An Automated platform for 3D reconstruction and profiling of post-mortem Alzheimer's Disease brains

用于对死后阿尔茨海默病大脑进行 3D 重建和分析的自动化平台

• 批准号: 10395363
• 负责人: Timothy M. Ragan
• 金额: $ 47.88万
• 依托单位: TISSUEVISION, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10395363
• 关键词: 3-Dimensional; Address; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease model; Anatomy; Antibodies; Area; Automobile Driving; Autopsy; Back; Basic Science; Biology; Brain; Cardiac; Cells; Characteristics; Client; Clinical; Collaborations; Communicable Diseases; Communities; Complex; Computer software; Data; Databases; Dementia; Densitometry; Discipline; Disease; Dyes; Elderly; Exposure to; Face; Fee-for-Service Plans; Feedback; Funding; Goals; Histologic; Histology; Human; Image; Indiana; Liver Fibrosis; Magnetic Resonance Imaging; Maps; Mechanics; Microscopic; Microscopy; Microtomy; Molecular; Molecular Analysis; Molecular Profiling; Mus; Neurodegenerative Disorders; Neurons; Neurosciences; Neurosciences Research; Organ; Pathologic; Pathology; Pattern; Phase; Production; Pulmonology; Rattus; Research; Research Contracts; Research Personnel; Resolution; Rodent; Sampling; Section 8; Services; Slice; Slide; Small Business Innovation Research Grant; Specimen; Stains; System; Techniques; Technology; Thick; Three-Dimensional Image; Tissue Model; Tissues; Universities; Validation; Visualization software; Work; anticancer research; base; brain tissue; clinical application; design; follow-up; human tissue; image registration; imaging platform; imaging system; indexing; mouse model; neural circuit; novel; particle; professor; reconstruction; respiratory; secondary analysis; terabyte; three-dimensional modeling; whole slide imaging; 3-Dimensional; Address; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease model; Anatomy; Antibodies; Area; Automobile Driving; Autopsy; Back; Basic Science; Biology; Brain; Cardiac; Cells; Characteristics; Client; Clinical; Collaborations; Communicable Diseases; Communities; Complex; Computer software; Data; Databases; Dementia; Densitometry; Discipline; Disease; Dyes; Elderly; Exposure to; Face; Fee-for-Service Plans; Feedback; Funding; Goals; Histologic; Histology; Human; Image; Indiana; Liver Fibrosis; Magnetic Resonance Imaging; Maps; Mechanics; Microscopic; Microscopy; Microtomy; Molecular; Molecular Analysis; Molecular Profiling; Mus; Neurodegenerative Disorders; Neurons; Neurosciences; Neurosciences Research; Organ; Pathologic; Pathology; Pattern; Phase; Production; Pulmonology; Rattus; Research; Research Contracts; Research Personnel; Resolution; Rodent; Sampling; Section 8; Services; Slice; Slide; Small Business Innovation Research Grant; Specimen; Stains; System; Techniques; Technology; Thick; Three-Dimensional Image; Tissue Model; Tissues; Universities; Validation; Visualization software; Work; anticancer research; base; brain tissue; clinical application; design; follow-up; human tissue; image registration; imaging platform; imaging system; indexing; mouse model; neural circuit; novel; particle; professor; reconstruction; respiratory; secondary analysis; terabyte; three-dimensional modeling; whole slide imaging

PROJECT SUMMARY AD is a complex, progressive neurodegenerative disease and is the most common cause of dementia among the elderly. It has a clear spatial and temporal progression; multiple lines of evidence show that the degeneration patterns seen in AD are not random but show a characteristic anatomical sequence as the pathology advances over decades. The mechanisms that cause these spatial patterns are poorly understood and basic questions about the relative contributions of microscopic molecular mechanisms versus macroscopic anatomical changes in driving AD progression remain unclear. Unfortunately, whole brain techniques like MRI lacks the necessary molecular contrast and resolution to answer these questions. Histology can reveal the microscopic, molecular signatures, but is constrained to small 2D sections due to technical limitations with large scale histology, particularly 3D histology. These limitations make it difficult to map AD progression and limit the usefulness of post-mortem tissue that might reveal crucial clues about AD. In this proposal we will address this barrier by providing a fee-for-service sectioning, slice mounting, staining, and imaging platform that will offer non-specialized labs the ability to obtain high quality 3D serial section reconstructions of post-mortem human brains up to entire hemispheres. Specimens can be sent to TissueVision where they will be sectioned at thicknesses ranging from 50 microns to 2 mm, with alternating block face imaging between sections to help facilitate 3D reconstruction. Each mounted section is available for further staining and digitization at high resolution with Whole Slide imaging (WSI) and served over the cloud to the client with optional 3D modeling. The physical sections can be returned to the client or stored for further follow-up analyses. This proposal combines expertise in microscopy and 3D histology at TissueVision with world- class clinical researchers at Indiana University and builds on existing work at TissueVision. The section capture and slide mounting is based on existing technology contained within our TissueCyte 1600FC STPT platform for mouse and rat brains. We also build on a strong collaboration with Jackson Labs and the MODEL-AD center with an existing TissueVision Phase II NIA SBIR to map AD spatial progression in mouse model brains. We will extend the collaboration to clinical collaborators at the Model-AD at Indiana University who will be supplying post-mortem human tissue and providing guidance and feedback on the histological quality. While our focus is on AD in this project, the proposed technology will have broad impact across a wide range of disciplines, from cardiac biology, infectious diseases, cancer, and basic research.

项目摘要 AD是一种复杂的，进行性的神经退行性疾病，是 老年人中的痴呆症。它具有清晰的空间和时间进展。多行 证据表明，AD中看到的变性模式不​​是随机的，而是显示 随着病理的发展，特征性解剖学序列数十年来。机制 这导致这些空间模式的理解很少，并且有关亲戚的基本问题 微观分子机制与宏观解剖学变化的贡献 驾驶广告进展尚不清楚。 不幸的是，像MRI这样的整个大脑技术都缺乏必要的分子对比度和 解决这些问题的决议。组织学可以揭示微观的分子 签名，但由于大规模的技术限制而被限制在小型2D部分 组织学，特别是3D组织学。这些限制使得映射广告进度很难 并限制可能揭示有关AD关键线索的事后组织的有用性。 在此提案中，我们将通过提供费用的服务部门来解决此障碍，切片 安装，染色和成像平台将提供非专业实验室的能力 获得高质量的3D串行部分重建，直到整个人类大脑 半球。可以将标本发送到Tissuevision，在厚度将其切成薄片 从50微米到2毫米不等，部分之间的交替块面成像以帮助 促进3D重建。每个安装的部分可用于进一步染色， 高分辨率的数字化，全幻灯片成像（WSI），并在云上送达 可选3D建模的客户。物理部分可以返回客户端或存储 进行进一步的后续分析。 该建议结合了显微镜和3D组织学方面的专业知识与世界 - 印第安纳大学的班级临床研究人员并以Tissuevision的现有工作为基础。这 截面捕获和幻灯片安装是基于我们中包含的现有技术 Tissuecyte 1600FC STPT平台用于小鼠和大鼠大脑。我们也建立一个强大的 与Jackson Labs和Model-AD中心合作与现有的Tissuevision阶段 II NIA SBIR以绘制小鼠模型大脑中的AD空间进程。我们将扩展 与印第安纳大学模型AD的临床合作者合作 提供验尸后人体组织，并提供有关组织学的指导和反馈 质量。尽管我们的重点是该项目的广告，但拟议的技术将产生广泛的影响 从心脏生物学，传染病，癌症和基本的广泛学科中 研究。