3D virtual histopathology of cardiac tissue from Covid-19 patients based on phase-contrast X-ray tomography
- Georg-August-Universität Göttingen, Germany
- Technical University of Denmark, Denmark
- University Medical Center of the Johannes Gutenberg University Mainz, Germany
- Medical University Hannover, Germany
Abstract
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 histopathological 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 a laboratory setup as well as at a parallel beam setup at a synchrotron radiation facility. 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 high resolution cone beam X-ray tomography and scanning electron microscopy. Furthermore, 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.
Data availability
The tomographic datasets recorded in WG configuration as well as the PB datasets used for the segmentation of the vascular system and the respective laboratory datasets were uploaded to https://doi.org/10.5281/zenodo.4905971.Additional data (raw data, PB and laboratory reconstructions, structure tensor analysis) is curated here at University ofGöttingen and at DESY can be obtained upon request from the corresponding author (tsaldit@gwdg.de); due to the extremely large size >15TB it cannot presently be uploaded easily to a public repository.The implementation of the structure tensor analysis is provided in https://lab.compute.dtu.dk/patmjen/structure-tensor.The neural network code used for the segmentation of the vasculature was uploaded to GitHub (github.com/patmjen/blood-vessel-segmentation)
Article and author information
Author details
Maximilian Ackermann
Funding
Bundesministerium für Bildung und Forschung (Max Planck School Matter to Life)
- Marius Reichardt
- Tim Salditt
Bundesministerium für Bildung und Forschung (05K19MG2)
- Tim Salditt
Deutsche Forschungsgemeinschaft (EXC 2067/1-390729940)
- Tim Salditt
H2020 European Research Council (XHale,771883)
- Danny Jonigk
Deutsche Forschungsgemeinschaft (KFO311 (project Z2))
- Danny Jonigk
Hanseatic League of Science
- Patrick Moller Jensen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Hina Chaudhry, Harvard University, United States
Ethics
Human subjects: Formalin-fixed paraffin-embedded tissue blocks of control hearts, influenza and coxsackie virus myocarditis hearts were retrieved from archived material from the Institute of Pathology at Hannover Medical School in accordance with the local ethics committee (ethics vote number: 1741-2013 and 2893-2015). Formalin-fixed paraffin-embedded tissue blocks of COVID-19 autopsy cases were retrieved after written consent in accordance with the local ethics committee at Hannover medical school (ethics vote number: 9022 BO K 2020)
Version history
- Received: June 17, 2021
- Preprint posted: September 18, 2021 (view preprint)
- Accepted: December 10, 2021
- Accepted Manuscript published: December 21, 2021 (version 1)
- Version of Record published: January 10, 2022 (version 2)
Copyright
© 2021, Reichardt et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 4,991
- Page views
-
- 595
- Downloads
-
- 16
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
3D virtual histopathology of cardiac tissue from Covid-19 patients based on phase-contrast X-ray tomography
eLife 10:e71359.
https://doi.org/10.7554/eLife.71359
Further reading
-
- Epidemiology and Global Health
Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0%-16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2.
-
- Epidemiology and Global Health
Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
