In vivo proton MRS studies; cerebral injury in HIV Infection

体内质子 MRS 研究；

• 批准号: 7168025
• 负责人: BRADFORD NAVIA
• 金额: $ 48.64万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7168025
• 关键词: vivo; proton; MRS; studies; cerebral

DESCRIPTION (provided by applicant): The present proposal is a supplement to the recently funded NeuroHIV Magnetic Resonance Spectroscopy Consortium grant (PI: Navia R01NS036524-05). The parent grant is a longitudinal study of brain metabolite changes and cognitive impairment associated with advancing HIV disease in the era of anti-retroviral therapy (ART). This supplement aims to support state-of-the-art longitudinal analyses of the structural MRI data that is automatically collected as part of the parent consortium grant. The present study will allow us to identify multiple MRI signatures of brain dysfunction associated with HIV, and in turn define the evolutionary stages of brain involvement in HIV. ART has dramatically improved survival rates among HIV patients, though the extent to which these agents provide lasting benefits to the brain remains unresolved. There is accumulating evidence that despite good peripheral viral suppression, a significant amount of HIV-associated brain injury continues to occur. In vivo volumetric magnetic resonance imaging (MRI) provides a sensitive measure of regional and specific HIV- associated brain abnormalities. The MRS Consortium is collecting neuroimaging, immunological/virological and cognitive data from 310 HIV subjects with a history of advanced HIV disease on stable ART and at different stages of immunological and neurocognitive compromise. Follow-up assessments occur every 26-32 weeks (including MRI). The T1 and dual echo (proton density/T2) sequences from each time point will be analyzed using semi-automated methods including segmentation, voxel based morphometry and automatic anatomical labeling in order to ascertain the extent and severity morphometric change in treated HIV patients. The primary aims include: 1) To examine the evolution/progression of brain parenchymal fraction (BPF), frontal lobe, basal ganglia, hippocampal, and corpus callosum atrophy associated with HIV infection relative to MRS markers of inflammation (Ml/Cr, and Cho/Cr) and neuronal health (NAA/Cr); 2) To assess the temporal relationships between change in MRS measures, volumetric loss, and progression of cognitive impairment; and 3) To identify host and viral factors (e.g., age, CD4 count, chemokines, and HIV RNA) that may predict risk for structural brain atrophy. We propose to derive multivariate longitudinal models and examine the CMS effects of HIV as a dynamic system of interrelated factors. The establishment of neuroanatomical sequelae among HIV subjects on ART will have critical ramifications for cognitive outcome as well as provide additional targets for therapeutic outcome.

描述（由申请人提供）：本提案是对最近资助的NeuroHIV磁共振光谱联盟资助（PI：Navia R 01 NS 036524 -05）的补充。父母补助金是一项纵向研究，研究抗逆转录病毒治疗（ART）时代与艾滋病进展相关的脑代谢物变化和认知障碍。该补充旨在支持结构MRI数据的最先进的纵向分析，这些数据是作为母财团赠款的一部分自动收集的。目前的研究将使我们能够识别与HIV相关的脑功能障碍的多种MRI特征，并反过来定义HIV大脑参与的进化阶段。抗逆转录病毒疗法显著提高了艾滋病患者的存活率，尽管这些药物对大脑的持久益处程度仍有待解决。越来越多的证据表明，尽管外周病毒抑制良好，但仍有大量HIV相关的脑损伤继续发生。在体内体积磁共振成像（MRI）提供了一个敏感的措施，区域和特定的艾滋病毒相关的脑异常。MRS联盟正在收集来自310名HIV受试者的神经影像学、免疫学/病毒学和认知数据，这些受试者有晚期HIV病史，正在接受稳定的ART治疗，处于免疫学和神经认知损害的不同阶段。每26-32周进行一次随访评估（包括MRI）。将使用半自动方法（包括分割、基于体素的形态测定和自动解剖标记）分析每个时间点的T1和双回波（质子密度/T2）序列，以确定接受治疗的HIV患者的形态测定变化的程度和严重程度。主要目标包括：1）检查与HIV感染相关的脑实质部分（BPF）、额叶、基底节、海马和胼胝体萎缩相对于炎症的MRS标志物的演变/进展（MI/Cr和Cho/Cr）和神经元健康（NAA/Cr）：2）评估MRS测量的变化、体积损失和认知损害进展之间的时间关系;和3）鉴定宿主和病毒因子（例如，年龄、CD 4计数、趋化因子和HIV RNA），可能预测结构性脑萎缩的风险。我们建议推导出多变量纵向模型，并将艾滋病病毒的CMS效应作为一个相互关联的因素的动态系统进行研究。在接受ART的HIV受试者中建立神经解剖学后遗症将对认知结果产生重要影响，并为治疗结果提供额外的靶点。