Hyperpolarized ¹²⁹Xe MRI and Spectroscopy: Quantitative Measurements, Results, and Emerging Opportunities

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.