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 129Xe 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, N2 MBW) at ≥ 2 of 4 visits (1, 6, 12, and 24 months post-ETI). Fractional ventilation (FV) and FV coefficient of variation (CoVFV) 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 ppFEV1, LCI and VDP was not significant with p = 0.68, 0.13 and 0.12, respectively), CoVFV demonstrated a small but significant increase (slope magnitude +0.001/month). Furthermore, two participants had elevated CoVFV despite normal VDP. Finally, MBW Xe-MRI metrics showed higher within-subject variability than PFTs/VDP (ICC: FV = 0.41, CoVFV = 0.55 vs. VDP/PFTs ≥ 0.92).

DATA

CONCLUSION

CoVFV 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.