Linking Ventilation Heterogeneity Quantified via Hyperpolarized 3He MRI to Dynamic Lung Mechanics and Airway Hyperresponsiveness.

Advancements in hyperpolarized helium-3 MRI (HP 3He-MRI) have introduced the ability to render and quantify ventilation patterns throughout the anatomic regions of the lung. The goal of this study was to establish how ventilation heterogeneity relates to the dynamic changes in mechanical lung function and airway hyperresponsiveness in asthmatic subjects. In four healthy and nine mild-to-moderate asthmatic subjects, we measured dynamic lung resistance and lung elastance from 0.1 to 8 Hz via a broadband ventilation waveform technique. We quantified ventilation heterogeneity using a recently developed coefficient of variation method from HP 3He-MRI imaging. Dynamic lung mechanics and imaging were performed at baseline, post-challenge, and after a series of five deep inspirations. AHR was measured via the concentration of agonist that elicits a 20% decrease in the subject's forced expiratory volume in one second compared to baseline (PC20) dose. The ventilation coefficient of variation was correlated to low-frequency lung resistance (R = 0.647, P < 0.0001), the difference between high and low frequency lung resistance (R = 0.668, P < 0.0001), and low-frequency lung elastance (R = 0.547, P = 0.0003). In asthmatic subjects with PC20 values <25 mg/mL, the coefficient of variation at baseline exhibited a strong negative trend (R = -0.798, P = 0.02) to PC20 dose. Our findings were consistent with the notion of peripheral rather than central involvement of ventilation heterogeneity. Also, the degree of AHR appears to be dependent on the degree to which baseline airway constriction creates baseline ventilation heterogeneity. HP 3He-MRI imaging may be a powerful predictor of the degree of AHR and in tracking the efficacy of therapy.