Structural Basis of Ventricular Function

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DESCRIPTION (provided by applicant): Elucidating the structure-function relationship in heart is key to the understanding of the underlying mechanisms of myocardial dysfunction. The pathologic progression of cardiac diseases is frequently associated with alterations/disruptions in myocardial fiber structure. Because the contractile property of the heart is prominently influenced by the unique organization of myocardial fibers, these structural changes frequently lead to abnormal ventricular function at both regional and global levels. However, characterization and identification of subtle changes in fiber architecture at sub-millimeter resolution have been challenging. The standard histological techniques are destructive and labor intensive. Therefore, they are not adequate for fast and 3D characterization of structural changes during ventricular contraction. As a result, the structure-function relationship in diseased hearts remains poorly defined. No direct association could be made between regional contractile abnormalities and alterations in myocardial fiber structure. The overall objective of the proposed study is to develop state-of-the-art MRI methods to explore the structural basis of myocardial function in both normal and diseased hearts. We have recently developed diffusion tensor magnetic resonance imaging (DTMRI) methods for 3D delineation of myocardial fiber and sheet architecture in perfused viable hearts. This technique was applied to elucidate the structural basis of myocardial wall thickening by directly assessing myocardial structural changes from diastole to systole. Further, we have also established in vivo MR tagging methods to assess regional myocardial wall motion in small animals such as rats and mice. In this project, we will further the application of DTMRI to delineate dynamic structural changes in perfused, contracting hearts. This technique will be used to characterize structural and functional changes in normal hearts by combining DTMRI studies with MR tagging characterization of regional myocardial function. Furthermore, the structure-function relationship will also be investigated in two disease models: 1) the hypertrophic hearts, induced by aortic banding, with global structural changes; and 2) the post-infarct hearts, created by LAD ligation, with focal infarct lesions.