Structural Basis of Ventricular Function

心室功能的结构基础

• 批准号: 7408061
• 负责人: Xin Yu
• 金额: $ 43.7万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-18 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7408061
• 关键词: Animals; Architecture; Area; Arts; Cardiac; Condition; Contracts; Development; Diastole; Diffusion; Disease model; Disruption; Fiber; Fibrosis; Global Change; Heart; Heart Diseases; Histological Techniques; Hypertrophy; Image; Imaging Techniques; Infarction; Lead; Left ventricular structure; Lesion; Ligation; Magnetic Resonance Imaging; Measures; Methods; Microscopic; Modeling; Motion; Mus; Myocardial; Myocardial Infarction; Myocardial dysfunction; Operative Surgical Procedures; Pathologic; Performance; Physiologic pulse; Property; Pulse taking; Rattus; Research Personnel; Resolution; Series; Staging; Standards of Weights and Measures; Structure; Structure-Activity Relationship; Study of magnetics; Systole; Techniques; Tissues; Ventricular; Ventricular Function; Work; base; in vivo; loss of function; millimeter; pressure; tissue preparation; water diffusion

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.

描述（由申请人提供）：阐明心脏的结构-功能关系是理解心肌功能障碍的潜在机制的关键。心脏病的病理进展常常与心肌纤维结构的改变/破坏相关。由于心脏的收缩特性显着受到心肌纤维独特组织的影响，这些结构变化经常导致局部和整体水平的心室功能异常。然而，以亚毫米分辨率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并且是劳动密集型的。因此，它们不足以快速表征心室收缩期间的结构变化。因此，患病心脏的结构与功能关系仍然不明确。局部收缩异常与心肌纤维结构改变之间没有直接关联。该研究的总体目标是开发最先进的 MRI 方法，以探索正常和患病心脏心肌功能的结构基础。我们最近开发了扩散张量磁共振成像 (DTMRI) 方法，用于对灌注活心脏中的心肌纤维和片状结构进行 3D 描绘。该技术用于通过直接评估从舒张期到收缩期的心肌结构变化来阐明心肌壁增厚的结构基础。此外，我们还建立了体内 MR 标记方法来评估大鼠和小鼠等小动物的局部心肌壁运动。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。该技术将通过将 DTMRI 研究与区域心肌功能的 MR 标记特征相结合，用于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-功能关系：1）由主动脉束带引起的肥厚心脏，具有整体结构变化； 2) 通过 LAD 结扎产生的梗塞后心脏，具有局灶性梗塞病变。