Multimodal Correlation of Imaging Markers and Neuropathogenesis of NeuroAIDS

摘要 我们提出的研究的总体目标是建立神经影像学标记物之间的预测相关性 神经艾滋病和神经病理过程，发生作为中央感染的结果， 人类免疫缺陷病毒（HIV-1）对神经系统（CNS）的影响。我们建议验尸 检查由艾滋病毒阳性个体捐赠的脑标本，这些个体在放射学上具有良好的特征， 临床上和行为上使用不同的神经成像模式在多个分辨率水平。的 成像和神经病理学全脑数据之间的相关性将通过地形图和 相对于同一受试者的互补数据集的配准;体内和体外。 死后应用高分辨率MRI方案，将用于定位和分类白色物质（WM） 信号异常和测量相对于皮质和皮质下灰质的形态测量参数 （GM）。其次，基于DTI的分数各向异性（FA）和平均扩散率（MD）图，反映WM完整性 将配准到MRI体积数据中，以突出显示肉眼检测中的任何差异 WM的变化通过不同的神经影像学方式。这些地图也将登记到新成立的 基于DTI的连通性图谱，识别受病变损害的主要纤维束， 追踪受WM病理影响的特定功能网络。我们将为每一种情况下的特点相对 GM和WM HIV相关变化的贡献来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、大视野显微镜和 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）与神经成像数据直接可比。对于每个大脑样本， 将使用二维（2D）和三维（3D）技术进行神经病理学和成像数据的地形图配准。 三维（3D）例程组合用于不同模态之间的最佳相关性。 这个项目建立了一个独特的分析背景，以比较特定的神经病理学和神经影像学 标记。对于每个受试者，这些最终与所获取的相应扫描的特征相关 in vivo.这种“死后到体内”的转换是理解成像病理基础的关键 临床上对神经学诊断和疾病预后不可或缺的证据。

ABSTRACT 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.