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

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，利用强大的人类模型系统来了解神经生物学结果， 遗传风险因素;开发新的计算和实验方法， 哺乳动物的大脑脑组织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，以及对全脑细胞类型的无偏见研究 分布和投影模式。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，当在透明的脑组织中进行时，可以避免 厚样品的光漂白，同时实现高体积扫描速率。大视场光片 显微镜已经开发出来，但是，尽管这项技术的潜在优势，布罗德研究所 调查人员在布罗德或周围的成像设施都无法使用这种仪器。 为了满足这一需求，将在布罗德建造一个超大视场光片显微镜，即mesoSPIM。 根据其发明者发布的明确规定的规格，研究所的新光学轮廓测量平台 （Voigt等人，2019）。该仪器将伴随着允许心理健康的组织清除配件 研究人员以高度自动化和强大的方式清除，标记和成像脑组织。在这方面， 布罗德研究所专门支持这种定制的尖端技术，用于更广泛的研究 社区这是由一个自动化工程师团队，专业的光学人员，计算 生物学家和学术实习生，他们共同开发下一代工具， 现有技术。这个经验丰富的团队将为Broad的利益构建和管理mesoSPIM 心理健康研究社区以最小的成本给用户。以这种方式实施，mesoSPIM将迅速 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在整个 哺乳动物的大脑

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.