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

Rationale and ObjectivesEmergent 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 MethodsForty-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 (PRMfSAD).ResultsPREFUL 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 PRMfSAD: r = 0.55, p = 0.021; Xrs5 Hz: r = −0.44, p = 0.0046, and AX: r = 0.32, p = 0.044).ConclusionPREFUL-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. 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. 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 (PRMfSAD). 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 PRMfSAD: r = 0.55, p = 0.021; Xrs5 Hz: r = −0.44, p = 0.0046, and AX: r = 0.32, p = 0.044). 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.