FMRI INDICES & CSF VIRAL LOAD IN HIV-INFECTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。据报道，脑脊液HIV-1 RNA的高水平以及相关的神经行为缺陷与血清病毒水平无关（Ellis et al., 2000; Ellis et al., 1997; marthur et al., 1997; Staprans et al., 1999; Wong et al., 1997）。这意味着，连续腰椎穿刺虽然是侵入性的，但可能是监测hiv相关神经退行性过程进展的最佳方法。需要灵敏的非侵入性方法来检测和监测艾滋病毒相关的中枢神经系统效应。本研究的目的是评估结构（SMRI）和功能（FMRI）成像方法在预测中枢神经系统病毒复制方面的应用。先前的研究表明，纹状体神经变性和弥散性脑白质损伤是这一人群中最一致的两种结构异常（Jernigan et al., 1993; Stout et al., 1998），精神运动减慢是最突出的功能缺陷。由于CSF HIV-1 RNA是目前可用的最佳中枢神经系统病毒复制指标，因此该指标将是拟议研究的主要因变量。神经行为受损和未受损的血清阳性个体组，以及血清阴性对照，将在基线和（血清阳性受试者）开始积极的HAART治疗后6周和12周进行重复sMRI/fMRI检查，旨在降低CSF HIV-1 RNA水平。白质信号变化、尾状核体积和尾状核血氧的任务相关变化（运动任务期间）的测量将与血清阳性受试者的CSF HIV-1 RNA水平相关。在单变量和多变量预测模型中，这些SMRI和FMRI测量在预测脑脊液病毒水平方面的效用将与行为测量的效用进行比较，并可能与其他非侵入性方法（如磁共振光谱）的效用进行比较。

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.