High-content light sheet microscopy of cleared tissue for mental health research

用于心理健康研究的透明组织的高内涵光片显微镜

• 批准号: 10282021
• 负责人: Samouil Farhi
• 金额: $ 32.76万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10282021
• 关键词: Address; Anatomy; Automation; Biological Models; Brain; Brain imaging; Catalogs; Communities; Custom; Engineering; Evaluation; Goals; Imaging technology; Institutes; Investigation; Label; Light; Lighting; Location; Mental Health; Microscope; Microscopy; Molecular Genetics; Mus; Neurobiology; Optics; Pattern; Performance; Photobleaching; Publishing; Research; Research Personnel; Role; Sampling; Scanning; Technology; Thick; Tissues; Work; brain tissue; cell type; cost; experience; experimental study; genetic risk factor; human model; imaging facilities; instrument; next generation; nonhuman primate; tool

Investigators at the Broad Institute are actively developing ever more precise molecular and genetic tools for psychiatric research, harnessing powerful human model systems to understand the neurobiological results of genetic risk factors; and developing new computational and experimental approaches for unbiased mapping of mammalian brains. Large scale volumetric imaging of brain tissue would help achieve all these goals by enabling rapid evaluation of the performance of new tool compounds, and unbiased investigation of brain-wide cell type distributions and projection patterns. The ideal imaging technology for these experiments is selective plane illumination microscopy, or light-sheet microscopy, which, when performed in cleared brain tissue can avoid photobleaching of thick samples while achieving high volumetric scan rates. Large field-of-view light sheet microscopes have been developed, but, despite the potential advantage of this technology, Broad Institute investigators do not have access to such an instrument either at the Broad or at surrounding imaging facilities. To address this need, an ultra large field-of-view light sheet microscope, the mesoSPIM, will be built in the Broad Institute’s new Optical Profiling Platform according to clearly established specifications published by its inventors (Voigt, et al. 2019). The instrument will be accompanied by tissue clearing accessories permitting mental health researchers to clear, label, and image brain tissue in a highly automated and robust fashion. The OPP’s role at the Broad Institute is specifically to support such custom-built, cutting-edge technology for the broader research community. This is accomplished by a team of automation engineers, professional optics staff, computational biologists, and academic trainees who work together to both develop the next generation of tools and support existing technologies. This experienced team will build and manage the mesoSPIM for the benefit of the Broad mental health research community at minimal cost to users. Implemented in this way, the mesoSPIM will rapidly provide results characterizing the location and anatomical structure of newly identified cell types in the mouse and non-human primate brains; and will provide large-scale cell type catalogs and distributions across the mammalian brain.

布罗德研究所的研究人员正在积极开发更精确的分子和遗传工具 精神病学研究，利用强大的人体模型系统来了解神经生物学结果 遗传风险因素；并开发新的计算和实验方法来进行无偏映射 哺乳动物大脑的大规模体积成像将有助于实现所有这些目标。 快速评估新工具化合物的性能，并对全脑细胞类型进行公正的研究 这些实验的理想成像技术是选择性平面。 照明显微镜或光片显微镜，在透明脑组织中进行时可以避免 对厚样品进行光漂白，同时实现高体积扫描速率。 显微镜已经开发出来，但是，尽管这项技术具有潜在优势，布罗德研究所 调查人员在布罗德研究所或周围的成像设施中都无法使用此类仪器。 为了满足这一需求，将在 Broad 研究所构建超大视场光片显微镜 mesoSPIM 研究所的新光学分析平台根据其发明者发布的明确制定的规范 （Voigt 等人，2019 年）。该仪器将配有有助于心理健康的组织清理配件。 研究人员以高度自动化和稳健的方式对脑组织进行清理、标记和成像。 布罗德研究所专门为更广泛的研究支持这种定制的尖端技术 这是由自动化工程师、专业光学人员、计算人员组成的团队完成的。 生物学家和学术实习生共同开发下一代工具和支持 这个经验丰富的团队将为了 Broad 的利益而构建和管理 mesoSPIM。 通过这种方式，心理健康研究界将以最低的成本实施 mesoSPIM。 提供表征小鼠中新鉴定的细胞类型的位置和解剖结构的结果 和非人类灵长类动物的大脑；并将提供大规模的细胞类型目录和分布 哺乳动物的大脑。