In vivo proton MRS studies; cerebral injury in HIV Infection

描述(由申请人提供)：本提案是对最近资助的神经艾滋病毒磁共振波谱联合资助(PI：NAVIA R01NS036524-05)的补充。父母资助是对抗逆转录病毒治疗(ART)时代与进展的艾滋病毒疾病相关的大脑代谢物变化和认知损害的纵向研究。本补充资料旨在支持作为母公司财团拨款的一部分自动收集的结构磁共振数据的最先进的纵向分析。目前的研究将使我们能够识别与艾滋病毒相关的脑功能障碍的多个MRI特征，并反过来定义与艾滋病毒有关的大脑参与的进化阶段。抗逆转录病毒疗法极大地提高了艾滋病毒患者的存活率，尽管这些药物对大脑提供持久好处的程度仍未解决。越来越多的证据表明，尽管外围病毒得到了很好的抑制，但仍有大量与艾滋病毒相关的脑损伤继续发生。体内体积磁共振成像(MRI)提供了一种灵敏的测量局部和特定的HIV相关脑异常的方法。MRS联盟正在收集310名艾滋病毒受试者的神经成像、免疫学/病毒学和认知数据，这些受试者有晚期艾滋病毒病史，处于稳定的抗逆转录病毒疗法，以及处于免疫和神经认知损害的不同阶段。随访评估每26-32周进行一次(包括核磁共振)。每个时间点的T1和双回波(质子密度/T2)序列将使用半自动方法进行分析，包括分割、基于体素的形态测量和自动解剖标记，以确定接受治疗的HIV患者的形态测量变化的程度和严重性。主要目标包括：1)研究HIV感染相关的脑实质分数(BPF)、额叶、基底节、海马体和胼胝体萎缩相对于MRS炎症标志物(ml/Cr和Cho/Cr)和神经元健康(NAA/Cr)的演变/进展；2)评估MRS测量变化、体积损失和认知损害进展之间的时间关系；以及3)确定可能预测结构性脑萎缩风险的宿主和病毒因素(如年龄、CD4计数、趋化因子和HIV RNA)。我们建议建立多变量纵向模型，并将HIV的CMS效应作为一个相互关联的因素的动态系统进行检验。在接受抗逆转录病毒治疗的HIV患者中建立神经解剖学后遗症将对认知结果产生关键影响，并为治疗结果提供额外的靶点。

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.