Department of Mechanical Engineering, University College London, London, UK.
Centre for Advanced Biomedical Imaging, University College London, London, UK.
Nat Methods. 2021 Dec;18(12):1532-1541. doi: 10.1038/s41592-021-01317-x. Epub 2021 Nov 4.
Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)'s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19).
从器官到细胞尺度对完整人体器官进行三维成像，是生物医学成像的目标。为了应对这一挑战，我们开发了分级相衬断层摄影术（HiP-CT），这是一种利用欧洲同步辐射装置（ESRF）的超强光源（EBS）进行的 X 射线相位传播技术。ESRF-EBS 的空间相干性，结合我们的光束线设备、样品制备和扫描开发，使我们能够在整个人体器官的任何位置进行非破坏性的、三维（3D）扫描，分辨率逐渐提高。我们将 HiP-CT 应用于五种完整人体器官的成像：脑、肺、心脏、肾脏和脾脏。HiP-CT 提供了每个完整器官的结构概述，随后是多个更高分辨率的感兴趣区域的体积，捕获了器官型功能单元以及完整人体器官内某些特定的单个特化细胞。我们通过对完整人体肾脏中肾小球的定量和形态测量，以及对 2019 冠状病毒病（COVID-19）死者供体肺部组织结构的区域性变化的识别，展示了 HiP-CT 的潜在应用。
