Free-breathing Functional Pulmonary MRI: Response to Bronchodilator and Bronchoprovocation in Severe Asthma

Abstract

Ventilation heterogeneity is a hallmark feature of asthma. Our objective was to evaluate ventilation heterogeneity in patients with severe asthma, both pre- and post-salbutamol, as well as post-methacholine (MCh) challenge using the lung clearance index, free-breathing pulmonary 1H magnetic resonance imaging (FDMRI), and inhaled-gas MRI ventilation defect percent (VDP). Sixteen severe asthmatics (49 ± 10 years) provided written informed consent to an ethics board-approved protocol. Spirometry, plethysmography, and multiple breath nitrogen washout to measure the lung clearance index were performed during a single visit within 15 minutes of MRI. Inhaled-gas MRI and FDMRI were performed pre- and post-bronchodilator to generate VDP. For asthmatics with forced expiratory volume in 1 second (FEV1) >70%predicted, MRI was also performed before and after MCh challenge. Wilcoxon signed-rank tests, Spearman correlations, and a repeated-measures analysis of variance were performed. Hyperpolarized 3He (P = .02) and FDMRI (P = .02) VDP significantly improved post-salbutamol and for four asthmatics who could perform MCh (n = 4). 3He and FDMRI VDP significantly increased at the provocative concentration of MCh, resulting in a 20% decrease in FEV1 (PC20) and decreased post-bronchodilator (P = .02), with a significant difference between methods (P = .01). FDMRI VDP was moderately correlated with 3He VDP (ρ = .61, P = .01), but underestimated VDP relative to 3He VDP (-6 ± 9%). Whereas 3He MRI VDP was significantly correlated with the lung clearance index, FDMRI was not (ρ = .49, P = .06). FDMRI VDP generated in free-breathing asthmatic patients was correlated with static inspiratory breath-hold 3He MRI VDP but underestimated VDP relative to 3He MRI VDP. Although less sensitive to salbutamol and MCh, FDMRI VDP may be considered for asthma patient evaluations at centers without inhaled-gas MRI.