A Longitudinal Evaluation of Partial Lung Irradiation in Mice by Using a Dedicated Image-Guided Small Animal Irradiator

Purpose: In lung cancer radiation therapy, the dose constraints are determined mostly by healthy lung toxicity. Preclinical microirradiators are a new tool to evaluate treatment strategies closer to clinical irradiation devices. In this study, we quantified local changes in lung density symptomatic of radiation-induced lung fibrosis (RILF) after partial lung irradiation in mice by using a precision image-guided small animal irradiator integrated with micro-computed tomography (CT) imaging. Methods and Materials: C57BL/6 adult male mice (n=76) were divided into 6 groups: a control group (0 Gy) and groups irradiated with a single fraction of 4, 8, 12, 16, or 20 Gy using 5-mm circular parallel-opposed fields targeting the upper right lung. A Monte Carlo model of the small animal irradiator was used for dose calculations. Following irradiation, all mice were imaged at regular intervals over 39 weeks (10 time points total). Nonrigid deformation was used to register the initial micro-CT scan to all subsequent scans. Results: Significant differences could be observed between the 3 highest (>10 Gy) and 3 lowest irradiation (<10 Gy) dose levels. A mean difference of 120 ± 10 HU between the 0- and 20-Gy groups was observed at week 39. RILF was found to be spatially limited to the irradiated portion of the lung. Conclusions: The data suggest that the severity of RILF in partial lung irradiation compared to large field irradiation in mice for the same dose is reduced, and therefore higher doses can be tolerated