Quantifying Regional Radiation-Induced Lung Injury in Patients Using Hyperpolarized 129Xe Gas Exchange Magnetic Resonance Imaging

Purpose: Radiation-induced lung injury has been shown to alter regional ventilation and perfusion in the lung. However, changes in regional pulmonary gas exchange have not previously been measured. Methods and materials:<bold> </bold>Ten patients receiving conventional radiation therapy (RT) for lung cancer underwent pre-RT and 3-month post-RT magnetic resonance imaging (MRI) using an established hyperpolarized Xe-129 gas exchange technique to map lung function. Four patients underwent an additional 8-month post-RT MRI. The MR signal from inhaled xenon was measured in the following 3 pulmonary compartments: the lung airspaces, the alveolar membrane tissue, and the pulmonary capillaries (interacting with red blood cells [RBCs]). Thoracic H-1 MRI scans were acquired, and deformable registration was used to transfer Xe-129 functional maps to the RT planning computed tomography scan. The RT-associated changes in ventilation, membrane uptake, and RBC transfer were computed as a function of regional lung dose (equivalent dose in 2-Gy fractions). Pearson correlations and t tests were used to determine statistical significance, and weighted sum of squares linear regression subsequently characterized the dose dependence of each functional component. The pulmonary function testing metrics of forced vital capacity and diffusing capacity for carbon monoxide were also acquired at each time point. Results:<bold> </bold>Compared with pre-RT baseline, 3-month post-RT ventilation decreased by an average of -0.24 +/- 0.05%/Gy (rho = -0.88; P < .001), membrane uptake increased by 0.69 +/- 0.14%/Gy (rho = 0.94; P < .001), and RBC transfer decreased by -0.41 +/- 0.06%/Gy (rho = -0.92; P < .001). Membrane uptake maintained a strong positive correlation with regional dose at 8 months post-RT, demonstrating an increase of 0.73 +/- 0.11%/Gy (rho = 0.92; P = .006). Changes in membrane uptake and RBC transfer appeared greater in magnitude (%/Gy) for individuals with low heterogeneity in their baseline lung function. An increase in whole-lung membrane uptake showed moderate correlation with decreases in forced vital capacity (rho = -0.50; P = .17) and diffusing capacity for carbon monoxide (rho = -0.44; P = .23), with neither correlation reaching statistical significance. Conclusions: Hyperpolarized Xe-129 MRI measured and quantified regional, RT-associated, dose-dependent changes in pulmonary gas exchange. This tool could enable future work to improve our understanding and management of radiation-induced lung injury.