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

基本信息

批准号：
7933792
负责人：
Jacopo Annese
金额：
$ 36.01万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
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/7933792
关键词：
3-Dimensional AIDS neuropathy Affect Alzheimer&apos 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

项目摘要

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）：我们拟议的研究的总体目标是建立神经成像标记的神经成像标记与通过人类免疫缺陷病毒（HIV-1）感染而发生的神经成像标志物与神经发生过程之间的预测相关性。我们提出了由HIV+个体捐赠的大脑标本的死后检查，他们在放射线学上，临床和行为上使用不同的神经影像态在多个分辨率上使用不同的神经成像方式。成像与神经病理全脑数据之间的相关性将通过地形图进行计算，并通过相对于同一主题的互补数据集进行计算；体内和前体体。高分辨率MRI方案（应用后验尸）将用于定位和分类白质（WM）信号异常，并相对于皮质和皮层灰质（GM）测量形态计量参数。其次，基于DTI的分数各向异性（FA）和平均扩散率（MD）地图，反映WM完整性将注册到MRI体积数据中，以突出显示出不同神经成像模态的宏观WM变化时的任何差异。这些地图还将注册到新建立的基于DTI的连接性图像，识别病变损害的主要纤维道，从而追踪受WM病理影响的特定功能网络。对于每种情况，我们将表征GM和WM HIV相关的变化的相对贡献，以解释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，大型场显微镜和立体学，将产生与神经成像数据直接相当的蜂巢标记（即病毒负担，炎症，轴突完整性和皮质变性）的定量图（即病毒负担，炎症，轴突完整性和皮质变性）。对于每个大脑标本，将使用二维（2D）和3维（3D）例程进行神经病理学和成像数据的地形注册，以使不同模态之间的最佳相关性结合在一起。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学和神经影像学标记。对于每个主题，这些最终都与体内获得的相应扫描的特征有关。这种“体内验尸”翻译是理解成像证据的病理基础的关键，在临床上，对于神经系统诊断和疾病的预后是必不可少的。公共卫生相关性：我们将在表征良好的样本中进行神经发育现象的多参数检查，该检查是由HIV感染引起的，这将疾病的标志物与不同的影像学方式（体内和体内）与通过特定组织学方法局部的那些相关。这项研究将提高我们对通过非侵入性神经系统迹象和对治疗反应的最早检测HIV神经病发生的理解。