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.
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)
Reviewing Editor
- Hina Chaudhry, Harvard University, United States
Publication 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.
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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
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- Epidemiology and Global Health
Background:
Affectionate touch, which is vital for mental and physical health, was restricted during the Covid-19 pandemic. This study investigated the association between momentary affectionate touch and subjective well-being, as well as salivary oxytocin and cortisol in everyday life during the pandemic.
Methods:
In the first step, we measured anxiety and depression symptoms, loneliness and attitudes toward social touch in a large cross-sectional online survey (N = 1050). From this sample, N = 247 participants completed ecological momentary assessments over 2 days with six daily assessments by answering smartphone-based questions on affectionate touch and momentary mental state, and providing concomitant saliva samples for cortisol and oxytocin assessment.
Results:
Multilevel models showed that on a within-person level, affectionate touch was associated with decreased self-reported anxiety, general burden, stress, and increased oxytocin levels. On a between-person level, affectionate touch was associated with decreased cortisol levels and higher happiness. Moreover, individuals with a positive attitude toward social touch experiencing loneliness reported more mental health problems.
Conclusions:
Our results suggest that affectionate touch is linked to higher endogenous oxytocin in times of pandemic and lockdown and might buffer stress on a subjective and hormonal level. These findings might have implications for preventing mental burden during social contact restrictions.
Funding:
The study was funded by the German Research Foundation, the German Psychological Society, and German Academic Exchange Service.
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- Epidemiology and Global Health
Background: Home-based self-sampling for human papillomavirus (HPV) testing may be an alternative for women not attending clinic-based cervical cancer screening.
Methods: We assessed barriers to care and motivators to use at-home HPV self-sampling kits during the COVID-19 pandemic as part of a randomized controlled trial evaluating kit effectiveness. Participants were women aged 30-65 and under-screened for cervical cancer in a safety-net healthcare system. We conducted telephone surveys in English/Spanish among a subgroup of trial participants, assessed differences between groups, and determined statistical significance at p<0.05.
Results: Over half of 233 survey participants reported that clinic-based screening (Pap) is uncomfortable (67.8%), embarrassing (52.4%), and discomfort seeing male providers (63.1%). The last two factors were significantly more prevalent among Spanish versus English speakers (66.4% vs. 30% (p=0.000) and 69.9 vs. 52.2% (p=0.006), respectively). Most women who completed the kit found Pap more embarrassing (69.3%), stressful (55.6%), and less convenient (55.6%) than the kit. The first factor was more prevalent among Spanish versus English speakers (79.6% vs. 53.38%, p=0.001) and among patients with elementary education or below.
Conclusions: The COVID-19 pandemic influenced most (59.5%) to participate in the trial due to fear of COVID, difficulty making appointments, and ease of using kits. HPV self-sampling kits may reduce barriers among under-screened women in a safety-net system.
Funding: This study is supported by a grant from the National Institute for Minority Health and Health Disparities (NIMHD, R01MD013715, PI: JR Montealegre).
Clinical trial number: NCT03898167.
