A Diffusion Tensor Imaging Study of HIV-Dementia

描述(由申请者提供)：这份K23申请书要求有一段职业发展时期，学习磁共振成像的先进方法，并利用这些方法来研究艾滋病毒-痴呆(HIV-D)。新兴的磁共振方法提供了使用其他成像技术无法获得的关于白质的微观结构信息。扩散张量成像(DTI)是一种非侵入性技术，可用于研究活体正常、病变或变性组织中白质的完整性。HIV-痴呆(HIV-D)以涉及白质的各种病理为特征。这项研究提供了一个机会来评估DTI在其他有意义的生物学和临床参数的背景下独一无二地揭示的信息。这项研究的对象将包括来自一项大型纵向队列研究HIV-D的特征良好的患者。从多年来的半年度评估中可以获得大量数据，包括来自血浆和脑脊液的生物标记物，以及关于神经认知和精神功能的信息。这项研究将确定使用DTI得出的脑白质完整性的微观结构指标是否与促进艾滋病毒感染的措施(例如病毒载量和免疫激活)、痴呆症的严重程度和特定的神经精神后遗症之间存在关系。此外，DTI的发现将在理论上感兴趣的生物标记物的背景下进行评估，包括选定的炎症指标(例如，肿瘤坏死因子)和内皮完整性(例如，基质金属蛋白酶-9)。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。在拟议的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.