3 t mr system

All subjects underwent resting-state fMRI scans using a 3-T MR system (GE EXCITE, Milwaukee, WI, USA) with an eight-channel phased-array head coil. Routine T2-weighted images [repetition time (TR)/echo time (TE)=4680.0 ms/105.2 ms, matrix size=256×256, field of view (FOV)=256×256 mm², and section thickness=5 mm] and T1-weighted images (TR/TE=2360.4 ms/21.9 ms, matrix size=256×256, FOV=256×256 mm², and section thickness=5 mm) were examined by an expert radiologist to exclude the possibility of clinically silent lesions. The fMRI images were obtained using an echoplanar imaging (EPI) sequence with the following parameters: 30 continuous slices with slice thickness=5 mm, TR=2000 ms, TE=30 ms, FOV=240×240 mm², and data matrix=64×64. A total of 205 volumes was acquired for each subject, requiring a total scan time of 410 s. Subjects were instructed to rest with their eyes closed, not to think about anything in particular, and not to fall asleep.

All imaging was completed at the Robarts Research Institute (Western University, London, Canada). ¹H and inhaled hyperpolarised gas (³He and/or ¹²⁹Xe) MR images (3×3×15 mm³) were acquired within 5 min of one another using a 3T MR system (General Electric Health Care, Milwaukee, WI, USA) as previously described [23 (link)]. For all acquisitions, participants were coached to inhale 1 L of gas from functional residual capacity (FRC), and coronal slices were acquired under breath-hold conditions at FRC+1 L. Thoracic computed tomography (CT) was performed at a similar lung volume using a 64-slice Lightspeed VCT system (GE Healthcare) as previously described [23 (link)]. Quantitative MRI analysis was performed by a single trained observer who was blinded to intervention allocation (MM) using semi-automated segmentation and registration software to generate the MRI ventilation defect per cent (VDP) at baseline [31 (link)]. The observer segmented each baseline MRI dataset twice (coefficient of variation 14.9%; intraclass correlation coefficient 0.97, 95% CI 0.93–0.99), and the mean VDP of the two rounds was reported.