The Sparing Effect of Multibeam Ultra-High Dose-Rate Irradiation on Intestinal Tissue in Mice

The ultra-high dose-rate (UHDR) irradiation reduces normal tissue side effects compared to conventional dose-rate (CDR) irradiation-a phenomenon known as the FLASH effect. However, its clinical translation faces a critical barrier in achieving conformal dose distributions, as the brevity of single-beam UHDR delivery precludes gantry rotation. This necessitates understanding whether the FLASH tissue-sparing effect persists when the total dose is split into multiple beams with short intervals. In this study, mice received multibeam whole-abdominal irradiation using either UHDR or CDR beam. UHDR irradiation was delivered using electron beams at an average dose rate of ≥ 550 Gy/s. Multibeam regimens were delivered with 1-min intervals between each beam. Compared to CDR irradiation, multibeam UHDR irradiation significantly improved survival, as evidenced by higher rates following a regimen of 11 Gy in five beams. Similarly, body weight recovery was better with UHDR irradiation at 8 Gy in two beams than with CDR irradiation at 8 Gy, and intestinal crypt regeneration was greater with UHDR irradiation at 12 Gy in four beams than with CDR irradiation at 12 Gy. In conclusion, this study observed the maintenance of the intestinal FLASH effect in a murine model when irradiation was delivered in multiple beams within the tested per-beam dose range of 2.2-4 Gy. Registry and the Registration No. of the Study/Trial: Not Applicable.