A Diffusion Tensor Imaging Study of HIV-Dementia

描述（由申请人提供）：此 K23 申请要求一段时间的职业发展，以研究磁共振 (MR) 成像的先进方法，并利用它们来研究 HIV-痴呆症 (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，可用于研究体内正常、患病或退化组织的白质完整性。 HIV-痴呆 (HIV-D) 的特点是涉及白质的各种病变。这项研究提供了一个机会，可以在其他有意义的生物学和临床参数的背景下评估 DTI 独特揭示的信息。这项调查的受试者将包括来自大型纵向队列研究 ef HIV-D 的特征明确的患者。多年来的半年评估提供了大量数据，包括来自血浆和脑脊液的生物标志物，以及有关神经认知和精神功能的信息。这项研究将确定使用 DTI 得出的白质完整性的微观结构测量是否与 HIV 感染进展的测量（例如病毒载量和免疫激活）、痴呆的严重程度和特定的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（例如 TNF）和内皮完整性（例如 MMP-9）的选择测量。这些发现将有助于了解 HIV-D 的发病机制，并可能提供有关其他中枢神经系统疾病的见解。在拟议奖项期间获得的经验将为进一步独立研究 HIV-D 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.