A Diffusion Tensor Imaging Study of HIV-Dementia

描述（由申请人提供）：此K23申请要求一段职业发展时期，研究磁共振（MR）成像的先进方法，并利用它们研究hiv -痴呆（HIV-D）。新兴的MR方法提供了其他成像技术无法获得的有关白质的微结构信息。弥散张量成像（DTI）是一种非侵入性技术，可用于研究体内正常、病变或变性组织的白质完整性。hiv -痴呆（HIV-D）以涉及白质的各种病理为特征。这项研究为评估DTI在其他有意义的生物学和临床参数背景下独特揭示的信息提供了机会。本研究的对象将包括来自HIV-D大型纵向队列研究的特征明确的患者。从多年来的半年度评估中可以获得大量数据，包括从血浆和脑脊液中提取的生物标志物，以及有关神经认知和精神功能的信息。本研究将确定使用DTI得出的白质完整性微结构测量是否与HIV感染进展（如病毒载量和免疫激活）、痴呆严重程度和特定神经精神后遗症有关。此外，DTI结果将在具有理论意义的生物标志物的背景下进行评估，包括炎症（如TNF）和内皮完整性（如MMP-9）的选择测量。这些发现将有助于理解HIV-D的发病机制，并可能为其他中枢神经系统疾病提供见解。在拟议奖励期间获得的经验将为进一步独立研究HIV-D的神经生物学因素奠定基础。

DESCRIPTION (provided by applicant): This K23 application requests a period of career development to study advanced methods in Magnetic Resonance (MR) imaging and exploit them to study HIV-Dementia (HIV-D). Emerging MR methods provide microstructural information concerning white matter that cannot be obtained using other imaging techniques. Diffusion Tensor Imaging (DTI) is a non-invasive technique that may be useful in studying white matter integrity in normal, diseased or degenerating tissue in vivo. HIV-Dementia (HIV-D) is characterized by various pathologies involving white matter. This study represents an opportunity to evaluate information uniquely revealed by DTI in the context of other meaningful biological and clinical parameters. Subjects in this investigation will include well-characterized patients from a large, longitudinal cohort study_ef HIV-D. Extensive data is available from semi-annual evaluations over a number of years, including biological markers derived from plasma and CSF, as well as information concerning neurocognitive and psychiatric functioning. This study will determine whether microstructural measures of white matter integrity, derived using DTI, bear a relation to measures of advancing HIV infection (e.g. viral load and immune activation), severity of dementia and specific neuropsychiatric sequelae. In addition, the DTI findings will be evaluated in the context of biological markers of theoretical interest, including select measures of inflammation (e.g. TNF ) and endothelial integrity (e.g. MMP-9). These findings will contribute to an understanding of the pathogenesis of HIV-D and may provide insights concerning other CNS disorders. Experience gained during the proposed award will lay the foundation for further independent investigations of neurobiological factors in HIV-D.