Novel MRS Methods to Characterize MCMD

表征 MCMD 的新 MRS 方法

• 批准号: 7006237
• 负责人: KARL GOODKIN
• 金额: $ 22.73万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-16 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7006237
• 关键词: AIDS dementia complex; attention; basal ganglia; bioimaging /biomedical imaging; clinical research; executive function; glutamates; glutamine; gray matter; human immunodeficiency virus 1; human subject; inositol; language; leukocyte count; magnetic resonance imaging; method development; neural information processing; neuropsychological tests; neurotoxicology; neurotransmitter transport; nuclear magnetic resonance spectroscopy; short term memory; taurine; virus load; white matter

DESCRIPTION (provided by applicant): This is a proposal to advance the use of the techniques of H magnetic resonance spectroscopy (MRS) and MRS imaging (MRSI) in HIV-1 infection. MRS quantification of glutamate - related to neuronal excitotoxicity and cell death - and myo-inositol - related to microglial proliferation - is acknowledged to be of growing significance in HIV-1 infection. To maximize their utility, further refinement is needed of the MRS techniques used to separate glutamine from glutamate and myo-inositol from taurine. After preliminary validation of this methodology, these measures will be related to both clinical [neuropsychological (NP) performance; minor cognitive-motor disorder (MCMD)] and pathophysiological indices (plasma HIV-1 RNA load; CD4 cell count; cytotoxic T lymphocyte count). We will recruit our sample from our renewed NIMH funded R-01 study examining the interaction of aging and HIV-1 infection on the foregoing measures. In that cohort, 327 participants in four groups - older HIV-1+, younger HIV-1+, older HIV-1- and younger HIV-1- - are anticipated to be available over the project period. This proposal will use a 3.0T Siemens Trio system in the frontal grey matter, the frontal subcortical white matter, and the basal ganglia. Those with a diagnosis of MCMD (n=25) will be compared to HIV-1+ individuals without NP impairment (n=25) and to a HIV-1- seronegative control group (n=25). The primary hypotheses relate to the association of increased glutamatergic transmission and myo-inositol concentrations with the diagnosis, symptom profile, and severity of MCMD. Secondary hypotheses relate increased glutamatergic transmission and myo-inositol concentrations to NP performance deficits in the domains of attention, information processing speed, working memory, episodic memory, visuoconstructive skills, abstraction/executive function, language, and motor skills. Support of this study would lead to a subsequent larger, longitudinal R01 proposal aimed at further investigating the impact of this methodological development. This research is significant in that it relates to the potential for increased clinical utility of the non-invasive, brief, in vivo technique of 'H MRS for measuring brain tissue metabolites directly from specified brain regions in order to document the diagnosis of HIV-1 associated MCMD as well as its progression and treatment response.

描述（由申请人提供）：这是一项推进 1H 磁共振波谱（MRS）和 MRS 成像（MRSI）技术在 HIV-1 感染中的应用的提案。谷氨酸（与神经元兴奋性毒性和细胞死亡相关）和肌醇（与小胶质细胞增殖相关）的 MRS 定量被认为在 HIV-1 感染中具有越来越重要的意义。为了最大限度地发挥其效用，需要进一步完善用于分离谷氨酰胺和谷氨酸、肌醇和牛磺酸的 MRS 技术。在对该方法进行初步验证后，这些措施将与临床[神经心理学（NP）表现；轻微认知运动障碍（MCMD）]和病理生理指标（血浆HIV-1 RNA载量；CD4细胞计数；细胞毒性T淋巴细胞计数）。我们将从 NIMH 资助的新 R-01 研究中招募样本，该研究检查衰老和 HIV-1 感染对上述措施的相互作用。在该队列中，预计在项目期间将有 327 名参与者，分为四组：老年 HIV-1+、年轻 HIV-1+、老年 HIV-1- 和年轻 HIV-1-。该提案将在额叶灰质、额叶皮层下白质和基底神经节中使用3.0T西门子Trio系统。那些诊断为 MCMD 的人 (n=25) 将与没有 NP 损伤的 HIV-1+ 个体 (n=25) 和 HIV-1 血清阴性对照组 (n=25) 进行比较。主要假设涉及谷氨酸能传递增加和肌醇浓度与 MCMD 的诊断、症状特征和严重程度之间的关联。次要假设将谷氨酸能传递和肌醇浓度增加与注意力、信息处理速度、工作记忆、情景记忆、视觉建构技能、抽象/执行功能、语言和运动技能等领域的 NP 表现缺陷联系起来。对这项研究的支持将导致后续更大的、纵向的 R01 提案，旨在进一步调查这种方法发展的影响。这项研究具有重要意义，因为它涉及增加非侵入性、简短的体内 H MRS 技术的临床实用性的潜力，该技术可直接测量特定大脑区域的脑组织代谢物，以记录 HIV-1 的诊断相关的 MCMD 及其进展和治疗反应。