Multimodal Correlation of Imaging Markers and Neuropathogenesis of NeuroAIDS

影像学标志物与神经艾滋病神经发病机制的多模态相关性

• 批准号: 7622314
• 负责人: Jacopo Annese
• 金额: $ 37.54万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-17 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7622314
• 关键词: 3-Dimensional; AIDS neuropathy; Affect; Alzheimer' s Disease; Anatomy; Anisotropy; Anti-Retroviral Agents; Area; Atlases; Autopsy; Base Sequence; Brain; Brain Mapping; California; Central Nervous System Infections; Cerebral cortex; Cerebrum; Cessation of life; Characteristics; Clinical; Combined Modality Therapy; Computer Assisted; Conflict (Psychology); Contracts; Data; Data Set; Demyelinations; Detection; Diagnosis; Diagnostic; Diffusion; Disease; Disease Marker; Disease Progression; Dissociation; Doctor of Medicine; Early Diagnosis; Evaluation; Fiber; Formalin; Funding; Gliosis; Goals; Grant; HIV; HIV Infections; HIV encephalitis; HIV-1; Hand; Heterogeneity; Image; Imaging Techniques; Impairment; Individual; Infection; Inflammation; Inflammatory; Injury; Institution; Interest Group; Label; Lesion; Link; Location; Magnetic Resonance Imaging; Maps; Measures; Methods; Microscope; Microscopic; Microscopy; Modality; Modeling; Neuraxis; Neurocognitive; Neurocognitive Deficit; Neurodegenerative Disorders; Neurologic; Neuropathogenesis; PTPRC gene; Parkinson Disease; Participant; Pathogenesis; Pathologic; Pathology; Patients; Pattern; Persons; Pigments; Probability; Procedures; Process; Protocols documentation; Recording of previous events; Recruitment Activity; Relative (related person); Reporting; Research; Resolution; Sampling; Scanning; Scheme; Series; Severities; Signal Transduction; Site; Slide; Specimen; Staging; Staining method; Stains; Strabismus; Stroke; Sum; Surface; Techniques; Thick; Time; Tissues; Translating; Translations; Validation; Viral Load result; Viral Proteins; Wallerian Degeneration; advanced disease; astrogliosis; base; brain volume; cerebral atrophy; density; design; follow-up; gray matter; high risk; hippocampal pyramidal neuron; imaging modality; improved; in vivo; indexing; millimeter; neurobehavioral; neuroimaging; neuroinflammation; neuropathology; outcome forecast; public health relevance; research study; response; statistics; tool; two-dimensional; water diffusion; white matter; white matter change; white matter damage

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.

描述（由申请人提供）：我们提出的研究的总体目标是建立 NeuroAIDS 的神经影像学标记物与人类免疫缺陷病毒（HIV-1）感染中枢神经系统（CNS）而发生的神经病理过程之间的预测相关性。我们建议对 HIV+ 个体捐赠的大脑标本进行尸检，这些标本已使用不同的神经影像模式在多个分辨率水平上进行了放射学、临床和行为方面的详细表征。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并通过相对于同一受试者的互补数据集的注册来计算；体内和离体。尸检后应用的高分辨率 MRI 协议将用于定位和分类白质 (WM) 信号异常，并测量相对于皮质和皮质下灰质 (GM) 的形态参数。其次，反映 WM 完整性的基于 DTI 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，以突出不同神经影像模式检测宏观 WM 变化时的任何差异。这些图谱还将被注册到新建立的基于 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。我们将对每个病例​​描述 GM 和 WM HIV 相关变化的相对贡献，以解释在捐赠者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，将产生与神经影像数据直接可比的 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。对于每个脑样本，将使用二维 (2D) 和三维 (3D) 例程进行神经病理学和成像数据的地形配准，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来比较特定的神经病理学和神经影像标记。对于每个受试者来说，这些最终与体内获得的相应扫描的特征相关。这种“死后到体内”的翻译是理解影像学证据的病理基础的关键，这对于临床上的神经学诊断和疾病的预后是必不可少的。公共健康相关性：我们将在特征明确的样本中对 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（体内和离体）揭示的疾病标志物与特定组织学方法定位的标志物相关联。该研究将提高我们对艾滋病毒神经发病机制的理解，以便通过神经体征和治疗反应的非侵入性手段尽早检测到。