Effect of CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor on pulmonary ventilation derived by 3D phase-resolved functional lung MRI in cystic fibrosis patients

Abstract

Objectives To investigate whether 3D phase-resolved functional lung (PREFUL)-MRI parameters are suitable to measure response to elexacaftor/tezacaftor/ivacaftor (ETI) therapy and their association with clinical outcomes in cystic fibrosis (CF) patients. Methods Twenty-three patients with CF (mean age: 21; age range: 14–46) underwent MRI examination at baseline and 8–16 weeks after initiation of ETI. Morphological and 3D PREFUL scans assessed pulmonary ventilation. Morphological images were evaluated using a semi-quantitative scoring system, and 3D PREFUL scans were evaluated by ventilation defect percentage (VDP) values derived from regional ventilation (RVent) and cross-correlation maps. Improved ventilation volume (IVV) normalized to body surface area (BSA) between baseline and post-treatment visit was computed. Forced expiratory volume in 1 second (FEV1) and mid-expiratory flow at 25% of forced vital capacity (MEF25), as well as lung clearance index (LCI), were assessed. Treatment effects were analyzed using paired Wilcoxon signed-rank tests. Treatment changes and post-treatment agreement between 3D PREFUL and clinical parameters were evaluated by Spearman’s correlation. Results After ETI therapy, all 3D PREFUL ventilation markers (all p < 0.0056) improved significantly, except for the mean RVent parameter. The BSA normalized IVVRVent was significantly correlated to relative treatment changes of MEF25 and mucus plugging score (all |r| > 0.48, all p < 0.0219). In post-treatment analyses, 3D PREFUL VDP values significantly correlated with spirometry, LCI, MRI global, morphology, and perfusion scores (all |r| > 0.44, all p < 0.0348). Conclusions 3D PREFUL MRI is a very promising tool to monitor CFTR modulator–induced regional dynamic ventilation changes in CF patients. Clinical relevance statement 3D PREFUL MRI is sensitive to monitor CFTR modulator–induced regional ventilation changes in CF patients. Improved ventilation volume correlates with the relative change of mucus plugging, suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement. Key Points • 3D PREFUL MRI–derived ventilation maps show significantly reduced ventilation defects in CF patients after ETI therapy. • Significant post-treatment correlations of 3D PREFUL ventilation measures especially with LCI, FEV1 %pred, and global MRI score suggest that 3D PREFUL MRI is sensitive to measure improved regional ventilation of the lung parenchyma due to reduced inflammation induced by ETI therapy in CF patients. • 3D PREFUL MRI–derived improved ventilation volume (IVV) correlated with MRI mucus plugging score changes suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement 8–16 weeks after ETI therapy.

Contrast agent-free functional magnetic resonance imaging with matrix pencil decomposition to quantify abnormalities in lung perfusion and ventilation in patients with cystic fibrosis

“…Similarly, PREFUL-MRI was used successfully for assessment of lung ventilation in patients with chronic pulmonary diseases including CF. ( 14 , 51 , 52 , 58 ) The ultra-fast balanced steady-state free precession sequence of the MP-MRI technique has the advantage that lung perfusion and ventilation can be assessed simultaneously, leading to an examination time of 6–7 min for complete acquisition of MP-MRI data in free breathing, whereas slightly longer examination time has been reported in studies using PREFUL-MRI ( 14 ). On the other hand, there are obvious advantages of PREFUL-MRI over MP-MRI.…”

“…Over the past 15 years, magnetic resonance imaging (MRI) has emerged as an alternative to detect lung abnormalities in CF. (8)(9)(10)(11) Advantages of MRI compared to CT are the absence of potentially harmful ionizing radiation, as well as the ability to perform simultaneous functional imaging studies for a combined assessment of lung morphology and functional parameters such as lung perfusion (12)(13)(14)(15)(16).…”