The assessment of short- and long-term changes in lung function in cystic fibrosis using 129Xe MRI

Introduction: Xenon-129 (Xe-129) ventilation magnetic resonance imaging (MRI) is sensitive to detect early cystic fibrosis (CF) lung disease and response to treatment. Xe-129-MRI could play a significant role in clinical trials and patient management. Here we present data on the repeatability of imaging measurements and their sensitivity to longitudinal change. Methods: 29 children and adults with CF and a range of disease severity were assessed twice, a median (interquartile range (IQR)) of 16.0 (14.4-19.5) months apart. Patients underwent Xe-129-MRI, lung clearance index (LCI), body plethysmography and spirometry at both visits. 11 patients repeated Xe-129-MRI in the same session to assess the within-visit repeatability. The ventilation defect percentage (VDP) was the primary metric calculated from Xe-129-MRI. Results: At baseline, mean +/- SD age was 23.0 +/- 11.1 years and forced expiratory volume in 1 s (FEV1) z-score was -2.2 +/- 2.0. Median (IQR) VDP was 9.5 (3.4-31.6)% and LCI was 9.0 (7.7-13.7). Within- and inter-visit repeatability of VDP was high. At 16 months there was no single trend of Xe-129-MRI disease progression. Visible Xe-129-MRI ventilation changes were common, which reflected changes in VDP. Based on the within-visit repeatability, a significant short-term change in VDP is >+/- 1.6%. For longer-term follow-up, changes in VDP of up to +/- 7.7% can be expected, or +/- 4.1% for patients with normal FEV1. No patient had a significant change in FEV1; however, 59% had change in VDP >+/- 1.6%. In patients with normal FEV1, there were significant changes in ventilation and in VDP. Conclusions: Xe-129-MRI is a highly effective method for assessing longitudinal lung disease in patients with CF. VDP has great potential as a sensitive clinical outcome measure of lung function and end-point for clinical trials.