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标志物之间的预测性相关性。 神经艾滋病和由于中枢神经系统感染而发生的神经病理过程 人类免疫缺陷病毒(HIV-1)感染神经系统(CNS)。我们建议进行尸检 对放射学特征良好的艾滋病毒感染者捐赠的脑组织样本进行检查， 在临床上和行为上使用不同的神经成像方式在多个分辨率水平上。这个 成像和神经病理全脑数据之间的相关性将通过地形图和 与同一对象相关的互补数据集的配准；体内和体外。 高分辨率磁共振成像方案，应用于尸检，将被用来定位和分类白质(WM) 信号异常和测量与皮质和皮质下灰质相关的形态参数 (通用汽车)。其次，基于DTI的分数各向异性(FA)和平均扩散系数(MD)图，反映了WM的完整性 将被记录到MRI体积数据中，以突出在宏观检测中的任何差异 不同神经成像方式对WM的影响。这些地图也将注册到新建立的 基于DTI的连通性图谱，识别病变损害的主要纤维束，因此 追踪受西医病理影响的特定功能网络。我们将为每一种情况描述亲属的特征 GM和WM HIV相关变化对解释在捐赠者中观察到的神经行为特征的贡献。 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，将产生蜂巢标志物(即病毒负荷、炎症、轴突完整性、 和皮质退行性变)直接与神经成像数据相比较。对于每个大脑样本， 神经病理和成像数据的地形配准将使用2维(2D)和3维 三维(3D)例程相结合，以实现不同医疗模式之间的最佳相关性。 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和神经成像 记号笔。对于每个受试者，这些最终与所获得的相应扫描的特征有关 在活体内。这种“死后到活体”的转换是理解成像的病理基础的关键 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.