Feasibility assessment of using oxygen-enhanced magnetic resonance imaging for evaluating the effect of pharmacological treatment in COPD

• We investigate physiologic response to standard COPD treatment regimes using OE-MRI.
• We assess the potential role of OE-MRI in future drug development studies.
• In COPD, OE-MRI parameters showed response to single-dose formoterol.
• OE-MRI parameters showed response to 8-week formoterol/budesonide treatment.
• OE-MRI measurements are feasible in a small-scale multi-center trial setting.

ObjectivesOxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests.Materials and methodsCOPD patients (n = 40), mean FEV1 58% predicted normal, received single-dose inhaled formoterol 9 μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler® 320/9 μg or formoterol Turbuhaler®. OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function.ResultsOE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p < 0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p < 0.05) and increased oxygen extraction from the lung by 58% (p < 0.01). Single-dose formoterol increased both lung wash-out time (+47%, p < 0.05) and lung oxygenation time (+47%, p < 0.05). FEV1 was improved by single-dose formoterol (+12%, p < 0.001) and 8 weeks of budesonide/formoterol (+ 18%, p < 0.001), consistent with published studies.ConclusionsIn COPD, OE-MRI parameters showed response to both single-dose bronchodilatory effects of a β2-agonist, formoterol, and 8-week treatment with an inhaled corticosteroid, budesonide, and the measurements are feasible in a small-scale multi-center trial setting.