Longitudinal Monitoring of Lumacaftor/Ivacaftor Response in Young Children with Cystic Fibrosis Lung Disease Using ¹²⁹Xe MRI

Hyperpolarized ¹²⁹Xe magnetic resonance imaging (MRI) can sensitively detect subtle abnormalities in subjects with pulmonary disease. In this work, we assess lung disease progression and treatment response to Lumacaftor/Ivacaftor in patients with cystic fibrosis.

18 cystic fibrosis (CF) patients underwent a longitudinal study: nine subjects (8.7±2.4years, 3M/6F) initiated lumacaftor/ivacaftor therapy (48±51days post-Visit 1), and 9 (15.3±4.3years, 5M/4F) served as controls. Spirometry, multiple breath washout (Lung Clearance Index, LCI_2.5), and ¹²⁹Xe MRI were acquired at baseline, short-term (6±3months), and long-term (15±4months) follow-ups. Changes in spirometry measurements, LCI, ventilation defect percentage (VDP), and defect distribution index (DDI) assessed by ¹²⁹Xe MRI, were compared between groups using non-parametric tests.

The control group was significantly older (P=0.0028) and trended toward higher initial VDP (14.7±8.1% vs 6.9±6.0%) and DDI (14.4±24.7 vs 4.7±4.3). Baseline spirometry and LCI showed no differences between groups. In the treatment group, VDP and DDI remained stable after treatment (ΔVDP₁₂= -0.56±2.1%, ΔDDI₁₂= 1.1±4.0) but the change was significantly lower than in controls (ΔVDP₁₂= 2.75±2.82%, P=0.018; DDI₁₂= 8.88±7.42, P=0.007). From Visit-2 to Visit-3, VDP increased significantly in the treatment group (ΔVDP₂₃ = 3.33±2.79%, P=0.025) versus controls (ΔVDP₂₃= -1.7±4.8%). No significant changes occurred in spirometry or LCI.

¹²⁹Xe MRI demonstrated high sensitivity in detecting functional changes between pediatric CF patients on and off modulator therapy. In the short term, ¹²⁹Xe ventilation measures remained stable with modulator therapy and demonstrated declines in the 2 years following. These findings highlight ¹²⁹Xe MRI's potential as a valuable clinical tool for monitoring lung function and disease progression, even with small cohorts of patients.