Comparison of Single‐Breath and Multi‐Breath Xe‐ MRI in the Longitudinal Assessment of Treatment in Children With Cystic Fibrosis

Background Elexacaftor/tezacaftor/ivacaftor (ETI) is a current standard therapy for pediatric cystic fibrosis (CF). Multiple‐breath washout 129 Xe MRI (MBW Xe‐MRI) is improved following 1 month of treatment. However, the utility of MBW Xe‐MRI over extended ETI treatment and its comparison to single‐breath Xe‐MRI and pulmonary function tests (PFTs) in monitoring disease progression remains unclear. Purpose To compare MBW Xe‐MRI and single‐breath Xe‐MRI in a small pediatric CF cohort at 1, 6, 12, and 24 months post‐ETI initiation. Study Type Prospective longitudinal cohort study. Subjects 14 participants (7 female, median age 15.5 [14, 17] years) with CF undergoing ETI. Field Strength/Sequence Xe‐MRI using a gradient echo sequence at 3T. Assessment A total of 12 participants completed MBW Xe‐MRI, single‐breath Xe‐MRI, and PFTs (spirometry, N 2 MBW) at ≥ 2 of 4 visits (1, 6, 12, and 24 months post‐ETI). Fractional ventilation (FV) and FV coefficient of variation (CoV FV ) maps were calculated from MBW Xe‐MRI. Ventilation defect percent (VDP) was calculated from single‐breath Xe‐MRI. Statistical Tests Longitudinal changes were analyzed using a linear mixed‐effects model (fixed effect: time, random intercept: participant). Significance via ANOVA F‐test, p < 0.05. Intra‐class correlation coefficients (ICC) were used to quantify between‐ and within‐subject variability. Results Data completeness (total number of acquired data points divided by expected data points across 14 participants, 4 visits) was ≥ 75%. While PFTs/VDP remained stable over 24 months (ICC ≥ 0.93; linear mixed‐effects model of time effect for ppFEV 1 , LCI and VDP was not significant with p = 0.68, 0.13 and 0.12, respectively), CoV FV demonstrated a small but significant increase (slope magnitude +0.001/month). Furthermore, two participants had elevated CoV FV despite normal VDP. Finally, MBW Xe‐MRI metrics showed higher within‐subject variability than PFTs/VDP (ICC: FV = 0.41, CoV FV = 0.55 vs. VDP/PFTs ≥ 0.92). Data Conclusion CoV FV may continue to evolve over 2 years in pediatric CF patients receiving ETI, particularly in individuals with persistent ventilation defects. Evidence Level 1. Stage of Technical Efficacy 2.