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

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.