1H MAGNETIC RESONANCE SPECTROSCOPY OF EARLY HD

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 一种可靠的、非侵入性的跟踪疾病进展的生物标志物还没有被开发出来用于评估亨廷顿病(HD)的患者和小鼠模型。有用的生物标记物可以在监测症状前状态进展的同时，为HD的发病机制提供洞察力。质子磁共振波谱(1HMRS)使用核磁共振研究中心(CMRR)的高场磁铁，非侵入性地测量生命周期中大脑化学物质的浓度。之前对纹状体(HD最受影响的大脑区域)的1H MRS研究揭示了HD小鼠生命过程中早期和不同步的化学变化。我们建议试行高分辨率1H MRS方案，这将允许未来的纵向研究跟踪HD风险个体从症状前到疾病早期的化学变化。这些翻译研究的潜力将是开发一种工具，用于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3T的1H MRS在人类中的应用，以实现以下目标： 目的：用3T核磁共振波谱技术评价基因阴性对照和基因阳性早期HD患者纹状体(尾状核和壳核)和皮质(枕区和感觉运动区)的代谢产物分布。 目的：从基因阴性对照和基因阳性早期HD受试者的早期脑区核磁共振波谱中确定代谢物浓度的研究对象间的变异性。

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.