Author: Ashok Bhandari, Andrew Joseph Fanning, Kyle J. Gallagher, Brendan Graff, Christopher Jenkins, Kyuhak Oh, Ying Yan, Su-Min Zhou 👨🔬
Affiliation: University of Nebraska Medical Center 🌍
Purpose: This study aimed to design a robust experimental setup to ensure accurate dose delivery using ultra-high-dose-rate for small animal experiments by conducting dosimetric evaluations prior to and during our mice study that explored normal tissue-sparing effects of FLASH.
Methods: Non-sedated C57BL/6 mice were irradiated whole-body with conventional (CONV) and FLASH 16MeV electron beams at 0, 4, 8, and 12Gy using the electron FLEX™ system for investigating the normal tissue-sparing effects (LD50/30). A custom-designed 3D-printed mouse holder securely positioned mice during irradiation. EBT-XD film was used to measure absorbed dose, positioned at the top and bottom of the mouse holder. Prior dosimetric evaluation was done using a custom 3D-printed mouse phantom with slits to contain film at various depths. A prototype FLASH ionization chamber was positioned at the base of the holder for further dose verification. Electron Monte Carlo was used to verify the beam uniformity using a commissioned commercial treatment planning system (TPS).
Results: At 2.5cm depth (top of mouse holder), measured doses for 4, 8, and 12Gy were 3.81±0.06Gy (-4.8%), 7.64±0.09Gy (-4.5%), and 11.48±0.17Gy (-4.3%) for CONV and 3.96±0.08Gy (-1.0%), 8.02±0.08Gy (+0.3%), and 12.36±0.07Gy (+3.0%) for FLASH. The percent dose difference from the expected value averaged ~5%. The TPS calculations further validated the beam uniformity across the mouse holder for both beams. Mice receiving 12Gy whole-body irradiation experienced >20% weight-loss within 6–8 days for both beams. At 8Gy, CONV-irradiated mice exhibited more severe symptoms, including lethargy, hunched posture, and hair graying compared to FLASH-irradiated mice. The estimated LD50/30 for both beams ranged from 8–12Gy, warranting follow-up studies for precise determination.
Conclusion: Preclinical dosimetric evaluations using 3D-printed settings ensured accurate dose delivery for FLASH experiments as well as in-vivo dosimetry during the experiments. This dosimetric validation serves as a framework for supporting reliable investigations of the FLASH effect.