Lung Function in Patients with Cystic Fibrosis before and during CFTR -Modulator Therapy Using 3D Ultrashort Echo Time MRI.

Background The triple combination of the cystic fibrosis transmembrane regulator (CFTR) modulators elexacaftor, tezacaftor, and ivacaftor (hereafter, elexacaftor/tezacaftor/ivacaftor) has a positive effect on lung function in patients with cystic fibrosis (CF). Purpose To compare three-dimensional (3D) ultrashort echo time (UTE) MRI functional lung data to common functional lung parameters in assessing lung function in patients with CF undergoing elexacaftor/tezacaftor/ivacaftor therapy. Materials and Methods In this prospective feasibility study, 16 participants with CF consented to undergo pulmonary MRI with a breath-hold 3D UTE sequence at baseline (April 2018-June 2019) and follow-up (April-July 2021). Eight participants received elexacaftor/tezacaftor/ivacaftor after baseline, and eight participants with unchanged treatment served as the control group. Lung function was assessed with body plethysmography and lung clearance index (LCI). Image-based functional lung parameters, such as ventilation inhomogeneity and ventilation defect percentage (VDP), were calculated from signal intensity change between MRI scans at inspiration and expiration. Metrics at baseline and follow-up were compared within groups (permutation test), correlation was tested (Spearman rank correlation), and 95% CIs were calculated (bootstrapping technique). Results MRI ventilation inhomogeneity correlated with LCI at baseline ( r = 0.92, P < .001) and follow-up ( r = 0.81, P = .002). Mean MRI ventilation inhomogeneity (baseline, 0.74 ± 0.15 [SD]; follow-up, 0.64 ± 0.11; P = .02) and mean VDP (baseline, 14.1% ± 7.4; follow-up, 8.5% ± 3.3; P = .02) decreased from baseline to follow-up in the treatment group. Lung function was stable over time (mean LCI: 9.3 turnovers ± 4.1 at baseline vs 11.5 turnovers ± 7.4 at follow-up; P = .34) in the control group. In all participants, correlation of forced expiratory volume in 1 second with MRI ventilation inhomogeneity was good at baseline ( r = -0.61, P = .01) but poor during follow-up ( r = -0.06, P = .82). Conclusion Noncontrast 3D UTE lung MRI functional parameters of ventilation inhomogeneity and VDP can be used to assess lung function over time in patients with CF and can add regional information to established global parameters, such as LCI. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Iwasawa in this issue.