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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：
JAMES C GEE
金额：
$ 168.88万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
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：
https://reporter.nih.gov/project-details/10812034
关键词：
3-Dimensional Access to Information Age-associated memory impairment Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Alzheimer&apos s disease related dementia Amyloid beta-Protein Atlases Autopsy Axon Biocompatible Materials Blood Vessels Brain Brain region Clinical Pathology Cognitive Collection Communities Comprehension Data Data Analyses Databases Dementia Demyelinations Diagnosis Diffusion Digital Libraries Disease Disease Marker Elderly Ensure Formalin Geometry Health Hemorrhage Heterogeneity Hippocampus Histologic Histology Histopathology Hour Human Image Image Analysis Imaging Techniques Interdisciplinary Study Knowledge Link Machine Learning Magnetic Resonance Imaging Maps Medial Methods Microvascular Dysfunction Modality Modeling Molecular Multimodal Imaging Nature Nerve Degeneration Neurology Neurons Pathogenicity Pathologic Pathology Pathway interactions Predisposition Prefrontal Cortex Procedures Property Proteomics Protocols documentation Research Resolution Resources Sampling Signal Transduction Site Software Tools Specimen Stains Standardization Structure TBI Patients Techniques Temporal Lobe Therapeutic Therapeutic Intervention Tissues White Matter Hyperintensity brain tissue cellular pathology cohort computerized tools deep learning density gray matter hemodynamics histopathological examination image archival system image processing image registration in vivo individual patient insight magnetic resonance imaging biomarker multimodality multiscale data neuropathology neurovascular novel open source response sample fixation shared repository tau Proteins tissue fixing tool tractography vascular abnormality vascular cognitive impairment and dementia white 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