Biology subjects

Tschanz, S. A.

Publications and source records attributed to Tschanz, S. A..

3 recordsLinked to original sources

bioRxiv2022

The Cilialyzer - a freely available open-source software for a standardised identification of impaired mucociliary activity facilitating the diagnostic testing for PCD

Background and ObjectivePrimary ciliary dyskinesia (PCD) is a rare genetic disorder causing a defective ciliary structure, which predominantly leads to an impaired mucociliary clearance and associated airway disease. As there is currently no single diagnostic gold standard test, PCD is diagnosed by a combination of several methods comprising genetic testing and the examination of the ciliary structure and function. Among the approved diagnostic methods, only high-speed video microscopy (HSVM) allows to directly observe the ciliary motion and therefore, to directly assess ciliary function. In the present work, we present our recently developed freely available open-source software - termed "Cilialyzer", which has been specifically designed to support and facilitate the analysis of the mucociliary activity in respiratory epithelial cells captured by high-speed video microscopy. MethodsIn its current state, the Cilialyzer software enables clinical PCD diagnosticians to load, preprocess and replay the image sequences with a feature-rich replaying module facilitating the commonly performed qualitative visual assessment of ciliary function. The image processing methods made accessible through an intuitive user interface allow clinical specialists to comfortably compute the ciliary beating frequency (CBF), the activity map and the "frequency correlation length" - an observable getting newly introduced. Furthermore, the Cilialyzer contains a simple-to-use particle tracking interface to determine the mucociliary transport speed. ResultsThe Cilialyzer is fully written in the Python programming language and freely available under the terms of the MIT license. The proper functioning of the computational analysis methods constituting the Cilialyzer software is demonstrated by using simulated and representative sample data from clinical practice. ConclusionsThe Cilialyzer serves as a useful clinical tool for standardised PCD diagnostics and provides new quantitative information awaiting to be clinically evaluated using cohorts of PCD. As the Cilialyzer is freely available under the terms of a permissive open-source license, it serves as a ground frame for further development of computational methods aiming at the quantification and automation of the analysis of mucociliary activity captured by HSVM.

biophysics↗

bioRxiv2019

Pulmonary acini exhibit complex changes during postnatal rat lung development

Pulmonary acini represent the functional gas-exchanging units of the lung. Due to technical limitations, individual acini cannot be identified on microscopic lung sections. To overcome these limitations, we imaged the right lower lobes of instillation-fixed rat lungs from postnatal days P4, P10, P21, and P60 at the TOMCAT beamline of the Swiss Light Source synchrotron facility at a voxel size of 1.48 m. Individual acini were segmented from the three-dimensional data by closing the airways at the transition from conducting to gas exchanging airways. For a subset of acini (N=268), we followed the acinar development by stereologically assessing their volume and their number of alveoli. We found that the mean volume of the acini increases 23 times during the observed time-frame. The coeffcients of variation dropped from 1.26 to 0.49 and the difference between the mean volumes of the fraction of the 20 % smallest to the 20 % largest acini decreased from a factor of 27.26 (day 4) to a factor of 4.07 (day 60), i.e. shows a smaller dispersion at later time points. The acinar volumes show a very large variation early in lung development and homogenize during maturation of the lung by reducing their size distribution by a factor of 7 until adulthood. The homogenization of the acinar sizes hints at an optimization of the gas-exchange region in the lungs of adult animals and that acini of different size are not evenly distributed in the lungs. This likely leads to more homogeneous ventilation at later stages in lung development.

physiology↗

bioRxiv2019

Spatial intra- and intercellular alignment of respiratory cilia and its relation to function

Ciliary alignment is considered necessary to establish respiratory tract mucociliary clearance, and disorientation is often associated with primary ciliary dyskinesia. Therefore, there is an urgent need for a detailed analysis of ciliary orientation (CO). We used volume electron microscopy to examine CO relative to the tracheal long axis (TLA) by measuring the inter- and intracellular basal body orientation (BBO) and axonemal orientation (AO), which are considered to coincide, both equivalently indicating the effective stroke direction. Our results, however, reveal that only the mean BBO is aligned with the TLA, whereas the AO determines the effective stroke direction as well as the mucociliary transport direction. Furthermore, we show that even if the mean CO is conserved across cell boundaries, a considerable gradient in CO exists within individual cells, which we suspect to be crucial for the emergence of coordinated ciliary activity. Our findings provide new quantitative insight into CO and correlate this new structural information with mucociliary function.

cell biology↗