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

• 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
• 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' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' 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

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.

项目摘要 MRI和组织病理学是对与年龄相关的认知障碍和痴呆症进行所有研究的两种关键方法，它们为疾病机制和治疗意义带来了关键的见解。一个主要的挑战是表征这两种方式的综合特性，这些属性在分辨率，覆盖范围和标记方面有所不同。此外，在体内，本质上很难在验尸检查中表征血管异常。验尸MRI已成为弥合差距的一种技术，但必要的技术仍未完全发展。在这项建议中，我们建议开发新颖的后MR成像方案和计算工具，以使多模式多模式多尺度大脑MR/组织病理学/蛋白质组学数据分析能够收集与认知障碍和痴呆症（VCID）有关的灰色和白质神经变性的理解。我们已经在拟议的研究的几个关键方面与领先的专家组装了一个多学科研究团队，以实现以下特定目标。 AIM 1：为人脑尸检，固定和阻塞/分段开发强大的，最先进的后验尸管道，以满足对AD/ADRD组合的MRI/组织病理学全面分析的需求。 These include (a) characterization of the effects of post-mortenem interval (PMI) and formalin fixation (i.e., Aim 2: Develop a multi-modality atlas and database of the human medial temporary 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包括AD，TBI相关的ADRC和其他ADRD的ADRC，重点是Aβ，TAU，血管和微结构病理学。验证后MRI和组织病理学的素图可以更好地理解小血管疾病的体内和体内发现（SVD）。 AIM 4：开发用于成像和病理学协议，软件工具和大脑图书馆的数字库，以及相关的验尸和后MRI和生物材料数据，将在研究界共享。总的来说，该项目将为开发标准化且可访问的MRI-Enstrology协议，新颖的后验尸和共同注册工具，以及来自75个基本上大脑的所有成像和生物材料数据的资源，以推动AD/ADRD中VCID病理学的研究。