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.

该项目旨在研究衰老对心血管系统的影响以及细胞外基质中与年龄相关的变化。正常衰老会导致心肌细胞损失、纤维化和心肌僵硬度增加以及收缩力下降。衰老还与心脏肥大的发生率显着增加相关，通常伴有细胞外基质的变化，例如胶原沉积和纤维化增加。因此，心肌重塑在随着年龄增长而出现的心功能障碍的发展中起着重要作用。然而，正常衰老与潜在疾病过程的影响之间的区别很难评估。目前可用于评估重塑程度的唯一定量方法是组织学或生物化学，并且需要固定或提取组织样本。显然，此类方法对于研究人类衰老、左心室 (LV) 重塑和收缩功能之间的关系并不是最佳的。磁共振成像（MRI）在非侵入性检测和监测心脏病及其治疗反应方面具有巨大的临床潜力。除了高质量的解剖信息外，它还可用于获取全局和局部左心室功能的定量信息。最近，我们证明 MRI 可以检测心肌缺血期间水扩散的变化。在令人兴奋的新研究中，我们证明扩散 MRI 可用于高精度确定心肌纤维角度方向，并且使用高扩散梯度揭示了与组织中不同区室（细胞外、细胞内、等）该提案的主要假设是：1）水扩散的减少与胶原蛋白积累和纤维化的增加相关，2）心肌纤维角度方向的测量与扩散测量相结合将用于区分正常衰老和心脏肥大发展的影响。为了测试这些假设，将对从 6 个月和 18 个月大的自发性高血压大鼠 (SHR) 和年龄匹配的非高血压 Wister-Kyoto 大鼠分离的灌注心脏进行弥散张量 MRI 实验。心肌的羟脯氨酸含量将用作总组织胶原含量的量度。该提案将为扩散磁共振成像在心肌中发生的正常和病理生理重塑的定量评估中的应用提供基础。非侵入性确定心肌细胞外基质变化的能力与纤维取向的测量相结合，将在理解衰老对心脏结构和功能的影响方面取得重大进展。