Tolerance of mouse cardiac tissue to the maximum dose of FLASH versus conventional radiation

Abstract Background: FLASH radiation (average dose rate: >40 Gy/s) delivers ultrahigh doses of radiation, which are several times higher than the clinically used conventional (CONV) radiation doses (average dose rate: >5 Gy/min). This study aimed to investigate the potential benefits of FLASH radiation therapy and compare the effects of FLASH radiation at the maximum dose and CONV radiation on mouse cardiac tissue. Methods: C57BL/6 mice were divided into three groups: control (0 Gy), FLASH (40 Gy/s), and CONV (0.067 Gy/s). The mice treated with 10 and 20 Gy of CONV or FLASH radiation were euthanized at 6, 12, and 16 months. The effect of FLASH radiation was evaluated by plotting the survival curve of irradiated mice. Radiated cardiac tissues were examined using Masson’s trichrome staining (MT) and immunohistochemistry. Fibrous scar formation and alpha-smooth muscle actin-positive areas were quantitatively evaluated separately in the left ventricle, septum, and right ventricle (RV). Results: Shorter survival was observed in the 20 Gy CONV irradiation group than in the 20 Gy FLASH irradiation group. Histological evaluation revealed higher radiation-induced cardiac fibrosis in the RV of the 20 Gy CONV group than in the control, 10 Gy CONV and FLASH, and 20 Gy FLASH groups ( P <0.05). Conclusions: FLASH radiation was more effective than CONV radiation at higher doses and displayed a protective effect and greater cardiac tissue tolerance. The results of this study will help improve cancer treatment outcomes, reduce radiation side effects, shorten treatment duration, and add to radiation biology literature.