Assessing 129Xe multi-breath washout MRI response to elexacaftor/tezacaftor/ivacaftor intervention in pediatric CF.

Background: Monitoring multiple-breath washout (MBW) of a xenon tracer using magnetic resonance imaging (MBW Xe-MRI) provides quantitative regional measures of gas washout (fractional ventilation, FV) and spatial ventilation heterogeneity (coefficient of variation, CoV_FV) in pediatric CF lung disease, but has yet to be evaluated in an interventional setting.

Methods: 12 pediatric CF participants (median age 15.3 ± 2 years) completed MBW Xe-MRI, pulmonary function tests (PFTs) (spirometry, N₂ MBW for lung clearance index (LCI)) and single-breath Xe-MRI ventilation defect percent (VDP) measurements at baseline and 1-month post-initiation of elexacaftor/tezacaftor/ivacaftor (ETI) therapy. FV maps were calculated from MBW Xe-MRI washout images, and CoV_FV maps were derived from FV maps. Significant changes between visits were determined using a paired Wilcoxon signed-rank test. For correlations between absolute changes, Pearson's correlation was used.

Results: All measures changed significantly 1-month post-ETI therapy compared to baseline. For MRI metrics, median [IQR] VDP was significantly (P < 0.001) lower at 1 month (8.0 [3.7 12.4]) compared to baseline (17.8 [8.3 22.5]), FV was significantly (P < 0.05) higher at 1 month (0.42 [0.41 0.46]) compared to baseline (0.38 [0.33 0.44]), and CoV_FV was significantly (P < 0.001) lower at 1 month (0.06 [0.05 0.07]) compared to baseline (0.09 [0.08 0.12]). Both absolute and relative differences in CoV_FV and LCI were found to correlate highly (R = 0.92, P < 0.0001 and R = 0.91, P < 0.0001, respectively).

Conclusions: Functional information derived from MBW Xe-MRI, particularly CoV_FV, can be used to assess regional lung function in pediatric CF patients in an interventional setting and may be complementary to VDP and pulmonary function tests.