Regional pulmonary response to a methacholine challenge using hyperpolarized 3He magnetic resonance imaging

Background and objective: Spirometry is insensitive to small airway abnormalities in asthma. Our objective was to evaluate regional lung structure and function using hyperpolarized He-3 magnetic resonance imaging (MRI) before, during and after a methacholine challenge (MCh). Methods: Twenty-five asthmatics (mean age = 34 +/- 11 years) and eight healthy volunteers (HV) (mean age = 33 +/- 11 years) underwent spirometry, plethysmography and hyperpolarized He-3 MRI prior to a MCh. MRI was repeated following the MCh and again 25 min after salbutamol administration. He-3 MRI gas distribution was quantified using semiautomated segmentation of the ventilation defect percent (VDP). Tissue microstructure was measured using the He-3 apparent diffusion coefficient (ADC). Analysis of variance with repeated measures was used to evaluate changes at each time point as well as to determine interactions between regions of interest (ROI) and subject group. Pearson's correlations were performed to evaluate associations between He-3 MRI measurements and established clinical measures. Results: In asthmatics, but not HV, whole-lung ADC was increased post-MCh (P < 0.01). In asthmatics only, ADC was increased post-MCh in posterior ROI (P < 0.01) and all ROI in the superior-inferior direction (P < 0.01). VDP was increased in posterior and inferior ROI (P < 0.001). There was a correlation between VDP and specific airway resistance (r = 0.74, P < 0.0001), dyspnoea score (r = 0.66, P < 0.01) and fractional exhaled nitric oxide (r = 0.45, P < 0.05). Conclusions: We evaluated the regional pulmonary response to methacholine and salbutamol using 3He MRI and showed heterogeneous VDP and ADC consistent with bronchoconstriction and gas trapping, respectively, post-MCh. These regional alterations resolved post-salbutamol.