Functional lung imaging identifies peripheral ventilation changes in mice with muco-obstructive lung disease

Reyne, N.; Smith, R.; Cmielewski, P.; Eikelis, N.; Nilsen, K.; Louise, J.; Duerr, J.; Mall, M. A.; Lawrence, M.; Parsons, D.; Donnelley, M.

doi:10.1101/2024.06.27.600946

bioRxiv · 10.1101/2024.06.27.600946

Functional lung imaging identifies peripheral ventilation changes in mice with muco-obstructive lung disease

Reyne, N.·Smith, R.·Cmielewski, P.·Eikelis, N.·Nilsen, K.·Louise, J.·Duerr, J.·Mall, M. A.·Lawrence, M.·Parsons, D.·Donnelley, M.

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Abstract

{beta}-ENaC-Tg mice serve as a relevant model of muco-obstructive lung disease, 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 lung function and mechanics analysis of the adult {beta}-ENaC-Tg model. {beta}-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. XV imaging demonstrated elevated ventilation defect percentage, mean specific ventilation, and ventilation heterogeneity in {beta}-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, {beta}-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. This research highlights the utility of XV imaging in evaluating ventilation defects in the {beta}-ENaC-Tg model and provides a comprehensive lung function analysis.

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Reyne, N., Smith, R., Cmielewski, P., Eikelis, N., Nilsen, K., Louise, J., Duerr, J., Mall, M. A., Lawrence, M., Parsons, D., Donnelley, M.. 2024-07-01. Functional lung imaging identifies peripheral ventilation changes in mice with muco-obstructive lung disease. https://doi.org/10.1101/2024.06.27.600946

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