Next-Generation Enabling Technologies for Ultrafast Functional Pulmonary MRI - PROJECT SUMMARY Deadly lung diseases such as chronic obstructive pulmonary disease, asthma, lung injury, constrictive bronchiolitis, and pulmonary fibrosis affect >300 million people worldwide and cause over 8 million annual deaths. Moreover, the COVID-19 pandemic has exacerbated lung disease mortality. Despite the vast morbidity and mortality of lung diseases, there is currently no widespread clinical imaging modality to perform high- resolution functional lung imaging: CT, conventional MRI, and chest X-ray generally only provide structural images of dense tissues—informing about pathologies like tumors and pneumonia—but yielding little information about lung ventilation, perfusion, alveoli size, gas-exchange efficiency, etc. This state of affairs contrasts with cancer imaging, which includes MRI, CT, ultrasound, mammography, and Positron Emission Tomography, which collectively enable early detection, diagnoses, and monitoring response to treatment. MRI of hyperpolarized xenon-129 gas enables 3D imaging of lung function and reports on regional lung ventilation, diffusion, and gas exchange. Despite remarkable research breakthroughs in this field demonstrating the effectiveness and safety of hyperpolarized xenon-129 gas MRI to detect a wide range of lung diseases and monitor response to treatment, as well as recent FDA approval of xenon-129 gas MRI, the prospects for widespread clinical adaptation of this imaging modality face major translational challenges—including the high cost and complexity of the equipment for production of hyperpolarized xenon-129 gas. The central and most expensive component of a xenon-129 hyperpolarizer device is the high-power laser diode array (LDA) that provides the resonant light used to polarize the xenon-129 spins. Current xenon-129 hyperpolarizers employ lasers with ~0.25-nm bandwidths; although a significant improvement from the multi-nanometer linewidths of previous un-narrowed LDAs, it is still several- fold wider than the intrinsic linewidths of atomic absorption lines. This mismatch often results in most of the laser light being wasted. Next-generation lasers have recently become available that can provide unprecedented control of the LDA bandwidth down to ~0.07 nm—a four-fold improvement over current-generation systems as proposed in this project. This advance allows the laser output to be matched to the narrow atomic absorption lines, potentially enabling the xenon-129 hyperpolarization efficiency to be improved by several fold! Here, we propose to develop this next-generation laser technology all the way to the clinical-scale utility. We aim to develop a robust, easy-to-maintain scalable device that will allow reducing the cost of goods by a factor of 3 for a clinical- scale hyperpolarizer, enabling potential savings of tens of millions of dollars per year to the biomedical community. In the long term (5-10 years), this project will substantially improve the biomedical community’s access to hyperpolarized xenon-129 gas contrast agent for functional pulmonary imaging and other emerging applications.
