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:
    8073460
  • 负责人:
  • 金额:
    $ 34.41万
  • 依托单位:
  • 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 2014-03-31
  • 项目状态:
    已结题

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):我们拟议研究的总体目标是建立NeuroAIDS的神经影像学标志物与人类免疫缺陷病毒(HIV-1)感染中枢神经系统(CNS)导致的神经病理过程之间的预测相关性。我们建议对HIV阳性个体捐赠的脑标本进行尸检,这些个体在放射学、临床和行为学上都有很好的特征,使用不同的神经成像方式在多个分辨率水平上进行检查。成像和神经病理学全脑数据之间的相关性将通过拓扑学计算,并通过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,并测量与皮质和皮质下灰质(GM)相关的形态测量参数。其次,将反映WM完整性的基于DTI的分数各向异性(FA)和平均扩散率(MD)图与MRI体积数据配准,以突出不同神经成像模式检测宏观WM变化的任何差异。这些地图也将被注册到新建立的DTI为基础的连接图集,确定主要的纤维束损害的病变,从而跟踪特定的功能网络受WM病理。我们将描述每种情况下,GM和WM HIV相关变化的相对贡献,以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,将产生直接与神经影像学数据相当的HIVE标志物(即病毒负荷,炎症,轴突完整性和皮质变性)的定量图。对于每个脑标本,将使用二维(2D)和三维(3D)常规结合进行神经病理学和成像数据的地形图配准,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,以比较特定的神经病理学和神经影像学标志物。对于每个受试者,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”的转换是理解成像证据的病理基础的关键,而成像证据在临床上对于神经学诊断和疾病预后是不可或缺的。公共卫生相关性:我们将进行,在一个很好的表征样品,由HIV感染引起的神经病理现象的多参数检查,相关的疾病标志物揭示了不同的成像方式(体内和体外)与特定的组织学方法定位。这项研究将提高我们对艾滋病毒神经发病机制的理解,通过非侵入性的神经体征和对治疗的反应尽早发现。

项目成果

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Jacopo Annese其他文献

Jacopo Annese的其他文献

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{{ truncateString('Jacopo Annese', 18)}}的其他基金

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
  • 财政年份:
    2009
  • 资助金额:
    $ 34.41万
  • 项目类别:
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:
    7933792
  • 财政年份:
    2009
  • 资助金额:
    $ 34.41万
  • 项目类别:
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:
    8264207
  • 财政年份:
    2009
  • 资助金额:
    $ 34.41万
  • 项目类别:
PROFILING OF CORTICAL AREAS BY MICRO-MRI
通过显微 MRI 分析皮质区域
  • 批准号:
    7956914
  • 财政年份:
    2009
  • 资助金额:
    $ 34.41万
  • 项目类别:
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:
    8442886
  • 财政年份:
    2009
  • 资助金额:
    $ 34.41万
  • 项目类别:
A Probabilistic Map of Human Visual Cortical Areas from Quantitative Microscopy
定量显微镜下人类视觉皮层区域的概率图
  • 批准号:
    8126313
  • 财政年份:
    2008
  • 资助金额:
    $ 34.41万
  • 项目类别:
A Probabilistic Map of Human Visual Cortical Areas from Quantitative Microscopy
定量显微镜下人类视觉皮层区域的概率图
  • 批准号:
    8311768
  • 财政年份:
    2008
  • 资助金额:
    $ 34.41万
  • 项目类别:
A Probabilistic Map of Human Visual Cortical Areas from Quantitative Microscopy
定量显微镜下人类视觉皮层区域的概率图
  • 批准号:
    7894622
  • 财政年份:
    2008
  • 资助金额:
    $ 34.41万
  • 项目类别:
PROFILING OF CORTICAL AREAS BY MICRO-MRI
通过显微 MRI 分析皮质区域
  • 批准号:
    7726197
  • 财政年份:
    2008
  • 资助金额:
    $ 34.41万
  • 项目类别:
A Probabilistic Map of Human Visual Cortical Areas from Quantitative Microscopy
定量显微镜下人类视觉皮层区域的概率图
  • 批准号:
    7661469
  • 财政年份:
    2008
  • 资助金额:
    $ 34.41万
  • 项目类别:
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