Hyperpolarized Xenon 129 MRI to Evaluate Regional Gas-Exchange Abnormalities in Cystic Fibrosis Lung Disease.

Purpose To assess pulmonary gas exchange in participants with cystic fibrosis (CF) relative to control participants, evaluate the effect of CF transmembrane conductance regulator (CFTR) modulator therapy, and assess subclinical lung disease using xenon 129 (129Xe) MRI. Materials and Methods Participants with CF and control participants were prospectively enrolled between October 2019 and February 2024 and underwent 129Xe MRI and spirometry. Images from gaseous xenon, xenon dissolved in pulmonary capillary red blood cells (RBCs), and dissolved in the gas-exchange membrane (interstitial tissue and capillary plasma) were binned into three compartments to generate maps of ventilation, RBC transfer, and membrane uptake. Spirometric and imaging differences between participants with CF and control participants were assessed using analysis of variance with Tukey post hoc corrections, and associations were analyzed using Kendall rank correlation. Results Sixty-one participants with CF (median age, 14.2 years; IQR, 10.0-19.7 years; 33 female) and 47 controls (median age, 24.9 years; IQR, 20.9-29.2 years; 25 males) were included. For participants with CF, spirometry (percent predicted) was normal: forced expiratory volume after 1 second (median, 98.2%; IQR, 87.2%-109%), forced vital capacity (median, 104%; IQR, 96.8%-112%), and forced expiratory flow between 25% and 75% forced vital capacity (median, 88.1%; IQR, 69.9%-108%). Participants with CF had a higher ventilation defect percentage (2.50% vs 1.40%; P < .001), RBC transfer (0.00354 vs 0.00325; P = .0104), and membrane uptake (0.0096 vs 0.0076; P < .001) than controls. Membrane uptake correlated with elevated RBC transfer (τ = 0.62; P < .001) for participants with CF on and off CFTR modulator therapy. Conclusion Participants with CF had higher RBC transfer and membrane uptake than control participants. Membrane uptake was elevated in participants with CF exhibiting normal spirometry and receiving highly effective CFTR modulator therapy. Keywords: Adults and Pediatrics, Lung, MR-Hyperpolarization, MR-Functional Lung Imaging Supplemental material is available for this article. © RSNA, 2026.