Phase-Resolved Functional Lung (PREFUL) MRI to Quantify Ventilation: Feasibility and Physiological Relevance in Severe Asthma

Abstract

Rationale and objectives: Emergent evidence in several respiratory diseases supports translational potential for Phase-Resolved Functional Lung (PREFUL) MRI to spatially quantify ventilation but its feasibility and physiological relevance have not been demonstrated in patients with asthma. This study compares PREFUL-derived ventilation defect percent (VDP) in severe asthma patients to healthy controls and measures its responsiveness to bronchodilator therapy and relation to established measures of airways disease.

Materials and methods: Forty-one adults with severe asthma and seven healthy controls performed same-day free-breathing ¹H MRI, ¹²⁹Xe MRI, spirometry, and oscillometry. A subset of participants (n = 23) performed chest CT and another subset of participants with asthma (n = 19) repeated ¹H MRI following the administration of a bronchodilator. VDP was calculated for both PREFUL and ¹²⁹Xe MRI. Additionally, the percent of functional small airways disease was determined from CT parametric response maps (PRM_fSAD).

Results: PREFUL VDP measured pre-bronchodilator (19.1% [7.4-43.3], p = 0.0002) and post-bronchodilator (16.9% [6.1-38.4], p = 0.0007) were significantly greater than that of healthy controls (7.5% [3.7-15.5]) and was significantly decreased post-bronchodilator (from 21.9% [10.1-36.9] to 16.9% [6.1-38.4], p = 0.0053). PREFUL VDP was correlated with spirometry (FEV₁%_pred: r = -0.46, p = 0.0023; FVC%_pred: r = -0.35, p = 0.024, FEV₁/FVC: r = -0.46, p = 0.0028), ¹²⁹Xe MRI VDP (r = 0.39, p = 0.013), and metrics of small airway disease (CT PRM_fSAD: r = 0.55, p = 0.021; Xrs_{5 Hz}: r = -0.44, p = 0.0046, and AX: r = 0.32, p = 0.044).

Conclusion: PREFUL-derived VDP is responsive to bronchodilator therapy in asthma and is associated with measures of airflow obstruction and small airway dysfunction. These findings validate PREFUL VDP as a physiologically relevant and accessible ventilation imaging outcome measure in asthma.