Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography
Claire Walsh, Paul Tafforeau, Willi L. Wagner, Daniyal J. Jafree, Alexandre Bellier, Christopher Werlein, Mark Kühnel, Elodie Boller, Simon Walker‐Samuel, Jan Lukas Robertus, David A. Long, Joseph Jacob, Sebastian Marussi, Emmeline Brown, Natalie Holroyd, Danny Jonigk, Maximilian Ackermann, Peter Lee
Abstract
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).