Imaging Intact Human Organs with Local Resolution of Cellular Structures Using Hierarchical Phase-contrast Tomography via Nature Methods

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).

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By C. L. Walsh, P. Tafforeau, W. L. Wagner, D. J. Jafree, A. Bellier, C. Werlein, M. P. Kühnel, E. Boller, S. Walker-Samuel, J. L. Robertus, D. A. Long, J. Jacob, S. Marussi, E. Brown, N. Holroyd, D. D. Jonigk, M. Ackermann & P. D. Lee – 12 Nov 2021