A two-center analysis of hyperpolarized 129Xe lung MRI in stable pediatric cystic fibrosis: Potential as a biomarker for multi-site trials

Background: The ventilation defect percent (VDP), measured from hyperpolarized (HP) Xe-129 magnetic resonance imaging (MRI), is sensitive to functional changes in cystic fibrosis (CF) lung disease. The purpose of this study was to measure and compare VDP from HP Xe-129 MRI acquired at two institutions in stable pediatric CF subjects with preserved lung function. Methods: This retrospective analysis included 26 participants from two institutions (18 CF, 8 healthy, age range 10-17). Pulmonary function tests, N-2 multiple breath washout (to measure lung clearance index, LCI), and HP Xe-129 MRI were performed. VDP measurements were compared between two trained analysts using mean-anchored linear binning. Correlations were investigated for VDP compared to the forced expiratory volume in one second (FEV1) and LCI. Results: VDP measurements agreed for the two analysts with an intraclass correlation coefficient of 0.99. In the combined dataset, VDP measured by Analyst 1 was 5.96 +/- 1.82% and 15.96 +/- 6.76% for the healthy and CF groups, respectively (p = .0004). Analyst 2 showed similar differences between healthy and CF (p = .0003). VDP measured by either analyst was shown to correlate with FEV1 (R-2 = 0.33, p = .003; and R-2 = 0.26, p = .009 for Analysts 1 and 2, respectively) and LCI (R-2 = 0.76, p < .0001; and R-2 = 0.77, p < .0001 for Analysts 1 and 2, respectively). Conclusion: HP Xe-129 MRI provides a robust measurement of ventilation heterogeneity in stable pediatric CF subjects at two sites. Since measurements performed at two sites yielded similar VDP values with near-identical values between different analysts, implementation of the technique in multi-center trials in CF appears feasible. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.