Structural Basis of Ventricular Function

描述（申请人提供）：阐明心脏结构-功能关系是了解心肌功能障碍潜在机制的关键。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全局水平的心室功能异常。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具有挑战性。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表征心室收缩期间的结构变化。因此，患病心脏的结构-功能关系仍然不明确。局部收缩异常与心肌纤维结构改变无直接联系。提出的研究的总体目标是发展最先进的MRI方法来探索正常和患病心脏心肌功能的结构基础。我们最近开发了弥散张量磁共振成像（DTMRI）方法，用于三维描绘灌注活心脏的心肌纤维和片结构。该技术通过直接评价心肌舒张期至收缩期的结构变化，阐明心肌壁增厚的结构基础。此外，我们还建立了体内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来描绘灌注收缩心脏的动态结构变化。该技术将通过DTMRI研究与区域心肌功能的MR标记表征相结合，用于表征正常心脏的结构和功能变化。此外，结构-功能关系也将在两种疾病模型中进行研究：1)由主动脉瓣带引起的肥厚心脏，具有全局结构变化；2)由LAD结扎产生的梗死后心脏，灶性梗死灶。

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.