Expanding dose and dose‐rate capabilities of a synchrotron‐based pre‐clinical proton FLASH irradiation platform

BACKGROUND: Proton FLASH radiotherapy has demonstrated promising normal tissue sparing for similar tumor control at ultra-high dose rates (> 40 Gy/s), but systematic investigation of dose-rate-dependent biological mechanisms is limited. Most existing proton platforms operate within a narrow dose-rate range. Synchrotron-based systems are further constrained by limited beam current and cyclic ("spill-based") delivery. PURPOSE: To develop and validate a synchrotron-based small-animal proton irradiation platform with expanded and controllable dose and dose-rate capabilities, enabling systematic studies across conventional, intermediate (meso)-dose-rate (μDR: 1-40 Gy/s) and FLASH regimes. METHODS: The beamline was redesigned to incorporate three beam modulation modes (low, mid, and high dose) by modifying initial scattering conditions and re-optimizing and repositioning downstream components, including cone-shaped flattening filters, ridge filters, and range compensators. 14 discrete synchrotron beam extraction settings (denoted as "IDs") with different beam fluxes were developed and combined with 3 beam modulation modes, resulting in 42 dose and dose-rate combinations. Ridge filters were fabricated using resin-based 3D printing with an iterative geometric correction workflow. Depth-dose distributions were measured using an Advanced Markus ionization chamber, and lateral dose profiles were verified using radiochromic film. RESULTS: The low-, mid-, and high-dose modes achieved maximum single-spill doses of 20.8 Gy (205 Gy/s), 30.2 Gy (297 Gy/s), and 53.8 Gy (531 Gy/s), respectively. Across all beam IDs and modulation modes, dose rates ranged from approximately 13 Gy/s to 2200 Gy/s, spanning μDR and FLASH regimes. Measured depth-dose profiles agreed with Monte Carlo simulations within ± 4%, and lateral dose flatness was within ± 3.7%. CONCLUSIONS: This modular beamline redesign significantly expands the achievable dose and dose-rate combinations of a synchrotron-based proton irradiation platform without requiring accelerator modifications. The system enables 42 reproducible dose and dose-rate configurations with single-spill delivery, providing a flexible framework for systematic investigation of dose-rate-dependent radiobiological proton FLASH effects.