Structural Basis of Ventricular Function

描述(由申请人提供)：阐明心脏的结构-功能关系是了解心肌功能障碍的潜在机制的关键。心脏疾病的病理进展通常与心肌纤维结构的改变/破坏有关。由于心脏的收缩特性受到心肌纤维独特组织的显著影响，这些结构变化经常导致局部和整体水平的心功能异常。然而，在亚毫米分辨率下表征和识别光纤结构的细微变化一直是具有挑战性的。标准的组织学技术是破坏性的和劳动密集型的。因此，它们不足以快速和3D地描述心室收缩过程中的结构变化。因此，疾病心脏的结构-功能关系仍然不明确。在局部收缩异常和心肌纤维结构改变之间没有直接的联系。这项拟议研究的总体目标是开发最先进的MRI方法，以探索正常和疾病心脏的心肌功能的结构基础。我们最近开发了扩散张量磁共振成像(DTMRI)方法，用于在灌流的存活心脏中三维描绘心肌纤维和片状结构。应用这项技术，通过直接评估从舒张期到收缩期的心肌结构变化，阐明心肌壁增厚的结构基础。此外，我们还建立了在体MR标记方法来评估小动物如大鼠和小鼠的局部心肌壁运动。在这个项目中，我们将进一步应用DTMRI来描绘灌流、收缩的心脏的动态结构变化。这项技术将通过结合DTMRI研究和MR标记局部心肌功能的特征，来表征正常心脏的结构和功能变化。此外，还将在两种疾病模型中研究结构与功能的关系：1)由主动脉环扎引起的肥大心脏，具有整体结构变化；2)由左前降支结扎造成的梗塞后心脏，具有局灶性梗塞病变。

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.