New MR methods to measure myocardial intracelluler [Na+]

测量心肌细胞内的新 MR 方法 [Na ]

• 批准号: 6950740
• 负责人: James Alvin Balschi
• 金额: $ 36.95万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-22 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6950740
• 关键词: bioimaging /biomedical imaging; disease /disorder model; heart imaging /visualization /scanning; intracellular; laboratory mouse; laboratory rat; magnetic resonance imaging; myocardium; myocardium disorder; sodium ion; technology /technique development

DESCRIPTION (provided by applicant): The fundamental premise of this research project is that the intracellular sodium concentration ([Na+]i) provides one of the most sensitive measures of cellular viability. In vivo [Na+]i measurements are, therefore, crucial in the determination of cellular viability. We have developed Na-23 Magnetic Resonance (MR) methods that use shift reagents (SR) to distinguish intra- and extracellular Na+ content and measure [Na+]i in both isolated organs and animals. It is unlikely, however, that SR will ever be applicable for use in humans. Na-23 MR SR methods will be used to provide an "in vivo gold standard" measurement of intra- and extracellular Na+ content of the isolated and intact heart. These will be combined with state of the art H-1 MR relaxography measures of intra and extracellular H20 fractions to yield [Na+]i. Two new Na-23 MR methods for the discrimination and quantification of [Na+]i will be developed. These Na-23 MR methods will exploit the inverse Laplace transform to full advantage. One method will exploit the intrinsic transverse relaxation characteristics of the Na+ resonance; the other will explore use of longitudinal relaxation reagents to aid in Na+ discrimination. The methods will be validated in studies of the isolated perfused heart. The methods will be extended to the intact heart in living animals with the ultimate goal of studies in the human heart. Sodium homeostasis is crucially involved in vital cell functions, such as excitability, excitation- contraction coupling, energy metabolism, pH regulation, as well as cardiac growth and development. Numerous reports indicate that [Na+]i is increased in several cardiac pathologies, which include ischemiaheperfusion injury, hypertrophy, and heart failure. An increase in [Na+]i results in functional consequences, including slowed relaxation, slower recovery from acidosis, as well as, increasing incidence of arrhythmias. Project studies will measure [Na+]i in the hypertrophied and failing myocardium of rats and mice following pressure overload.

描述（由申请人提供）： 该研究项目的基本前提是细胞内钠浓度（[Na+]i）提供了细胞活力的最灵敏的测量方法之一。因此，体内[Na+]i测量在测定细胞活力中至关重要。我们已经开发了Na-23磁共振（MR）方法，该方法使用移位试剂（SR）来区分离体器官和动物中的细胞内和细胞外Na+含量并测量[Na+]i。然而，SR不太可能适用于人类。Na-23 MR SR方法将用于提供离体和完整心脏的细胞内和细胞外Na+含量的“体内金标准”测量。这些将与细胞内和细胞外H2O级分的最新H-I MR弛豫描记术测量组合以产生[Na+]i。两个新的Na-23 MR方法的歧视和定量[Na+]i将开发。这些Na-23 MR方法将充分利用逆拉普拉斯变换。一种方法将利用固有的横向弛豫特性的Na+共振，其他将探讨使用纵向弛豫试剂，以帮助在Na+歧视。该方法将在离体灌流心脏的研究中得到验证。这些方法将扩展到活体动物的完整心脏，最终目标是在人类心脏中进行研究。钠稳态在重要细胞功能中至关重要，例如兴奋性、兴奋-收缩偶联、能量代谢、pH调节以及心脏生长和发育。许多报告表明，[Na+]i在几种心脏病理中增加，包括缺血-再灌注损伤、肥大和心力衰竭。[Na+]i增加会导致功能性后果，包括舒张减慢、从酸中毒恢复较慢以及心律失常发生率增加。项目研究将测量压力超负荷后大鼠和小鼠肥大和衰竭心肌中的[Na+]i。