report by Masuyama et al. (17) demonstrates that the value calculated for delay may be relatively insensitive to the particular myocardial region selected for study and may therefore provide a robust measurement of regional contractile properties relatively independent of echocardiographic view. Masuyama et al. (17) emphasize the present lack of a standard approach for analysis of cyclic variation. Various
methods have been used to determine the peak to peak magnitude and the delay of cyclic variation, including Fourier analysis of the fundamental harmonic and manual methods that locate peaks and nadirs of the backscatter curve with respect to electrocardiographic fiducial points. Standardization of analytic methods is critical for acquisition of results that can be compared directly among different groups of investigators. Recently, our group (33,34) described one promising method for determination of the magnitude and cyclic variation that uses a cross-correlation algorithm to fit a model function to the observed data. Implications. Results of the meticulous study by Masuyama et al. (17) underscore the potential clinical utility of ultrasonic tissue characterization of the heart. Judging from the extensive information acquired in many laboratories over the past decade, several clinical conundrums may be resolvable with the help of backscatter imaging implemented to characterize fundamental physical properties of the heart such as microscopic variation in elasticity and density, and three-dimensional microstructural organization. Widespread clinical utilization of this promising approach will undoubtedly stimulate refinement and provide the experience necessary to maximize its diagnostic and prognostic power.
WICKLINE AND SOBEL EDITORIAL COMMENT
JACC Vol. 14, No. 7 December 1989:1709-l i
References I. Wild JJ, Crafford HD, Reid JM. Visualization of the excised human heart by means of reflected ultrasound or echography. Am Heart J 1957; 54:903-6. 2. Mimbs JW. Yuhas DE, Miller JG, Weiss AN, Sobel BE. Detection of myocardial infarction in vitro based on altered attenuation of ultrasound. Circ Res l977:41:192-8. 3. Mimbs JW. O’Donnell M, Miller JG, Sobel BE. Changes in ultrasonic attenuation indicative of early myocardial ischemic injury. Am J Physiol 1979:236:H34&4. 4. O’Donnell M. Mimbs JW. Miller JG. Relationship between collagen and ultrasonic backscatter in myocardial tissue. J Acoust Sot Am 1981: 69:580-8. 5. Mimbs JW, O’Donnell M. Bauwens D, Miller JW, Sobel BE. The dependence of ultrasonic attenuation and backscatter on collagen content in dog and rabbit hearts. Circ Res 1980;47:48-58. 6. Lele PP, Namery, J. A computer-based system for the detection and mapping of myocardial infarcts. Proc San Diego Biomed Symp 1974; 13:121-32. 7. Skorton DJ, Melton HE III. Pandian NB, et al. Detection of acute myocardial infarction in closed-chest dogs by analysis of regional twodimensional echocardiographic gray level distributions. Circ Res 1983: 5213644. 8. Skorton DJ, Collins SM, Nichols J, Pandian NB, Bean JA. Kerber RE. Quantitative texture analysis in two-dimensional echocardiography: application to the diagnosis of experimental myocardial contusion. Circulation 1983:68:217-23 9. Rasmussen S, Lovelace DE, Knoebel SB. Ransburg R, Corya BC. Echocardiographic detection of ischemic and infarcted myocardium. J Am Coll Cardiol 1984;3:733-43. IO. Schnittger IA, Viele A. Heiserman JE. et al. Ultrasonic tissue characterization: detection of acute myocardial ischemia in dogs. Circulation 1985;72:193-9. Il. Fitzgerald PJ, McDaniel MD, Rolett EL, Strohben JW. James DH. Two-dimensional ultrasonic tissue characterization: backscatter power. endocardial motion and their phase relationship for normal. ischemic. and infarcted myocardium. Circulation 1987;76:85C-9. 12. Sagar KB, Rhyne TL, Warltier DC, Pelt L, Wann S. Intramyocardial variability in integrated backscatter: effects of coronary occlusion and reperfusion. Circulation 1987;75:436-42. 13. Olshansky B, Collins SM, Skorton DJ, Prasad NV. Variation of left ventricular myocardial gray level on two-dimensional echocardiograms as a result of cardiac contraction. Circulation 1984;70:97?-7. 14. Vered Z. Barzilai B. Mohr GA. et al. Quantitative ultrasonic tissue characterization with real-time integrated backscatter imaging in normal human subjects and in patients with dilated cardiomyopathy. Circulation 1987;76:1067-73. 15. Vered Z, Mohr GA, Gessler CJ, et al. Ultrasound integrated backscatter tissue characterization of remote myocardial infarction in human subjects J Am Coll Cardiol 1989;13:84-91. 16. Milunski MR, Mohr GA, Gessler CJ, et al. Ultrasonic tissue characterization with integrated backscatter: acute myocardial ischemia. reperfusion, and stunned myocardium in patients. Circulation 1989;80:491-503. 17. Masuyama T. Nellessen IJ, Schnittger 1, Tye TL, Haskell WL, Popp RL. Ultrasonic tissue characterization with a real time integrated backscatter
1711
imaging system in normal and aging human hearts. J Am Coll Cardiol 1989:14:1702-8. 18. Thomas LJ 111.Barzilai B, Perez JE, Sobel BE, Wickline SA, Miller JG. Quantitative real-time imaging of myocardium based on ultrasonic integrated backscatter. IEEE Trans Ultrason Ferroelectr Frequency Control 1989:36:46670. 19. Miller JG. Perez JE, Sobel BE. Ultrasonic characterization of myocardium. Prog Cardiovasc Dis 1985;28:85-IIO. 20. Vandenberg BF. Rath L, Shoup TA. Kerber RE, Collins SM, Skorton DJ. Cyclic variation of ultrasound backscatter in normal myocardium is view dependent: clinical studies using a real-time backscatter imaging system (abstr). J Am Coll Cardiol 3989:13:226A. 21. Madams El. Barzilai B, Perez JE, Sobel BE. Miller JG. Changes in myocardial backscatter throughout the cardiac cycle. Ultrason Imaging 1983:5:229-39. 22. Wickline SA. Thomas LJ III, Miller JG, Perez JE. The dependence of myocardial ultrasonic integrated backscatter on contractile performance. Circulation 1985:72:183-92. 23. Sagar KB, Pelt LE, Rhyne TL, Wann S. Warltier DC. Influence of heart rate. preload, afterload, and inotropic state on myocardial ultrasonic backscatter. Circulation 1988;77:478-83. 24. Milunski MR, Mohr GA. Wear KA, Sobel BE, Miller JG. Wickline SA. Early identification with ultrasonic integrated backscatter of viable but stunned myocardium in dogs. J Am Coll Cardiol 1989:14:462-71. 25. Weber KT. Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol 1989;13:1637-52. 26. Hoyt RM. Skorton DJ. Collins SM, Melton HE. Ultrasonic backscatter and collagen in normal ventricular myocardium. Circulation 1984: 69:775-82. 27. Mottley JG, Glueck RM. Perez JE, Sobel BE, Miller JG. Regional differences in the cyclic variation of myocardial backscatter that parallel regional differences in contractile performance. J Acoust Sot Am 1984: 76:1617-23. 28. Aygen M, Popp RL. Influence of the orientation of myocardial fibers of echocardiographic images. Am J Cardiol 1957;60:147-52. 29. Mottley JG. Miller JG. Anisotropy of the ultrasonic backscatter of myocardial tissue. 1. Theory and measurement in do. J Acoust Sot Am 1988:83:7Sdl. 30. Madaras El. Perez JE, Sobel BE, Mottley JG, Miller JG. Anisotropy of the ultrasonic backscatter of myocardial tissue. II. Measurements in vim. J Acoust Sot Am 1988;83:762-9. 31. Cohen RD. Mottley JG, Miller JG, Kurnik PB. Sobel BE. Detection of ischemic myocardium in viva through the chest wall by quantitative ultrasonic tissue characterization. Am J Cardiol 1982;50:838-43. 32. Melton HE Jr, Skorton DJ. Rational gain compensation for attenuation in cardiac ultrasonography. Ultrason Imaging 1983;5:214-28. 33. Wickline SA, Thomas LJ III, Miller JG, Sobel BE, Perez JE. Sensitive detection of the effects of reperfusion on myocardium by ultrasonic tissue characterization with integrated backscatter. Circulation 1986; 74:389-400. 34. Mohr GA, Vered Z, Barzilai B, Perez JE. Sobel BE. Miller JG. Automated determination of the magnitude and time delay (“phase”) of the cyclic variation of ultrasonic backscatter from myocardium. Ultrason Imaging 1989(in press).