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

Abstract

PurposeRadiation-induced lung injury (RILI) has been shown to alter regional ventilation and perfusion in the lung. However, changes in regional pulmonary gas exchange have not previously been measured. MethodsTen patients receiving conventional radiation therapy (RT) for lung cancer underwent pre-RT and 3-month post-RT MRI using an established hyperpolarized-129Xe gas exchange technique to map lung function. Four patients underwent an additional 8-month post-RT MRI. The MR signal from inhaled xenon is measured in three pulmonary compartments: the lung airspaces, the alveolar membrane tissue, and the pulmonary capillaries (interacting with red blood cells, RBCs). Thoracic 1H MRI scans were acquired, and deformable registration was used to transfer 129Xe functional maps to the RT planning CT. 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, EQD2). Pearson correlation 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. Pulmonary function testing (PFT) metrics forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) were also acquired at each timepoint. ResultsCompared to pre-RT baseline, 3-month post-RT ventilation decreased by an average of -0.24±0.05 %/Gy (ρ=-0.88; P<.001), membrane uptake increased by 0.69±0.14 %/Gy (ρ=0.94; P<.001), and RBC transfer decreased by -0.41±0.06 %/Gy (ρ=-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 (ρ=0.92; P=.006). Changes in membrane uptake and RBC transfer appeared greater in magnitude (%/Gy) for subjects with low heterogeneity in their baseline lung function. An increase in whole-lung membrane uptake showed moderate correlation with decreases in FVC (ρ=-0.50; P=0.17) and DLCO (ρ=-0.44; P=0.23), with neither correlation reaching statistical significance. ConclusionHyperpolarized-129Xe 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 RILI.