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3D virtual Histopathology of Cardiac Tissue from Covid-19 Patients based on Phase-Contrast X-ray Tomography

Marius Reichardt, Patrick Møller Jensen, Vedrana Andersen Dahl, Anders Bjorholm Dahl, View ORCID ProfileMaximilian Ackermann, Harshit Shah, Florian Länger, Christopher Werlein, Mark Kühnel, Danny Jonigk, View ORCID ProfileTim Salditt
doi: https://doi.org/10.1101/2021.09.16.460594
Marius Reichardt
1Institut für Röntgenphysik, Georg-August-Universität Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen, Germany
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Patrick Møller Jensen
2Technical University of Denmark, Richard Petersens Plads, 2800 Kgs. Lyngby, Denmark
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Vedrana Andersen Dahl
2Technical University of Denmark, Richard Petersens Plads, 2800 Kgs. Lyngby, Denmark
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Anders Bjorholm Dahl
2Technical University of Denmark, Richard Petersens Plads, 2800 Kgs. Lyngby, Denmark
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Maximilian Ackermann
3Institute of Anatomy and Cell Biology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany
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  • ORCID record for Maximilian Ackermann
Harshit Shah
4Medizinische Hochschule Hannover (MHH),Carl-Neuberg-Str. 1, 30625 Hannover, Germany
5Deutsches Zentrum für Lungenforschung (DZL), Hannover (BREATH)
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Florian Länger
4Medizinische Hochschule Hannover (MHH),Carl-Neuberg-Str. 1, 30625 Hannover, Germany
5Deutsches Zentrum für Lungenforschung (DZL), Hannover (BREATH)
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Christopher Werlein
4Medizinische Hochschule Hannover (MHH),Carl-Neuberg-Str. 1, 30625 Hannover, Germany
5Deutsches Zentrum für Lungenforschung (DZL), Hannover (BREATH)
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Mark Kühnel
4Medizinische Hochschule Hannover (MHH),Carl-Neuberg-Str. 1, 30625 Hannover, Germany
5Deutsches Zentrum für Lungenforschung (DZL), Hannover (BREATH)
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Danny Jonigk
4Medizinische Hochschule Hannover (MHH),Carl-Neuberg-Str. 1, 30625 Hannover, Germany
5Deutsches Zentrum für Lungenforschung (DZL), Hannover (BREATH)
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  • For correspondence: jonigk.danny@mh-hannover.de tsaldit@gwdg.de
Tim Salditt
1Institut für Röntgenphysik, Georg-August-Universität Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen, Germany
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  • ORCID record for Tim Salditt
  • For correspondence: jonigk.danny@mh-hannover.de tsaldit@gwdg.de
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Abstract

For the first time, we have used phase-contrast x-ray tomography to characterize the three-dimensional (3d) structure of cardiac tissue from patients who succumbed to Covid-19. By extending conventional histopatholocigal examination by a third dimension, the delicate pathological changes of the vascular system of severe Covid-19 progressions can be analyzed, fully quantified and compared to other types of viral myocarditis and controls. To this end, cardiac samples with a cross section of 3.5mm were scanned at the synchrotron in a parallel beam configuration. The vascular network was segmented by a deep learning architecture suitable for 3d datasets (V-net), trained by sparse manual annotations. Pathological alterations of vessels, concerning the variation of diameters and the amount of small holes, were observed, indicative of elevated occurrence of intussusceptive angiogenesis, also confirmed by scanning electron microscopy. Further, we implemented a fully automated analysis of the tissue structure in form of shape measures based on the structure tensor. The corresponding distributions show that the histopathology of Covid-19 differs from both influenza and typical coxsackie virus myocarditis.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* Shared senior authorship

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 18, 2021.
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3D virtual Histopathology of Cardiac Tissue from Covid-19 Patients based on Phase-Contrast X-ray Tomography
Marius Reichardt, Patrick Møller Jensen, Vedrana Andersen Dahl, Anders Bjorholm Dahl, Maximilian Ackermann, Harshit Shah, Florian Länger, Christopher Werlein, Mark Kühnel, Danny Jonigk, Tim Salditt
bioRxiv 2021.09.16.460594; doi: https://doi.org/10.1101/2021.09.16.460594
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3D virtual Histopathology of Cardiac Tissue from Covid-19 Patients based on Phase-Contrast X-ray Tomography
Marius Reichardt, Patrick Møller Jensen, Vedrana Andersen Dahl, Anders Bjorholm Dahl, Maximilian Ackermann, Harshit Shah, Florian Länger, Christopher Werlein, Mark Kühnel, Danny Jonigk, Tim Salditt
bioRxiv 2021.09.16.460594; doi: https://doi.org/10.1101/2021.09.16.460594

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