Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography

Hierarchical phase-contrast tomography (HiP-CT) enables multiscale imaging of any region within an intact human organ down to cellular resolution. HiP-CT of five organ types revealed 3D morphological features in healthy and diseased tissue. 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).

Automated summary

Hierarchical phase-contrast tomography (HiP-CT) allows for multiscale imaging of intact human organs, providing insights into organ structures and cellular details. It offers multi-resolution imaging of organotypic functional units and individual specialized cells within intact human organs.