Translational applications of hyperpolarized 3He and 129Xe

Clinical magnetic resonance imaging of the lung is technologically challenging, yet over the past two decades hyperpolarized noble gas ((3)He and (129)Xe) imaging has demonstrated the ability to measure multiple pulmonary functional biomarkers. There is a growing need for non-ionizing, non-invasive imaging techniques due to increased concern about cancer risk from ionizing radiation, but the translation of hyperpolarized gas imaging to the pulmonary clinic has been stunted by limited access to the technology. New developments may open doors to greater access and more translation to clinical studies. Here we briefly review a few translational applications of hyperpolarized gas MRI in the contexts of ventilation, diffusion, and dissolved-phase imaging, as well as comparing and contrasting (3)He and (129)Xe gases for these applications. Simple static ventilation MRI reveals regions of the lung not participating in normal ventilation, and these defects have been observed in many pulmonary diseases. Biomarkers related to airspace size and connectivity can be quantified by apparent diffusion coefficient measurements of hyperpolarized gas, and have been shown to be more sensitive to small changes in lung morphology than standard clinical pulmonary functional tests and have been validated by quantitative histology. Parameters related to gas uptake and exchange and lung tissue density can be determined using (129)Xe dissolved-phase MRI. In most cases functional biomarkers can be determined via MRI of either gas, but for some applications one gas may be preferred, such as (3)He for long-range diffusion measurements and (129)Xe for dissolved-phase imaging. Greater access to hyperpolarized gas imaging coupled with newly developing therapeutics makes pulmonary medicine poised for a potential revolution, further adding to the prospects of personalized medicine already evidenced by advancements in molecular biology. Hyperpolarized gas researchers have the opportunity to contribute to this revolution, particularly if greater clinical application of hyperpolarized gas imaging is realized.