Toward Lung Ventilation Imaging Using Hyperpolarized Diethyl Ether Gas Contrast Agent

Hyperpolarized ¹²⁹Xe gas was FDA-approved as an inhalable contrast agent for magnetic resonance imaging of a wide range of pulmonary diseases in December 2022. Despite the remarkable success in clinical research settings, the widespread clinical translation of HP ¹²⁹Xe gas faces two critical challenges: the high cost of the relatively low-throughput hyperpolarization equipment and the lack of ¹²⁹Xe imaging capability on clinical MRI scanners, which have narrow-bandwidth electronics designed only for proton (¹H) imaging. To solve this translational grand challenge of gaseous hyperpolarized MRI contrast agents, here we demonstrate the utility of batch-mode production of proton-hyperpolarized diethyl ether gas via heterogeneous pairwise addition of parahydrogen to ethyl vinyl ether. An approximately 0.1-liter bolus of hyperpolarized diethyl ether gas was produced in 1 second and injected in excised rabbit lungs. Lung ventilation imaging was performed using sub-second 2D MRI with up to 2×2 mm² in-plane resolution using a clinical 0.35 T MRI scanner without any modifications. This feasibility demonstration paves the way for the use of inhalable diethyl ether as a gaseous contrast agent for pulmonary MRI applications using any clinical MRI scanner.