Design and Implementation of a Multi-Center Trial of 129Xe Gas Exchange MRI and MRS to Evaluate Longitudinal Progression of COPD.

Abstract

MR imaging holds the potential to enhance drug development efficiency by de-risking early phase studies and increasing confidence in results. It can improve patient selection, increase repeatability, and provide greater sensitivity to change, thereby enabling smaller, faster clinical trials. For trials in the pulmonary space, hyperpolarized ¹²⁹Xe MRI is appealing because it provides 3-dimensional imaging of pulmonary ventilation and gas exchange in a brief, non-invasive exam. Metrics derived from ¹²⁹Xe MRI may be more sensitive to disease progression than conventional lung function assessments and may thus provide a valuable means to evaluate numerous novel pharmacologic and biologic therapies now in development. However, despite the acute need for better patient selection and for prognostic and monitoring biomarkers, ¹²⁹Xe MR imaging is not yet widely utilized in pulmonary drug development, partly because such trials must be conducted at multiple centers to enroll enough participants. Thus, incorporating ¹²⁹Xe MRI requires broader dissemination, harmonized image acquisition protocols, standardized dose delivery, visualization, and quantification. Multi-site trials must also be able to operate across all major MRI vendor platforms and diverse software/hardware revisions. To this end, the ¹²⁹Xe MRI Clinical trials consortium has published a harmonized protocol describing four recommended acquisitions. Here we report on the first industry-sponsored study to deploy this ¹²⁹Xe MRI/MRS protocol in a multi-center, multi-platform, multi-national study to evaluate longitudinal progression of chronic obstructive pulmonary disease (COPD). We demonstrate the steps necessary to implement standardized ¹²⁹Xe-MRI acquisition techniques across multiple sites and discuss the practices implemented, quality control approaches, and lessons learned for facilitating and accelerating the implementation of future trials that incorporate this technology. Level of Evidence: 5.