FMRI INDICES & CSF VIRAL LOAD IN HIV-INFECTION

这个子项目是许多利用 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。 已经报道了高水平的CSF HIV-1 RNA和相关的神经行为缺陷，而没有相应的血清病毒水平（Ellis等人，2000; Ellis等人，1997;麦克阿瑟等人，1997; Staprans等人，1999; Wong等人，1997年）。这意味着，连续腰椎穿刺，虽然侵入性，可能是最好的方法来监测艾滋病毒相关的神经退行性疾病的进展。需要灵敏的非侵入性方法来检测和监测HIV相关的CNS效应。拟议的研究的目的是评估应用结构（SMRI）和功能（FMRI）成像方法预测中枢神经系统病毒复制。该方法由先前的研究指导，该研究表明纹状体中的神经变性和弥漫性脑白色物质损伤是存在于该人群中的两种最一致的结构异常（Jernigan等人，1993; Stout等人，1998年）和心理放缓是最突出的功能缺陷。由于CSF HIV-1 RNA是目前CNS病毒复制的最佳可用指标，因此该指标将成为拟定研究的主要因变量。将对神经行为受损和未受损血清阳性个体以及血清阴性对照组进行研究，在基线时以及开始（血清阳性受试者）旨在降低CSF HIV-1 RNA水平的积极HAART治疗后6周和12周进行重复sMRI/fMRI检查。将尾状核中的白色信号变化、尾状核体积和任务相关的血氧变化（在运动任务期间）的测量与血清阳性受试者中的CSF HIV-1 RNA水平相关。在单变量和多变量预测模型中，将这些SMRI和FMRI指标在预测CSF病毒水平方面的效用与行为指标进行比较，并可能与其他非侵入性方法（如MR波谱）进行比较。

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. High levels of CSF HIV-1 RNA, and associated neurobehavioral deficits, have been reported without commensurate serum viral levels (Ellis et al., 2000; Ellis et al., 1997; McArthur et al., 1997; Staprans et al., 1999; Wong et al., 1997). The implication is that serial lumbar puncture, although invasive, may be the best available method for monitoring the progression of HIV-related neurodegenerative processes. Sensitive noninvasive methods for detecting and monitoring HIV-related CNS effects are needed. The aim of the proposed studies is to evaluate the application of structural (SMRI) and functional (FMRI) imaging methods for predicting CNS viral replication. The approach is guided by previous studies suggesting that neurodegeneration in the striatum and diffuse cerebral white matter damage are the two most consistent structural abnormalities present in this population (Jernigan et al., 1993; Stout et al., 1998) and psychomotor slowing is the most prominent functional deficit. Since CSF HIV-1 RNA is currently the best available index of CNS viral replication, this measure will be the primary dependent variable for the proposed studies. Groups of neurobehaviorally impaired and unimpaired seropositive individuals, and yoked seronegative controls, will be studied with repeated sMRI/fMRI examinations at baseline, and 6 and 12 weeks after initiation (in the seropositive subjects) of aggressive HAART therapy aimed at reducing CSF HIV-1 RNA levels. Measures of white matter signal change, of caudate nucleus volume, and of task-related change in blood oxygenation in the caudate nucleus (during motor tasks) will be correlated with levels of CSF HIV-1 RNA within the seropositive subjects. The utility of these SMRI and FMRI measures in predicting CSF viral levels will be compared with that of behavioral measures, and possibly with that of other noninvasive methods (such as MR spectroscopy), in univariate and multivariate prediction models.