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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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