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This research explores the ability of PREFUL MRI to measure immediate and sustained effects of tiotropium/olodaterol on lung function in COPD patients.

May 22, 2026Open Access

Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial

Key Points

This research explores the ability of PREFUL MRI to measure immediate and sustained effects of tiotropium/olodaterol on lung function in COPD patients.
Retrospective subanalysis of a randomized, placebo-controlled, crossover trial with open-label extension.
Included 30 patients with moderate-to-severe COPD who completed MRI at 1.5 T.
Used linear mixed-effects models to assess treatment effects and correlations with other measurements.
Significant improvements in FVL-CM by 4.1 percentage points (95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) after single-dose T/O.
PWV decreased by 0.87 m/s (95% CI: −1.26 to −0.48 m/s) following multiple doses.
Correlations between PREFUL MRI parameters and pulmonary function tests were observed, supporting the effectiveness of the MRI approach.

Abstract

Abstract Objectives To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129 Xe MRI measures. Materials and methods Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5 ± 7.7 years; 17 men); 30 completed the MRI extension at 1.5 T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman’s rank and bootstrap 95% confidence intervals (95% CIs). Results PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) ( p < 0.05). PWV decreased after multiple doses (−0.87 m/s, 95% CI: −1.26 to −0.48 m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and 129 Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume ( ρ = 0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and ¹²⁹Xe-derived VDP, apparent diffusion coefficient, and compartment ratios. Conclusion PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation. Key Points Question Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients? Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing. Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized ¹²⁹Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response. Graphical Abstract

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