A Multiparametric MR Study of Early and Late Stage HIV Infection

早期和晚期 HIV 感染的多参数 MR 研究

• 批准号: 7422795
• 负责人: ANN B RAGIN
• 金额: $ 35.35万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-29 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7422795
• 关键词: Acute; Algorithms; Basal Ganglia; Biological Response Modifiers; Biopsy; Blood Circulation; Bone Marrow; Brain; Brain Injuries; CCL2 gene; CD4 Lymphocyte Count; CD8B1 gene; Cause of Death; Cells; Class; Depth; Diffusion Magnetic Resonance Imaging; Disease Progression; Evolution; FCGR3B gene; Genetic Polymorphism; HIV; Highly Active Antiretroviral Therapy; Image; Immune; Immune response; Immune system; Immunologics; Impaired cognition; Impairment; Individual; Infection; Inflammatory Response; Injury; Integration Host Factors; Intervention; Investigation; Magnetic Resonance; Magnetic Resonance Imaging; Marrow; Measurement; Measures; Methodology; Morbidity - disease rate; Nervous System Trauma; Neurocognitive; Neurologic; Neurological outcome; Neuropathogenesis; Numbers; Patients; Pattern; Peripheral; Plasma; Production; Risk; Risk Factors; Role; Severities; Staging; Systemic disease; TNF gene; Techniques; Technology; Tissues; Ursidae Family; Viral; Viral Load result; Virus; Virus Diseases; Virus Replication; Week; brain tissue; day; follow-up; gray matter; in vivo; monocyte; neuroprotection; prognostic; theories; trafficking; viral RNA; white matter

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.

描述（由申请人提供）：对早期艾滋病毒感染中脑损伤的危险因素的更清晰理解对于理性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的不同水平下生成大脑的客观测量。这项研究将利用这些非侵入性技术来系统地量化感染早期艾滋病毒患者的脑损伤，以识别与神经系统进展风险增加有关的因素。这项研究的重点涉及周围循环中激活的单核细胞以及影响单核细胞运输的因素（TNFA和MCP-1，等离子体，CSF）。还将评估免疫学（CD4+和CD8+）和病毒学（血浆中的HIV RNA，CSF）因子。这些潜在的神经进展的决定因素将评估与艾滋病毒患者在早期（血清转化后6个月内）和无症状HIV感染的脑损伤和认知障碍的关系模式。所有受试者将在基线和后续评估中进行评估，即基线后两年。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CSF）的体积分数。扩散张量成像（DTI）将用于测量整个大脑以及容易受到HIV患者损伤的特定区域的微观结构变化，包括基底神经节和深白质。骨髓还将通过定量MR方法进行询问。后者的成像研究是出于证据表明骨髓中的免疫激活会影响大脑的单核细胞运输以及HIV复制，因此可能代表神经系统损伤的关键决定因素。将检查体内骨髓测量值与脑损伤和神经认知障碍的关系程度。这些测量值的组织学意义将与单核细胞扩张和超细胞性的外周循环和骨髓活检结果相对于活化单核细胞的水平进行评估。用于测量大脑的磁共振技术将用于确定早期HIV感染中是否发生损伤。这些技术还将用于确定特定因素是否与艾滋病毒感染的早期和无症状阶段的大脑变化有关。还将研究骨髓中发生的变化，作为增加HIV患者脑损伤风险的指标。