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

Nat Methods. 2021 Dec;18(12):1532-1541. doi: 10.1038/s41592-021-01317-x. Epub 2021 Nov 4.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / pathology*
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Imaging, Three-Dimensional / methods*
  • Kidney / anatomy & histology
  • Lung / pathology*
  • SARS-CoV-2*
  • Synchrotrons
  • Tomography, X-Ray Computed / methods*