Non-Invasive NMR Imaging of Cardiac Remodeling in Aging

衰老过程中心脏重塑的无创核磁共振成像

• 批准号: 6439811
• 负责人: JOHN Robert FORDER
• 金额: $ 7.18万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6439811
• 关键词: age difference; aging; bioimaging /biomedical imaging; cardiovascular disorder diagnosis; cardiovascular imaging /visualization; collagen; diffusion; extracellular matrix; fibrosis; heart; heart contraction; heart enlargement; histology; hydroxyproline; hypertension; isolation perfusion; laboratory rat; magnetic resonance imaging; morphometry; myocardium; noninvasive diagnosis; nuclear magnetic resonance spectroscopy; pathologic process; ventricular hypertrophy; water

This project is directed toward the effects of aging on the cardiovascular system and age-related changes in extracellular matrix. Normal aging results in myocyte loss, increased fibrosis and myocardial stiffness, and depressed contractility. Aging is also associated with a significant increase in the incidence of cardiac hypertrophy, often accompanied by changes in the extracellular matrix such as increased collagen deposition and fibrosis. Thus, myocardial remodeling plays an important role in the development of cardiac dysfunction seen with increased age. However, the distinct between normal aging and the effects of underlying disease processes is difficult to assess. Currently the only quantitative methods available to assess the extent of remodeling are histological or biochemical, and require fixation or extraction of tissue samples. Clearly such methods are not optimal for the investigation of relationships between aging, left ventricular (LV) remodeling, and contractile function in humans. Magnetic resonance imaging (MRI) has great clinical potential for the non-invasive detection and monitoring of cardiac disease and its response to therapy. In addition to high quality anatomic information, it can also be used to obtain quantitative information of both global and regional LV function. Recently, we demonstrated that MRI could detect changes in the diffusion of water during myocardial ischemia. In exciting new studies, we demonstrated that diffusion MRI could be used to determine myocardial fiber angle orientation with a high degree of precision, and the use of high diffusion gradients uncovers multiple diffusion components that correlate to different compartments in the tissue (extracellular, intracellular, etc.) The main hypotheses of this proposal are: 1) that decreased diffusion of water will be correlated with a increase in collagen accumulation and fibrosis, and 2) that measurements of myocardial fiber angle orientation combined with diffusion measurements will be used to distinguish between the effects of normal aging and the development of cardiac hypertrophy. In order to test these hypotheses diffusion tensor MRI experiments will be carried out on perfused hearts isolated from 6 and 18 month old spontaneously hypertensive rats (SHR) and age-matched non- hypertensively Wister-Kyoto rats. Hydroxyproline content of the myocardium will be used as a measure of the total tissue collagen content. This proposal will provide the foundation for the application of diffusion MRI in the quantitative evaluation of both normal and pathophysiological remodeling that occurs in the myocardium. The ability to non-invasively determine changes in the extracellular matrix of the myocardium coupled with measurements of fiber orientation will constitute a major advance in understanding the effects of aging on cardiac structure and function.

该项目针对衰老对心血管系统的影响以及细胞外基质中与年龄有关的变化。正常的衰老会导致心肌细胞丧失，纤维化增加和心肌僵硬以及收缩性降低。衰老还与心脏肥大的发生率显着增加有关，通常伴随着细胞外基质的变化，例如胶原蛋白沉积和纤维化的增加。因此，心肌重塑在年龄增加的心脏功能障碍的发展中起着重要作用。但是，很难评估正常衰老与潜在疾病过程的影响之间的不同。目前，可用于评估重塑程度的唯一定量方法是组织学或生化，需要固定或提取组织样品。显然，对于研究人类衰老，左心室（LV）重塑和收缩功能之间的关系，这种方法并不是最佳的。磁共振成像（MRI）具有非侵入性检测和监测心脏疾病及其对治疗反应的巨大临床潜力。除了高质量的解剖信息外，还可以用于获得全球和区域LV功能的定量信息。最近，我们证明MRI可以检测到心肌缺血期间水扩散的变化。在令人兴奋的新研究中，我们证明了扩散MRI可用于确定心肌纤维角度方向和高度精确度，并且使用高扩散梯度的使用发现了多个与细胞外，细胞内的扩散成分相关的多个扩散成分，这些成分与细胞外，胞内等的主要水平相关的是：1 corl tive conter and Infor poter confer and coll and collf Fiff collf Fiff tiff Fiff Fiff Fiff Fiff Fiff Fiff。累积和纤维化，以及2）将使用扩散测量的心肌纤维角方向的测量来区分正常衰老的影响和心脏肥大的发展。为了测试这些假设，将在从6个月和18个月大的自发性高血压大鼠（SHR）和年龄匹配的非高度敏感性的矮鼻型大鼠中分离出的灌注心脏中进行扩散张量张量。心肌的羟基含量将用作总体组织胶原蛋白含量的量度。该建议将为扩散MRI在心肌中发生的正常和病理生理重塑的定量评估中提供基础。非侵入性确定心肌的细胞外基质的变化以及纤维方向测量的能力将构成重大的进步，以理解衰老对心脏结构和功能的影响。