Functional Lung Imaging Identifies Peripheral Ventilation Changes in ꞵ-ENaC Mice
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(Published version)
Date
2025
Authors
Reyne, N.
Smith, R.
Cmielewski, P.
Eikelis, N.
Nilsen, K.
Louise, J.
Duerr, J.
Mall, M.A.
Lawrence, M.
Parsons, D.
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Journal article
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Respirology, 2025; 30(4):335-345
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Nicole Reyne, Ronan Smith, Patricia Cmielewski, Nina Eikelis, Kris Nilsen, Jennie Louise, Julia Duerr, Marcus A. Mall, Mark Lawrence, David Parsons, Martin Donnelley
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Abstract
BACKGROUND AND OBJECTIVE: β-ENaC-Tg mice serve as a relevant model of muco-obstructive lung disease and diffuse-type emphysema, with impaired mucociliary clearance, mucus obstruction, chronic airway inflammation, structural lung damage, and altered lung function. The aim of this study was to undertake a comprehensive analysis of lung function and mechanics of the adult β-ENaC-Tg model. METHODS: Adult β-ENaC-Tg and wild-type littermates underwent X-ray velocimetry (XV) scans using a Permetium XV scanner (4DMedical, Melbourne, Australia). For comparative lung mechanics, lung function assessments were conducted with a flexiVent system (SCIREQ, Montreal, Canada). RESULTS: XV imaging demonstrated elevated ventilation defect percentage, mean specific ventilation, and ventilation heterogeneity in β-ENaC-Tg mice. Spatial analysis of ventilation maps indicated increased ventilation variability in the peripheral lung regions, as well as an increased proportion of under-ventilated areas. The flexiVent analysis indicated that compared to wild types, β-ENaC-Tg mice have a significantly more compliant lungs with increased inspiratory capacity, reduced tissue elastance, and increased hysteresivity (heterogeneity), suggesting loss of parenchymal integrity. CONCLUSION: This research highlights the utility of XV imaging in evaluating ventilation defects in the β-ENaC-Tg model and provides a comprehensive lung function analysis.
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© 2025 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.