Next-generation Lasers for Enabling Ultrafast Functional Pulmonary MRI

PROJECT SUMMARY (30-line limit) Deadly lung diseases such as chronic obstructive pulmonary disease, asthma, lung injury, constrictive bronchiolitis, and pulmonary fibrosis affect >300 million people worldwide and cause ~3 million annual deaths. Moreover, the COVID-19 pandemic and the lingering effects of Long COVID have exacerbated lung disease

morbidity and mortality. Indeed, 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, Positron Emission Tomography, which collectively enable early detection, diagnoses, and

monitoring response to treatment. Pulmonary functional MRI using hyperpolarized Xenon-129 gas was FDA approved in December 2022 because it enables 3D imaging of lung function on a single breath hold and reports on regional lung ventilation, diffusion, and gas exchange. Despite effectiveness and safety of hyperpolarized

Xenon-129 gas MRI to diagnose a wide range of lung diseases, widespread clinical adaptation of this imaging modality faces 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 (and frequent point of

failure) 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 ~0.3-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 ~0.02 nm – an order-of-magnitude improvement

over current-generation systems. 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! If successful, this innovation should lead to the development of substantially more efficient and easier-to-site

hyperpolarization instrumentation for clinical-scale production of hyperpolarized Xenon-129 contrast agent. Here, we propose to explore and characterize the Xenon-129 hyperpolarization performance of this next- generation laser technology. We will investigate the utility of tunable laser bandwidth – in addition to tunable

wavelength and laser power – for increasing the overall efficiency of our commercialized clinical-scale hyperpolarizer device, with the long-term goal of improving the biomedical community’s access to hyperpolarized Xenon-129 gas contrast agent for functional pulmonary imaging.