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

Abstract

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 (FEV1) ≥85% predicted). Field Strength/Sequence: 3-T, two-dimensional (2D) gradient-echo (GRE) sequence. Assessment: Xe MRI, FEV1, and nitrogen multiple-breath wash-out for lung-clearance index (LCI2.5) 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 FEV1 %-predicted was 96.8% (86%–106%), and median LCI2.5 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.