Multi-scale and multi-modality imaging of neuropathology in VCID
VCID 神经病理学的多尺度、多模态成像
基本信息
- 批准号:10812034
- 负责人:
- 金额:$ 168.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-22 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAccess to InformationAge-associated memory impairmentAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAlzheimer&aposs disease related dementiaAmyloid beta-ProteinAtlasesAutopsyAxonBiocompatible MaterialsBlood VesselsBrainBrain regionClinical PathologyCognitiveCollectionCommunitiesComprehensionDataData AnalysesDatabasesDementiaDemyelinationsDiagnosisDiffusionDigital LibrariesDiseaseDisease MarkerElderlyEnsureFormalinGeometryHealthHemorrhageHeterogeneityHippocampusHistologicHistologyHistopathologyHourHumanImageImage AnalysisImaging TechniquesInterdisciplinary StudyKnowledgeLinkMachine LearningMagnetic Resonance ImagingMapsMedialMethodsMicrovascular DysfunctionModalityModelingMolecularMultimodal ImagingNatureNerve DegenerationNeurologyNeuronsPathogenicityPathologicPathologyPathway interactionsPredispositionPrefrontal CortexProceduresPropertyProteomicsProtocols documentationResearchResolutionResourcesSamplingSignal TransductionSiteSoftware ToolsSpecimenStainsStandardizationStructureTBI PatientsTechniquesTemporal LobeTherapeuticTherapeutic InterventionTissuesWhite Matter Hyperintensitybrain tissuecellular pathologycohortcomputerized toolsdeep learningdensitygray matterhemodynamicshistopathological examinationimage archival systemimage processingimage registrationin vivoindividual patientinsightmagnetic resonance imaging biomarkermultimodalitymultiscale dataneuropathologyneurovascularnovelopen sourceresponsesample fixationshared repositorytau Proteinstissue fixingtooltractographyvascular abnormalityvascular cognitive impairment and dementiawhite matter
项目摘要
PROJECT SUMMARY
MRI and histopathology are two key methods for all research into age-related cognitive impairment and dementia and they have brought key insights into disease mechanisms and therapeutic implications. A major challenge is to characterize the integrative properties of these two modalities, which differ in resolution, coverage, and markers; furthermore, in vivo, vascular abnormalities by nature are difficult to be characterized on post-mortem exams. Post-mortem MRI has emerged as a technique to bridge the gap but necessary techniques are still not fully developed. In this proposal, we propose to develop novel post-mortem MR imaging protocols and computational tools to enable the collection of multi-modal multi-scale brain MR/histopathology/ proteomics data analysis to advance our understanding of gray and white matter neurodegeneration associated with vascular contributions to cognitive impairment and dementia (VCID). We have assembled a multi-disciplinary research team with leading experts in several key aspects of the proposed study to achieve the following specific aims. Aim 1: Develop a robust, state-of-the-art post-mortem pipeline for human brain autopsy, fixation, and blocking/sectioning that meet the need for combined MRI/histopathology full-scale analysis of AD/ADRD. These include (a) characterization of the effects of post-mortem interval (PMI) and formalin fixation (i.e., hours to weeks) for modeling such effect in both spatial and temporal domains; and (b) establishing standardized ex vivo MRI procedures that focus on streamlining fixation and sectioning protocols to minimize imaging and tissue deformation/degradation, enabling dependable co-registration between imaging procedures and ensuring precise top-down correlation with histopathology and proteomic analysis. Aim 2: Develop a multi-modality atlas and database of the human medial temporal lobe (MTL) and prefrontal cortex (PFC) pathology based on co-registered multimodal and multiscale MRI and neuropathology data from a well-characterized cohort at NYU Langone Health ADRC that includes AD, TBI-related and other ADRD vs control subjects, focusing on Aβ, Tau, vascular, and microstructural pathology. The multi-modality vascular and microstructural atlases will be reconstructed and integrated with vascular pathology staining. Aim 3: Study white matter hyperintensities (WMHs) by performing high-fidelity and multi-contrast voxel-wise mapping of post-mortem MRI and histopathology that enable a better understanding of in vivo and ex vivo findings of small vessel disease (SVD). This aim tackles two major obstacles in the research of SVD associated with VCID: cross-modality interpretation and heterogeneity of WMHs. Aim 4: Develop digital libraries for imaging and pathology protocols, software tools, and brain atlases, as well as relevant pre- and post-mortem MRI and biomaterial data to be shared in the research community. Collectively, this project will make contributions to develop standardized and accessible MRI- histology protocols, novel post-mortem and co-registration tools, as well as resources of all imaging and biomaterial data from 75 elderly brains to advance the study of VCID pathology in AD/ADRD.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JAMES C GEE其他文献
JAMES C GEE的其他文献
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