Groundwork for a Synchrotron MicroCT Imaging Resource for Biology (SMIRB)

摘要 在目前的补充，我们要求资金建立和测试一个定制的透镜和摄像头系统，使 前所未有的12 mm直径视场和0.7 µm各向同性体素分辨率组合。我们 目标是扩大母公司合同中提出的同步加速器microCT的实用性， 在宽达12 mm的细胞分辨率样本上进行体积3D成像，例如人类活组织检查和小鼠 组织，并创建一个基于网络的综合生物图谱，提供一个关键的比较手段， 多尺度和多模式集成。这一努力将大大扩大 同步加速器microCT广泛的样品尺寸和模型系统的样品，这将产生3D 图像数据对计算表型组学的发展至关重要。我们打算把这些3D 在基于网络的“生物地图集”上公开提供图像，作为创建 多模型多模态参考图谱，包括组织学、3D图像数据和组学数据。我们将 通过三个相互关联的具体目标来实现这些目标：1）确认理论解决方案， 使用真实的样本的我们的内部microCT系统中的透镜和照相机系统的成像速度，2） 比较使用同步加速器的透镜和照相机系统获得的图像质量和图像速度 源与我们的本地源，和3）创建一个集成的基于Web的基础设施，以托管2D 和3D数据，并开发多种查看、标记和交叉引用工具， 基于比较的人类疾病动物模型验证。泛细胞，全体积的性质 将为组织学，免疫组织化学， 免疫荧光和转录组学、蛋白质组学和代谢组学数据。

Abstract In the current supplement, we request funds to build and test a custom lens and camera system that enables an unprecedented combination of 12 mm diameter field-of-view at 0.7 µm isotropic voxel resolution. Our objective is to expand the utility of synchrotron microCT proposed in the parent award to enable full- volume 3D imaging at cell resolution samples as wide as 12 mm, such as human biopsies and mouse tissues, and to create a web-based integrative bio-atlas that provides a critical means of comparisons, multi-scale, and multi-modal integrations. This effort will significantly broaden the application of synchrotron microCT to a wide range of sample sizes and model system samples, which will yield 3D image data critical for the development of computational phenomics. We intend to make these 3D images publicly available on a web-based “bio-atlas” to function as a foundation for the creation of a multi-model multi-modal reference atlas, inclusive of histology, 3D image data, and -omics data. We will achieve these goals through three interrelated specific aims: 1) confirm the theoretical resolution and imaging speed of the lens and camera system in our in-house microCT system using real samples, 2) compare image quality and image speeds obtained with the lens and camera system using synchrotron sources with those on our local source, and 3) create a integrative web-based infrastructure to host 2D and 3D data and develop multiple tools for viewing, labeling, and cross-referencing to allow comparison-based validation of animal models of human disease. The pan-cellular, full volume nature of the 3D images will add invaluable spatial information to histology, immunohistochemistry, immunofluorescence, and transcriptomics, proteomics, and metabolomics data.