Dynamic Perfluorinated Gas MRI Shows Improved Lung Ventilation in People with Cystic Fibrosis after Elexacaftor/Tezacaftor/Ivacaftor: An Observational Study.

The availability of highly effective CFTR modulators is revolutionizing the treatment of cystic fibrosis (CF) and drastically improving outcomes. MRI-based imaging modalities are now emerging as highly sensitive endpoints, particularly in the setting of mild lung disease. Adult CF patients were recruited from a single center prior to starting treatment with E/T/I. The following studies were obtained before and after one month on treatment: spirometry, multiple breath nitrogen washout (MBW), 1 H UTE MRI (structural images) and 19 F MRI (ventilation images). Changes between visits were calculated, as were correlations between FEV 1 , lung clearance index (LCI), MRI structural scores, and MRI-based ventilation descriptors. Eight subjects had complete datasets for evaluation. Consistent with prior clinical trials, FEV 1 and LCI improved after 28 days of E/T/I use. 1 H UTE MRI detected improvements in bronchiectasis/airway wall thickening score and mucus plugging score after 28 days of therapy. 19 F MRI demonstrated improvements in fractional lung volume with slow gas washout time (FLV↑tau2) and ventilation defect percentage (VDP). Improvements in FLV↑tau2 and VDP correlated with improvement in FEV 1 (r = 0.81 and 0.86, respectively, p < 0.05). This observational study establishes the ability of 19 F MRI and 1 H UTE MRI to detect improvements in lung structure and function after E/T/I treatment. This study supports further development of 19 F MRI and 1 H UTE MRI as outcome measures for cystic fibrosis research and drug development.