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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 尚未开发出用于跟踪疾病进展的可靠的、非侵入性的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提供深入了解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）的高场磁体，非侵入性地测量整个生命周期中大脑化学物质的浓度。先前在纹状体（HD中受影响最大的大脑区域）中的1H MRS研究揭示了HD小鼠寿命期间早期和异步的化学变化。我们建议试点高分辨率1H MRS协议，将允许未来的纵向研究，以遵循化学变化，从症状前到早期疾病阶段的个人在HD的风险。这些转化研究的潜力将是开发一种用于分析小鼠和人类疾病进展的工具，同时增强对HD发病机制的理解。 我们建议探索在人类中使用3 T的1H MRS，以实现以下目标： 目标1：使用3 T下的1H MRS评价基因阴性对照和基因阳性早期HD受试者的纹状体（尾状核和壳核）和皮质（枕叶和感觉运动）区域的代谢产物谱。 目标二：根据基因阴性对照和基因阳性早期HD受试者中早期HD脑区域的选定1H磁共振波谱，确定代谢物浓度的受试者间变异性。