Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Airspace Diameter Map – a Quantitative Measurement of All Pulmonary Airspaces to Characterize Structural Lung Diseases

Version 1 : Received: 6 July 2023 / Approved: 7 July 2023 / Online: 7 July 2023 (07:12:13 CEST)

A peer-reviewed article of this Preprint also exists.

Blaskovic, S.; Anagnostopoulou, P.; Borisova, E.; Schittny, D.; Donati, Y.; Haberthür, D.; Zhou-Suckow, Z.; Mall, M.A.; Schlepütz, C.M.; Stampanoni, M.; Barazzone-Argiroffo, C.; Schittny, J.C. Airspace Diameter Map—A Quantitative Measurement of All Pulmonary Airspaces to Characterize Structural Lung Diseases. Cells 2023, 12, 2375. Blaskovic, S.; Anagnostopoulou, P.; Borisova, E.; Schittny, D.; Donati, Y.; Haberthür, D.; Zhou-Suckow, Z.; Mall, M.A.; Schlepütz, C.M.; Stampanoni, M.; Barazzone-Argiroffo, C.; Schittny, J.C. Airspace Diameter Map—A Quantitative Measurement of All Pulmonary Airspaces to Characterize Structural Lung Diseases. Cells 2023, 12, 2375.

Abstract

(1) Background: Stereological estimations significantly contributed to our anatomical and physiological understanding of the lung by providing an average distribution of measured parameters over the entire lung parenchyma. However, most structural lung diseases show a very inhomogeneous pattern of alterations. (2) Methods: We developed a novel protocol for the analysis of all pulmonary airspaces. Our pipeline starts with high-resolution synchrotron radiation-based X-ray tomographic microscopy (SRXTM) and consists of (i) image segmentation with the combination of the free machine-learning tool Ilastik and ImageJ and (ii) calculation of the airspace diameter distribution of an entire lung using a diameter map function. To evaluate the new pipeline, lungs from adult mice with cystic fibrosis (CF)-like lung disease (ENaC-transgenic mice) or mice with elastase-induced emphysema were compared to healthy controls. (3) Results: We were able to show the distribution of airspace diameters throughout the entire lung, as well as separately for the conducting airways and the gas-exchange area. In the pathobiological context, we observed an irregular widening of parenchymal airspaces in mice with CF-like lung disease and elastase-induced emphysema. Comparable results were obtained when analyzing lungs imaged with μCT, suggesting that our pipeline is applicable to different kinds of imaging modalities. (4) Conclusions: We conclude that the airspace diameter map is well suited for a detailed analysis of unevenly distributed structural alterations in chronic muco-obstructive lung diseases such as cystic fibrosis and COPD.

Keywords

lung disease; cystic fibrosis; pulmonary emphysema; image analysis; artificial intelligence; X-ray tomographic microscopy; micro-computed X-ray tomography / micro-CT; stereology.

Subject

Biology and Life Sciences, Biology and Biotechnology

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