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@ARTICLE{Reichmann:607553,
author = {Reichmann, Jakob and Sarrazin, Clement and Schmale,
Sebastian and Blaurock, Claudia and Balkema-Buschmann, Anne
and Schmitzer, Bernhard and Salditt, Tim},
title = {3{D} imaging of {SARS}-{C}o{V}-2 infected hamster lungs by
{X}-ray phase contrast tomography enables drug testing},
journal = {Scientific reports},
volume = {14},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {PUBDB-2024-01925},
pages = {12348},
year = {2024},
abstract = {X-ray Phase Contrast Tomography (XPCT) based on wavefield
propagation has been established as a high resolution
three-dimensional (3D) imaging modality, suitable to
reconstruct the intricate structure of soft tissues, and the
corresponding pathological alterations. However, for
biomedical research, more is needed than 3D visualisation
and rendering of the cytoarchitecture in a few selected
cases. First, the throughput needs to be increased to cover
a statistically relevant number of samples. Second, the
cytoarchitecture has to be quantified in terms of
morphometric parameters, independent of visual impression.
Third, dimensionality reduction and classification are
required for identification of effects and interpretation of
results. To address these challenges, we here design and
implement a novel integrated and high throughput XPCT
imaging and analysis workflow for 3D histology,
pathohistology and drug testing. Our approach uses
semi-automated data acquisition, reconstruction and
statistical quantification. We demonstrate its capability
for the example of lung pathohistology in Covid-19. Using a
small animal model, different Covid-19 drug candidates are
administered after infection and tested in view of
restoration of the physiological cytoarchitecture,
specifically the alveolar morphology. To this end, we then
use morphometric parameter determination followed by a
dimensionality reduction and classification based on optimal
transport. This approach allows efficient discrimination
between physiological and pathological lung structure,
thereby providing quantitative insights into the
pathological progression and partial recovery due to drug
treatment. Finally, we stress that the XPCT image chain
implemented here only used synchrotron radiation for
validation, while the data used for analysis was recorded
with laboratory CT radiation, more easily accessible for
pre-clinical research.},
cin = {DOOR ; HAS-User},
ddc = {600},
cid = {I:(DE-H253)HAS-User-20120731},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3) / DFG project 390729940 -
EXC 2067: Multiscale Bioimaging: Von molekularen Maschinen
zu Netzwerken erregbarer Zellen (390729940) / SFB 1456 A03 -
Dimensionalitätsreduktion und Regression im
Wasserstein-Raum für quantitative 3D-Histologie (A03)
(456837373)},
pid = {G:(DE-HGF)POF4-6G3 / G:(GEPRIS)390729940 /
G:(GEPRIS)456837373},
experiment = {EXP:(DE-H253)P-P10-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38811688},
UT = {WOS:001235693100105},
doi = {10.1038/s41598-024-61746-4},
url = {https://bib-pubdb1.desy.de/record/607553},
}