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

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

doi:10.1038/s41592-021-01317-x

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.

Authors

C L Walsh^{1

2}, P Tafforeau³, W L Wagner^{4

5}, D J Jafree^{6

7}, A Bellier⁸, C Werlein⁹, M P Kühnel^{9

10}, E Boller¹¹, S Walker-Samuel¹², J L Robertus^{13

14}, D A Long⁶, J Jacob^{15

16}, S Marussi¹⁷, E Brown¹², N Holroyd¹², D D Jonigk^{18

19}, M Ackermann^{20

21}, P D Lee²²

Affiliations

¹ Department of Mechanical Engineering, University College London, London, UK. [email protected].
² Centre for Advanced Biomedical Imaging, University College London, London, UK. [email protected].
³ European Synchrotron Radiation Facility, Grenoble, France. [email protected].
⁴ Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany.
⁵ German Lung Research Centre (DZL), Translational Lung Research Centre Heidelberg (TLRC), Heidelberg, Germany.
⁶ Developmental Biology and Cancer Programme, Great Ormond Street Institute of Child Health, University College London, London, UK.
⁷ UCL MB/PhD Programme, Faculty of Medical Sciences, University College London, London, UK.
⁸ French Alps Laboratory of Anatomy (LADAF), Grenoble Alpes University, Grenoble, France.
⁹ Institute of Pathology, Hannover Medical School, Hannover, Germany.
¹⁰ German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
¹¹ European Synchrotron Radiation Facility, Grenoble, France.
¹² Centre for Advanced Biomedical Imaging, University College London, London, UK.
¹³ Department of Histopathology, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
¹⁴ National Heart and Lung Institute, Imperial College London, London, UK.
¹⁵ Centre for Medical Image Computing, University College London, London, UK.
¹⁶ UCL Respiratory, University College London, London, UK.
¹⁷ Department of Mechanical Engineering, University College London, London, UK.
¹⁸ Institute of Pathology, Hannover Medical School, Hannover, Germany. [email protected].
¹⁹ German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany. [email protected].
²⁰ Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. [email protected].
²¹ Institute of Pathology and Department of Molecular Pathology, Helios University Clinic Wuppertal, University of Witten-Herdecke, Wuppertal, Germany. [email protected].
²² Department of Mechanical Engineering, University College London, London, UK. [email protected].

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*

Abstract

Publication types

MeSH terms

Grants and funding