1H MAGNETIC RESONANCE SPECTROSCOPY OF EARLY HD

早期 HD 的 1H 磁共振波谱

• 批准号: 7954953
• 负责人: JANET M DUBINSKY
• 金额: $ 1.28万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954953
• 关键词: Affect; Biological Markers; Brain; Brain region; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Disease; Disease Progression; Funding; Future; Genes; Grant; Human; Huntington Disease; Individual; Institution; Longevity; Longitudinal Studies; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Monitor; Mus; Pathogenesis; Patients; Protocols documentation; Protons; Research; Research Personnel; Resolution; Resources; Risk; Source; Spectrum Analysis; Staging; United States National Institutes of Health; insight; mouse model; putamen; tool; translational study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A reliable, noninvasive biomarker for following disease progression has not been developed for evaluating both patients and mouse models of Huntington's Disease (HD). Useful biomarkers should provide insights into HD pathogenesis while monitoring progression from a presymptomatic state. Proton magnetic resonance spectroscopy (1H MRS), using high field magnets at the Center for Magnetic Resonance Research (CMRR), non-invasively measures concentrations of brain chemicals across the lifespan. Previous 1H MRS studies in the striatum, the brain region most affected in HD, revealed chemical changes early and asynchronously over the lifespan of HD mice. We propose to pilot high resolution 1H MRS protocols that will permit future longitudinal studies to follow chemical changes from presymptomatic to early disease stages in individuals at risk for HD. The potential of these translational studies will be to develop a tool for analyzing disease progression in mice and humans, while enhancing understanding of HD pathogenesis. We propose to explore the use of 1H MRS at 3T in humans for the following aims: Aim 1: To evaluate metabolite profiles in striatal (caudate and putamen) and cortical (occipital and sensorimotor) regions in gene negative controls and gene positive early stage HD subjects using 1H MRS at 3T. Aim 2: To determine the intersubject variability in metabolite concentrations from the selected 1H Magnetic Resonance Spectroscopy of Early HD brain regions in gene negative controls and gene positive early stage HD subjects.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目前尚未开发出一种可靠的、非侵入性的疾病进展生物标志物来评估亨廷顿病 (HD) 的患者和小鼠模型。有用的生物标志物应该可以深入了解 HD 发病机制，同时监测症状前状态的进展。质子磁共振波谱 (1H MRS) 使用磁共振研究中心 (CMRR) 的高场磁铁，无创地测量整个生命周期中大脑化学物质的浓度。先前对纹状体（HD 中受影响最严重的大脑区域）进行的 1H MRS 研究揭示了 HD 小鼠在整个生命周期中早期和异步的化学变化。我们建议试点高分辨率 1H MRS 方案，这将使未来的纵向研究能够跟踪有 HD 风险的个体从症状前到疾病早期阶段的化学变化。这些转化研究的潜力将是开发一种工具来分析小鼠和人类的疾病进展，同时增强对 HD 发病机制的理解。 我们建议探索 1H MRS 在 3T 下在人类中的应用，以实现以下目标： 目标 1：使用 3T 1H MRS 评估基因阴性对照和基因阳性早期 HD 受试者纹状体（尾状核和壳核）和皮质（枕叶和感觉运动）区域的代谢谱。 目标 2：确定基因阴性对照和基因阳性早期 HD 受试者中早期 HD 大脑区域选定的 1H 磁共振波谱中代谢物浓度的受试者间差异。