New insights into lung tissue in COVID-19 disease

Date:
August 21, 2020
Source:
University of Go"ttingen
Summary:
Researchers have developed a new three-dimensional imaging technique
to visualize tissue damage in severe COVID-19.



FULL STORY ========================================================================== Physicists at the University of Go"ttingen, together with pathologists and
lung specialists at the Medical University of Hannover, have developed
a three- dimensional imaging technique that enables high resolution
and three- dimensional representation of damaged lung tissue following
severe Covid-19.

Using a special X-ray microscopy technique, they were able to image
changes caused by the coronavirus in the structure of alveoli (the tiny
air sacs in the lung) and the vasculature. The results of the study were published in the research journal eLife.


==========================================================================
In severe Covid-19 disease, the researchers observed significant changes
in the vasculature, inflammation, blood clots and "hyaline membranes,"
which are composed of proteins and dead cells deposited on the alveolar
walls, which make gas exchange difficult or impossible. With their new
imaging approach, these changes can be visualized for the first time in
larger tissue volumes, without cutting and staining or damaging the tissue
as in conventional histology. It is particularly well suited for tracing
small blood vessels and their branches in three dimensions, localizing
cells of the immune systems which are recruited to the inflammation
sites, and measuring the thickness of the alveolar walls. Due to the three-dimensional reconstruction, the data could also be used to simulate
gas exchange.

"Using zoom tomography, large areas of lung tissue embedded in wax can be scanned enabling detailed examination to locate particularly interesting
areas around inflammation, blood vessels or bronchial tubes," says lead
author Professor Tim Salditt from the Institute of X-ray Physics at the University of Go"ttingen. Since X-rays penetrate deep into tissue, this
enables scientists to understand the relation between the microscopic
tissue structure and the larger functional architecture of an organ. This
is important, for example, to visualize the tree of blood vessels down
to the smallest capillaries.

The authors foresee that this new X-ray technique will be an extension to traditional histology and histopathology, areas of study which go back
to the 19th century when optical microscopes had just become available
and pathologists could thereby unravel the microscopic origins of many diseases.

Even today, pathologists still follow the same basic steps to prepare
and investigate tissue: chemical fixation, slicing, staining and
microscopy. This traditional approach, however, is not sufficient if three-dimensional images are required or if large volumes have to be
screened, digitalized or analysed with computer programmes.

Three-dimensional imaging is well known from medical computerized
tomography (CT). However, the resolution and contrast of this conventional technique are not sufficient to detect the tissue structure with cellular
or sub-cellular resolution. Therefore, the authors used "phase contrast,"
which exploits the different propagation velocities of X-rays in tissue to generate an intensity pattern on the detector. Salditt and his research
group at the Institute for X- ray Physics developed special illumination
optics and algorithms to reconstruct sharp images from these patterns, an approach which they have now adapted for the study of lung tissue affected
by severe progression of Covid-19. The Go"ttingen team could record lung
tissue at scalable size and resolution, yielding both larger overviews
and close-up reconstructions. Depending on the setting, their method can
even yield structural details below the resolution of conventional light microscopy. To achieve this, the researchers used highly powerful X-ray radiation generated at the PETRAIII storage ring of the German Electron Synchrotron (DESY) in Hamburg.

As was the case when the modern microscope was invented 150 years ago, significant progress has resulted from collaboration between physicists
and medical researchers. The interdisciplinary research team hopes
that the new method will support the development of treatment methods, medicines to prevent or alleviate severe lung damage in Covid-19, or
to promote regeneration and recovery. "It is only when we can clearly
see and understand what is really going on, that we can develop targeted interventions and drugs," adds Danny Jonigk (Medical University Hannover),
who led the medical part of the interdisciplinary study.


========================================================================== Story Source: Materials provided by University_of_Go"ttingen. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Marina Eckermann, Jasper Frohn, Marius Reichardt, Markus Osterhoff,
Michael Sprung, Fabian Westermeier, Alexandar Tzankov, Mark
Ku"hnel, Danny Jonigk, Tim Salditt. 3d virtual pathohistology of
lung tissue from COVID-19 patients based on phase contrast x-ray
tomography. eLife, 2020; 9 DOI: 10.7554/eLife.60408 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200821103909.htm

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