FMRI INDICES AND CSF VIRAL LOAD IN HIV-INFECTION

性状（由申请方提供）：高水平CSF HIV-1 RNA，和 相关的神经行为缺陷，已经报道，没有相称的 血清病毒水平（Ellis等，2000; Ellis等人，1997;麦克阿瑟等人， 1997; Staprans等人，1999; Wong等人，1997年）。这意味着连环杀手 腰椎穿刺，虽然侵入性，可能是最好的方法， 监测HIV相关神经退行性病变的进展。 用于检测和监测HIV相关CNS的灵敏的非侵入性方法 需要效果。拟议研究的目的是评估 应用结构（SMRI）和功能（FMRI）成像方法， 预测CNS病毒复制。该方法是由以前的研究指导的 表明纹状体神经变性和弥漫性大脑白色 物质损伤是两种最一致的结构异常， 该群体（Jernigan等人，1993; Stout等人，（1998）心理学 减速是最突出的功能缺陷。由于CSF HIV-1 RNA是 目前最好的可用指标中枢神经系统病毒复制，这一措施将 是拟议研究的主要因变量。组 神经行为受损和未受损的血清阳性个体，以及 血清阴性对照，将在24小时内进行重复sMRI/fMRI检查， 基线以及开始（血清阳性受试者）后6周和12周 积极的HAART治疗，旨在降低CSF HIV-1 RNA水平。措施 白色信号改变，尾状核体积，任务相关 尾状核中血氧的变化（在运动任务期间）将是 与血清阳性受试者的CSF HIV-1 RNA水平相关。的 这些SMRI和FMRI指标在预测CSF病毒水平方面的效用将是 与行为指标相比，可能与其他指标相比， 非侵入性方法（如MR光谱），单变量和多变量 预测模型

DESCRIPTION (Provided by applicant): 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.