Respiratory-gated micro-computed tomography imaging to measure radiation-induced lung injuries in mice following ultra-high dose-rate and conventional dose-rate radiation therapy

Purpose Ultra-high dose-rate radiotherapy (FLASH-RT) shows the potential to eliminate tumors while sparing healthy tissues. To investigate radiation-induced lung damage, we used in vivo respiratory-gated micro-computed tomography (micro-CT) to monitor mice that received photon FLASH-RT or conventional RT on the FLASH irradiation research station at TRIUMF. Approach Thirty healthy male C57BL/6 mice received baseline micro-CT scans followed by radiation therapy targeting the thorax. Treatments administered included no irradiation, 10-MV photon FLASH-RT, and 10-MV conventional RT with either 15 or 30 Gy prescribed dose. Follow-up micro-CT scans were obtained up to 24 weeks post-irradiation, and histology was obtained at the experimental endpoint. Lung volume and CT number were measured during peak inspiration and end-expiration and used to calculate the functional residual capacity (FRC) and tidal volume (V-T). Results Radiation pneumonitis was observed sporadically in micro-CT images at 9 and 12 weeks post-irradiation. Fibrosis was observed in the endpoint images and confirmed with histology. Compared with the 15-Gy treatment groups and unirradiated controls, the micro-CT images for 30-Gy FLASH-RT showed differences during peak inspiration, with a significant reduction in V-T, whereas the 30-Gy conventional RT showed differences during end-expiration, with a significant difference in FRC from 15 Gy. Between 12 weeks and the endpoint, the 30-Gy conventional RT group exhibited the largest reduction in lung volume. Conclusions Respiratory-gated micro-CT imaging was sensitive to radiation pneumonitis and fibrosis. Significant differences were seen in functional metrics measured at the endpoint for FRC (both 30-Gy groups) and V-T (30-Gy FLASH-RT) compared with the control.