ULTRASONIC INTEGRATED BACKSCATTER IMAGING CHARACTERIZING MYOCARDIUM:THE CLINICAL IMPLICATIONS AND APPLICATIONS FOR CELLULAR BIOLOGY

• Main Authors: Lung-Chun Lin, 林隆君
• Other Authors: 李源德
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/88828346319536022889

博士 === 國立臺灣大學 === 臨床醫學研究所 === 94 === In patients with coronary artery disease, postischemic dysfunction (stunned myocardium) and chronic hypoperfusion (hibernating myocardium) are two major pathophysiologic states in which viable myocardium demonstrates reduced contractility. It has long been recognized that the working myocardium behaves as an electrical syncytium. Ultrasonic tissue characterization (UTC) with integrated backscatters (IBS) has shown to be a promising approach in detecting various forms of myocardial pathology by delineating the physical properties and intramural contractility. Normal myocardium exhibits cardiac cycle-dependent variation of integrated backscatter that will be blunted in amplitude and have temporal shift in the nadir by experimental ischemia. Reperfusing the acutely infarcted myocardium will restore the cyclic variation before the wall motion recovery that implicates the stunned myocardium. In the setting of hibernating myocardium, some investigations have declared that UTC measures the intramural contractility that is relatively independent of resting wall motion and parallels contractile reserve. Rose et al. validated the simulation model and proposed that, with the microscopic elastic wave theory, the size and interdistance of scatters (myocytes), the impedance mismatching between the myocytes'' intracellular contents and the extracellular collagen networks as well as the ultrasonic insonification angle determine the acoustic contrast responsible for the scattering and generate the cardiac cycle-dependent variation. After introducing the prototype ultrasound machine capable of collecting and processing the raw data of radiofrequency to generate the IBS imaging since 1996, we have been studying the alteration of myocardial ultrasonic backscatters in various cardiac diseases, including detecting multivessel coronary artery disease and TIMI 3 flow of infarct-related artery, evaluating the viability and residual ischemia in the setting of acute myocardial infarction. For the patients having coronary stable angina, we have validated that the results of UTC are influenced by myocardial viability and ischemic burden, indicating the intramural contractility. The inhomogeneous intramural contraction and the degeneration of myocardial structure followed by the loss of viability, implicating the ischemic progress in myocardial pathology, may influence the alterations of UTC by relieving the coronary stenosis. We performed a study to delineate the alterations of myocardial UTC relating to the coronary revascularization and restenosis in patients having chronic coronary heart disease, staging by the development of wall motion abnormality and the absence of contractile reserve and comparable to our previous investigations in cases of acute myocardial infarction, and found that (1) although the baseline wall motion was normal, the myocardium with coronary obstruction might develop intramural contractile dysfunction shown by abnormal modulation in the IBS power curve; (2) relieving the coronary stenosis in viable myocardium would restore its cyclic variations of IBS; (3) the nonviable myocardium had prominent deviation and small weighted amplitude irrelevant to the coronary patency. We have observed that hypercholesterolemia can induce myocardial electrical remodeling, which was associated with prolonged action potential duration, longer QTc intervals, increased repolarization dispersion, and increased vulnerability to ventricular fibrillation. The dietary hypercholesterolemia has been also shown to induce contractile dysfunction independent of vascular disease, characterized by a decrease in the maximum rate of shortening and relaxation. We also showed that diet-induced hypercholesterolemia in rabbits caused down-regulation of myocardial Cx43 protein and redistribution of Cx43 gap junction, up-regulation of Cx43 transcripts, and activation of JNK. The hypercholesterolemic rabbit hearts, in vivo demonstrated to have systolic dysfunction by using the CVI, mitral ring systolic velocity, and modified Tei index, and suggest that the remodeling of cardiomyocyte gap junctions may contribute to the impaired systolic function. Because gap junctions play a pivotal role in the coordinated excitation of the heart, their remodeling by hypercholesterolemia may partly explore the beneficial effects of lipid-lowering therapy in heart diseases. There are three important implications by our investigations. First of all, we have validated the clinical application of UTC to access intramural contractile events in various conditions of ischemic heart disease including distinguishing the stunned myocardium, detecting the early successful reperfusion of infarct-related artery and multivessel coronary artery disease for patients with acute myocardial infarction, as well as risk stratification and interventional strategy for the jeopardized infarct myocardium. In the setting of chronic coronary artery disease, the UTC, influenced by myocardial viability and ischemic burden, can be used to predict the functional recovery of dyssynergic myocardium after revascularization and detected coronary restenosis. Secondly, we applied the UTC as a tool for in vivo functional assessment of animal model and found the correlation between remodeling of gap junction and impairment of myocardial contractility in rabbits subjecting to a cholesterol-enriched diet. The study of intercellular contractile synchronism, beyond the intracellular mechanisms that were studied in cultured cells, may be demonstrated via the imaging modality, opening a new horizon in delineating the cellular interaction functionally in tissue preparations, isolated perfused organs or living animals. This progress will be accompanied with the advanced genetic manipulation such as transgenic models or controlled expression in the functional proteonomic era. Finally, there is much progress in the process of radiofrequency raw signals after the fantastically growing capability of computer technique. Our studies has proved the IBS data informative, which will be enriched under the high-frame rate imaging acquisition and serve as the base of speckle recognition and tracking to construct the multi-dimensional myocardial strain imaging instead of those derived from Doppler ultrasound.