A Multiparametric MR Study of Early and Late Stage HIV Infection

描述（由申请人提供）：更清楚地了解早期HIV感染中脑损伤的风险因素对于合理干预和神经保护工作至关重要。定量磁共振（MR）成像方法可用于在不同分析级别生成大脑的客观测量结果。这项研究将利用这些非侵入性技术系统地量化感染早期HIV患者的脑损伤，以确定与神经系统进展风险增加相关的因素。本研究的重点是外周循环中活化的单核细胞和影响单核细胞运输的因素（血浆、CSF中的TNF α和MCP-1）。还将评价免疫学（CD 4+和CD 8+）和病毒学（血浆、CSF中的HIV RNA）因子。将在早期（血清转换后6个月内）和无症状HIV感染的HIV患者中评价神经系统进展的这些潜在决定因素与脑损伤和认知障碍客观测量的关系模式。将在基线和基线后2年的随访评估时对所有受试者进行评价。自动分割算法将用于推导标准化脑实质和特定组织类别（灰质、白色物质和CSF）的体积分数。扩散张量成像（DTI）将用于测量整个大脑和艾滋病毒患者易受损伤的特定区域（包括基底神经节和深层白色物质）的显微结构变化。还将使用定量MR方法询问骨髓。后一项成像研究的动机是骨髓中的免疫激活影响单核细胞向大脑的运输以及HIV复制，因此可能是神经损伤的关键决定因素。将检查体内骨髓测量与脑损伤和神经认知障碍的关系程度。将根据外周循环中活化单核细胞的水平以及单核细胞扩增和细胞过多的骨髓活检结果评价这些测量的组织学意义。测量大脑的磁共振技术将用于确定早期艾滋病毒感染是否会发生损伤。这些技术还将用于确定特定因素是否与艾滋病毒感染早期和无症状阶段的大脑变化有关。骨髓中发生的变化也将作为艾滋病毒患者脑损伤风险增加的指标进行研究。

DESCRIPTION (provided by applicant): A clearer understanding of risk factors for brain injury in early HIV infection is critical for rational intervention and neuroprotection efforts. Quantitative Magnetic Resonance (MR) Imaging methodologies can be used to generate objective measurements of the brain at different levels of analysis. This investigation will exploit these noninvasive technologies to systematically quantify brain injury in HIV patients in early stages of infection in order to identify factors associated with increased risk of neurological progression. The focus of this investigation concerns activated monocytes in the peripheral circulation and factors that influence monocyte trafficking (TNFa and MCP-1, in plasma, CSF). Immunologic (CD4+ and CD8+) and virologic (HIV RNA in plasma, CSF) factors will also be evaluated. These potential determinants of neurological progression will be evaluated for patterns of relationship to objective measurements of brain injury and cognitive impairment in HIV patients in early (within 6 months of seroconversion) and asymptomatic HIV infection. All subjects will be evaluated at baseline and at a follow-up assessment, two years post-baseline. Automated segmentation algorithms will be used to derive volume fractions of the normalized brain parenchyma and of specific tissue classes (gray matter, white matter and CSF). Diffusion Tensor Imaging (DTI) will be used to measure microstructural changes in the whole brain and in specific regions that are vulnerable to injury in HIV patients, including the basal ganglia and deep white matter. The bone marrow will also be interrogated with quantitative MR methodologies. The latter imaging studies are motivated by evidence that immune activation in the marrow influences monocyte trafficking to the brain, as well as HIV replication, and therefore may represent a critical determinant of neurological injury. The in vivo marrow measurements will be examined for the degree of relationship to brain injury and neurocognitive impairment. The histological significance of these measurements will be evaluated with respect to levels of activated monocytes in the peripheral circulation and marrow biopsy findings of monocyte expansion and hypercellularity. Magnetic Resonance techniques for measuring the brain will be used to determine if injury occurs in early HIV infection. These techniques will also be used to determine whether specific factors are associated with changes in the brain in early and asymptomatic stages of HIV infection. Changes occurring in the bone marrow will also be studied as indicators of increased risk of brain injury in HIV patients.