PurposeUltra-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.ApproachThirty 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 (VT).ResultsRadiation 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 VT, 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.ConclusionsRespiratory-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 VT (30-Gy FLASH-RT) compared with the control.
Ultra-high dose-rate radiotherapy (FLASH-RT) shows the potential to eliminate tumors while sparing healthy tissues. Current FLASH-RT preclinical animal studies either euthanize animals for histological assessment or use blood tests and cytokine assays to evaluate normal tissue complications. Assessing the progression of complications in situ in live animals with a non-invasive, high-resolution, and sensitive diagnostic method is desired. This study demonstrated using in vivo respiratory-gated micro-computed tomography (micro-CT) to characterize the progression of irradiation-induced pulmonary complications caused by conventional and FLASH-RT in free-breathing mice. Twelve healthy male C57BL/6 mice completed baseline micro-CT scans. Mice were equally separated into three groups that received different treatments targeting the lungs. Treatments administered included no irradiation, 10 MV x-ray FLASH-RT, and 10 MV conventional radiotherapy with a single fraction 15 Gy prescribed dose. Post-treatment, chest cavities of mice were imaged by noninvasive in vivo prospective respiratory-gated micro-CT at 2, 4, 6, 9, and 12 weeks. The image acquisition was triggered using the measured respiratory signal to produce images representing end expiration and peak inspiration. Lung volume and lung CT number were measured for both respiratory phases to evaluate functional residual capacity and tidal volume. Micro-CT images revealed that two mice developed pneumonitis post-treatment after receiving radiotherapy. Here we demonstrated an imaging method to characterize the progression of radiation-induced pulmonary side effects in free-breathing animals.
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