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记物之间的预测相关性 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) 影响神经系统 (CNS)。我们建议进行尸检 对艾滋病病毒感染者捐赠的脑标本进行检查，这些标本已经过放射学表征， 在临床和行为上使用不同分辨率的神经影像模式。的 成像和神经病理学全脑数据之间的相关性将通过地形计算 与同一主题相关的补充数据集的注册；体内和离体。 尸检中应用的高分辨率 MRI 协议将用于白质 (WM) 的定位和分类 信号异常并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) 和平均扩散率 (MD) 图，反映 WM 完整性 将被注册到 MRI 体积数据，以突出宏观检测中的任何差异 WM 因不同的神经影像学方式而变化。这些地图也将被注册到新成立的 基于 DTI 的连接图集，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。我们将针对每种情况描述相关的特征 GM 和 WM HIV 相关变化对解释在供体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、大视场显微镜和 体视学，将产生 HIVE 标记的定量图（即病毒负荷、炎症、轴突完整性、 和皮质变性）可直接与神经影像数据进行比较。对于每个大脑样本， 神经病理学和成像数据的地形配准将使用 2 维 (2D) 和 3-维 结合维度（3D）例程以实现不同模态之间的最佳相关性。 该项目建立了一个独特的分析背景来比较特定的神经病理学和神经影像学 标记。对于每个受试者来说，这些最终与所获取的相应扫描的特征相关 体内。这种“死后到体内”的翻译是理解成像病理基础的关键 临床上对于疾病的神经学诊断和预后不可缺少的证据。

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.