Hyperpolarized xenon 129 (129Xe) MRI uses inhaled 129Xe gas to visualize pulmonary function and microstructure. This review aims to summarize established and emerging quantitative measurements derived from 129Xe MRI and MR spectroscopy (MRS) and illustrate their clinical applications in the characterization and management of cardiopulmonary diseases. They are well tolerated by adults and children with pulmonary disease, employ no ionizing radiation, and their measurements have been validated by correlation with pulmonary function tests in various cardiopulmonary diseases. 129Xe fills unobstructed airspaces, producing three-dimensional maps of ventilation and enabling quantification of ventilation defects, dynamics, and heterogeneity. Leveraging 129Xe's biologic solubility, gas exchange imaging and spectroscopy allow for quantification of gas transfer between airspaces, alveolar membrane, and red blood cells and are sensitive to blood oxygenation and vascular remodeling. Diffusion-weighted imaging quantifies airspace enlargement, providing models of alveolar microstructure. 129Xe MRI can help detect early-stage disease, adding value where reference-standard tools, such as pulmonary function tests, lack sensitivity. The ability of 129Xe MRI to assess function regionally creates opportunities for the detection of localized functional deficits and the improvement of image-guided interventions. Applications of 129Xe MRI and MRS include planning treatment, monitoring disease progression and treatment response, and developing surrogate endpoints for clinical and therapeutic studies. Keywords: MR Imaging, MR Spectroscopy, Thorax, Lung, Hyperpolarized 129Xe, MRI, MRS, Lung Function, Ventilation, Gas Exchange, Alveolar Microstructure © RSNA, 2025.
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