Functional Lung Imaging Identifies Peripheral Ventilation Changes in ꞵ-ENaC Mice.

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.