Early Stage Radiation-Induced Lung Injury Detected Using Hyperpolarized 129Xe Morphometry: Proof-of-Concept Demonstration in a Rat Model

Purpose: Radiation-induced lung injury (RILI) is still the major dose-limiting toxicity related to lung cancer radiation therapy, and it is difficult to predict and detect patients who are at early risk of severe pneumonitis and fibrosis. The goal of this proof-of-concept preclinical demonstration was to investigate the potential of hyperpolarized Xe-129 diffusion-weighted MRI to detect the lung morphological changes associated with early stage RILI. Methods: Hyperpolarized Xe-129 MRI was performed using eight different diffusion sensitizations (0.0-115 s/cm(2)) in a small group of control rats (n = 4) and rats 2 wk after radiation exposure (n = 5). The diffusion-weighted images were used to obtain morphological estimates of the pulmonary parenchyma including external radius (R), internal radius (r), alveolar sleeve depth (h), and mean airspace chord length (L-m). The histological mean linear intercept (MLI) were obtained for five control and five irradiated animals. Results: Mean R, r, and L-m were both significantly different (P<0.02) in the irradiated rats (74 +/- 17 mu m, 43 +/- 12 mu m, and 54 +/- 17 mu m, respectively) compared with the control rats (100 +/- 12 mu m, 67 +/- 10 mu m, and 79 +/- 12 mu m, respectively). Changes in measured L-m values were consistent with changes in MLI values observed by histology. Conclusions: Hyperpolarized Xe-129 MRI provides a way to detect and measure regional microanatomical changes in lung parenchyma in a preclinical model of RILI. (C) 2015 Wiley Periodicals, Inc.