FMRI INDICES AND CSF VIRAL LOAD IN HIV-INFECTION

描述(申请人提供)：高水平的脑脊液HIV-1 RNA，以及 相关的神经行为缺陷，已经被报道没有相称的 血清病毒水平(Ellis等人，2000；Ellis等人，1997；McArthur等人， 1997年；Staprans等人，1999年；Wong等人，1997年)。言下之意就是这一系列 腰椎穿刺术虽然具有侵入性，但可能是治疗 监测艾滋病毒相关神经退行性变过程的进展。 检测和监测HIV相关中枢神经系统的灵敏无创性方法 效果是需要的。建议研究的目的是评估 结构性(SMRI)和功能性(FMRI)成像方法的应用 预测中枢神经系统病毒复制。这种方法是以以前的研究为指导的 提示纹状体和弥漫性脑白质的神经变性 物质损伤是两种最一致的结构异常 这一人群(Jernigan等人，1993；Stout等人，1998)和精神运动 经济放缓是最突出的功能赤字。由于脑脊液HIV-1 RNA是 目前最好的CNS病毒复制指数，这一措施将 是拟议研究的主要因变量。几组人 神经行为受损和未受损的血清阳性个体，以及枷锁 血清阴性对照将通过重复sMRI/fMRI检查进行研究，网址为 基线，以及开始(在血清阳性受试者中)6周和12周后 积极的HAART治疗旨在降低脑脊液HIV-1RNA水平。衡量标准 脑白质信号改变，尾状核体积和任务相关 尾状核的血氧变化(在运动任务中) 与血清阳性者脑脊液中HIV-1RNA水平相关。这个 这些SMRI和fMRI方法在预测脑脊液病毒水平方面的作用将是 与行为指标相比，也可能与其他指标相比 单变量和多变量的非侵入性方法(如磁共振波谱) 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.