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感染脑损伤的危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水平上生成大脑的客观测量。这项研究将利用这些非侵入性技术系统地量化早期感染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（血浆和CSF中的TNFa和MCP-1）。免疫学（CD4+和CD8+）和病毒学（血浆、脑脊液中的HIV RNA）因素也将进行评估。这些神经系统进展的潜在决定因素将被评估与早期（血清转化后6个月内）和无症状HIV感染的HIV患者脑损伤和认知障碍的客观测量的关系模式。所有受试者将在基线时进行评估，并在基线后两年进行随访评估。自动分割算法将用于获得规范化脑实质和特定组织类别（灰质，白质和脑脊液）的体积分数。弥散张量成像（DTI）将用于测量整个大脑的微观结构变化，以及艾滋病毒患者易受损伤的特定区域，包括基底神经节和深部白质。骨髓也将被定量磁共振方法询问。后一项影像学研究的动机是有证据表明，骨髓中的免疫激活影响单核细胞向大脑的运输，以及艾滋病毒的复制，因此可能是神经损伤的关键决定因素。体内骨髓测量将被检查与脑损伤和神经认知障碍的关系程度。这些测量的组织学意义将根据外周循环中活化单核细胞的水平和单核细胞扩增和高细胞性的骨髓活检结果进行评估。用于测量大脑的磁共振技术将用于确定早期HIV感染是否发生损伤。这些技术还将用于确定HIV感染早期和无症状阶段的大脑变化是否与特定因素有关。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.