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：
Jacopo Annese
金额：
$ 34.41万
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 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8073460
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 Health 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 United States National Institutes of Health 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 research study response statistics tool two-dimensional water diffusion white matter white matter change white matter damage

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 Health 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 United States National Institutes of Health 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 research study response statistics tool two-dimensional water diffusion white matter white matter change white matter damage

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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.