Same‐Day Repeatability and 28‐Day Reproducibility of Xenon MRI Ventilation in Children With Cystic Fibrosis in a Multi‐Site Trial

Background MRI with xenon‐129 gas (Xe MRI) can assess airflow obstruction and heterogeneity in lung diseases. Specifically, Xe MRI may represent a sensitive modality for future therapeutic trials of cystic fibrosis (CF) therapies. The reproducibility of Xe MRI has not yet been assessed in the context of a multi‐site study. Purpose To determine the same‐day repeatability and 28‐day reproducibility of Xe MRI in children with CF. Study Type Four‐center prospective, longitudinal. Population Thirty‐eight children (18 females, 47%), median interquartile range (IQR) age 12 (9–14) years old, with mild CF (forced expiratory volume in 1 second (FEV 1 ) ≥85% predicted). Field Strength/Sequence 3‐T, two‐dimensional (2D) gradient‐echo (GRE) sequence. Assessment Xe MRI, FEV 1 , and nitrogen multiple‐breath wash‐out for lung‐clearance index (LCI 2.5 ) were performed. To assess same‐day reproducibility, Xe MRI was performed twice within the first visit, and procedures were repeated at 28 days. Xe hypoventilation was quantified using ventilation‐defect percentage (VDP) and reader‐defect volume (RDV). For VDP, hypoventilated voxels from segmented images were identified using a threshold of <60% mean whole‐lung signal and expressed as a percentage of the lung volume. For RDV, hypoventilation was identified by two trained readers and expressed as a percentage. Statistical Tests Inter‐site comparisons were conducted using Kruskal–Wallis nonparametric tests with Dunn's multiple‐comparisons tests. Differences for individuals were assessed using Wilcoxon matched‐pairs tests. Bland–Altman tests were used to evaluate same‐day repeatability, 28‐day reproducibility, and inter‐reader agreement. A P ‐value ≤0.05 was considered significant. Results Median FEV 1 %‐predicted was 96.8% (86%–106%), and median LCI 2.5 was 6.6 (6.3–7.4). Xe MRI had high same‐day reproducibility (mean VDP difference 0.12%, 95% limits of agreement −3.2, 3.4; mean RDV difference 0.42% −2.5, 3.3). At 28 days, 26/31 participants (84%) fell within the same‐day 95% limits of agreement. Data Conclusion Xe MRI may offer excellent same‐day and short‐term reproducibility. Evidence Level 2 Technical Efficacy Stage 2