A Multiparametric MR Study of Early and Late Stage HIV Infection

描述(由申请人提供)：更清楚地了解艾滋病毒感染早期脑损伤的风险因素对于合理的干预和神经保护努力至关重要。定量磁共振(MR)成像方法可以用来在不同的分析水平上产生对大脑的客观测量。这项研究将利用这些非侵入性技术，系统地量化感染早期艾滋病毒患者的脑损伤，以确定与神经进展风险增加相关的因素。这项研究的重点是外周循环中激活的单核细胞以及影响单核细胞转运的因素(血浆、脑脊液中的TNFa和MCP-1)。免疫学(CD4和CD8)和病毒学(血浆和脑脊液中的HIV RNA)因素也将被评估。这些神经进展的潜在决定因素将被评估与艾滋病毒患者早期(血清转换后6个月内)和无症状艾滋病毒感染的脑损伤和认知障碍的客观测量的关系模式。所有受试者都将在基线和基线后两年的后续评估中进行评估。自动分割算法将用于得出归一化脑实质和特定组织类别(灰质、白质和脑脊液)的体积分数。扩散张量成像(DTI)将被用来测量整个大脑以及艾滋病毒患者易受损伤的特定区域的微观结构变化，包括基底节和深层白质。骨髓也将用定量磁共振方法进行询问。后一种成像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激活的单核细胞水平和骨髓活检发现的单核细胞扩张和高细胞数来评估。测量大脑的磁共振技术将被用来确定在早期艾滋病毒感染时是否发生了损伤。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.