Multimodal Correlation of Imaging Markers and Neuropathogenesis of NeuroAIDS

描述（由申请人提供）：我们提出的研究的总体目标是建立神经艾滋病的神经影像学标志物与由于人类免疫缺陷病毒（HIV-1）感染中枢神经系统（CNS）而发生的神经发病过程之间的预测相关性。我们建议对HIV阳性个体捐献的脑标本进行死后检查，这些标本在放射学、临床和行为上都有很好的特征，使用不同的神经成像方式，在多个分辨率水平上。成像和神经病理全脑数据之间的相关性将通过地形计算和相对于同一主题的互补数据集的注册；体内和体外。在死后应用高分辨率MRI协议，将用于定位和分类白质（WM）信号异常，并测量相对于皮层和皮层下灰质（GM）的形态测量参数。其次，基于dti的反映WM完整性的分数各向异性（FA）和平均扩散率（MD）图将被注册到MRI体积数据中，以突出不同神经成像方式检测宏观WM变化的任何差异。这些图谱也将被记录到新建立的基于dti的连接图谱中，识别受病变损害的主要纤维束，从而追踪受WM病理影响的特定功能网络。我们将描述每种情况下GM和WM hiv相关变化的相对贡献，以解释在供体中观察到的神经行为特征。随后的全脑组织病理学方案，使用计算机辅助，大视场显微镜和体视学，将产生HIVE标记物（即病毒负荷，炎症，轴突完整性和皮质变性）的定量图，直接与神经成像数据相比较。对于每个脑标本，神经病理和成像数据的地形配准将使用二维（2D）和三维（3D）例程相结合，以实现不同模式之间的最佳相关性。该项目建立了一个独特的分析背景，以比较特定的神经病理和神经影像学标记。这些是，对于每个受试者，最终与体内获得的相应扫描的特征相关。这种“死后到体内”的转换是理解影像学证据病理基础的关键，对疾病的神经学诊断和预后是临床不可缺少的。公共卫生相关性：我们将在一个特征良好的样本中，对由HIV感染引起的神经发病现象进行多参数检查，将不同成像方式（体内和体外）显示的疾病标志物与特定组织学方法定位的标志物相关联。这项研究将提高我们对HIV神经发病机制的理解，从而通过非侵入性手段尽早发现神经症状和对治疗的反应。

DESCRIPTION (provided by applicant): The overall goal of our proposed study is to establish the predictive correlation between neuroimaging markers of NeuroAIDS and the neuropathogenetic processes that occur as a result of the infection of the Central Nervous System (CNS) by the Human Immunodeficiency Virus (HIV-1). We propose the postmortem examination of brain specimens donated by HIV+ individuals who have been well-characterized radiologically, clinically, and behaviorally using different neuroimaging modalities at multiple levels of resolution. The correlation between imaging and neuropathological whole-brain data will be computed topographically and via the registration of complementary data sets relative to the same subject; in vivo and ex vivo. High-resolution MRI protocols, applied postmortem, will be used to localize and classify White Matter (WM) signal abnormalities and to measure morphometric parameters relative to cortical and subcortical Grey Matter (GM). Secondly, DTI-based Fractional Anisotropy (FA) and Mean Diffusivity (MD) maps, reflecting WM integrity will be registered to MRI volumetric data in order to highlight any discrepancy in the detection of macroscopic WM changes by different neuroimaging modalities. These maps will also be registered to newly-established DTI-based atlases of connectivity, identifying major fiber tracts that are compromised by the lesions, and thus tracing specific functional networks affected by WM pathology. We shall characterize for each case the relative contribution of GM and WM HIV-related changes to explain neurobehavioral profiles observed in the donor. Subsequent whole-brain histopathological protocols, using computer-aided, large-field microscopy and stereology, will produce quantitative maps of HIVE markers (i.e. viral burden, inflammation, axonal integrity, and cortical degeneration) directly comparable to neuroimaging data. For each brain specimen, the topographic registration of neuropathological and imaging data will be done using 2-dimensional (2D) and 3- dimensional (3D) routines combined for the optimal correlation between different modalities. This project establishes a unique context of analysis to compare specific neuropathological and neuroimaging markers. These are, for each subject, ultimately related to the characteristics of corresponding scans acquired in vivo. This `postmortem to in vivo' translation is the key to understanding the pathological basis of the imaging evidence that is clinically indispensable for the neurological diagnosis and the prognosis of the disease. PUBLIC HEALTH RELEVANCE: We will conduct, in a well characterized sample, a multi-parametric examination of neuropathogenetic phenomena that are induced by HIV infection, correlating markers of the disease revealed by different imaging modalities (in vivo and ex vivo) with those localized by specific histological methods. The study will improve our understanding of HIV neuropathogenesis towards the earliest detection by non-invasive means of neurological signs and response to treatment.