Airspace Diameter Map—A Quantitative Measurement of All Pulmonary Airspaces to Characterize Structural Lung Diseases
Sanja Blaskovic,
Pinelopi Anagnostopoulou,
Elena Borisova,
Dominik Schittny,
Yves Donati,
David Haberthür,
Zhe Zhou-Suckow,
Marcus A. Mall,
Christian M. Schlepütz,
Marco Stampanoni,
Constance Barazzone-Argiroffo,
Johannes C. Schittny
Affiliations
Sanja Blaskovic
Institute of Anatomy, University of Bern, 3012 Bern, Switzerland
Pinelopi Anagnostopoulou
Medical School, University of Cyprus, Nicosia 2029, Cyprus
Elena Borisova
Institute of Anatomy, University of Bern, 3012 Bern, Switzerland
Dominik Schittny
Institute of Anatomy, University of Bern, 3012 Bern, Switzerland
Yves Donati
Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, 4 rue Gabrielle-Perret-Gentil, 1211 Genève, Switzerland
David Haberthür
Institute of Anatomy, University of Bern, 3012 Bern, Switzerland
Zhe Zhou-Suckow
Department of Translational Pulmonology, University Hospital Heidelberg, Translational Lung Research Center (TLRC), A Member of German Center for Lung Research (DZL), 69120 Heidelberg, Germany
Marcus A. Mall
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, 10115 Berlin, Germany
Christian M. Schlepütz
Swiss Light Source, Paul Scherrer Institute, 5232 Villigen, Switzerland
Marco Stampanoni
Swiss Light Source, Paul Scherrer Institute, 5232 Villigen, Switzerland
Constance Barazzone-Argiroffo
Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, 4 rue Gabrielle-Perret-Gentil, 1211 Genève, Switzerland
Johannes C. Schittny
Institute of Anatomy, University of Bern, 3012 Bern, Switzerland
(1) Background: Stereological estimations significantly contributed to our understanding of lung anatomy and physiology. Taking stereology fully 3-dimensional facilitates the estimation of novel parameters. (2) Methods: We developed a protocol for the analysis of all airspaces of an entire lung. It includes (i) high-resolution synchrotron radiation-based X-ray tomographic microscopy, (ii) image segmentation using the free machine-learning tool Ilastik and ImageJ, and (iii) calculation of the airspace diameter distribution using a diameter map function. To evaluate the new pipeline, lungs from adult mice with cystic fibrosis (CF)-like lung disease (βENaC-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, sugges-ting 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 distri-buted structural alterations in chronic muco-obstructive lung diseases such as cystic fibrosis and COPD.
