Dosimetric calibration of an anatomically specific ultra-high dose rate electron irradiation platform for preclinical FLASH radiobiology experiments

We characterized the dosimetric properties of a clinical linear accelerator configured to deliver ultra-high dose rate (UHDR) irradiation to mice and cell-culture FLASH radiobiology experiments. UHDR electron beams were controlled by a microcontroller and relay interfaced with the respiratory gating system. We produced beam collimators with indexed stereotactic mouse positioning devices to provide anatomically specific preclinical treatments. Treatment delivery was monitored directly with an ionization chamber, and charge measurements were correlated with radiochromic film at the entry surface of the mice. The setup for conventional (CONV) dose rate irradiation was similar but the source-to-surface distance was longer. Monte Carlo simulations and film dosimetry were used to characterize beam properties and dose distributions. The mean electron beam energies before the flattening filter were 18.8 MeV (UHDR) and 17.7 MeV (CONV), with corresponding values at the mouse surface of 17.2 MeV and 16.2 MeV. The charges measured with an external ion chamber were linearly correlated with the mouse entrance dose. Use of relay gating for pulse control initially led to a delivery failure rate of 20% ($+/-$ 1 pulse); adjustments to account for the linac latency improved this rate to <1/20. Beam field sizes for two anatomically specific mouse collimators (4x4 $cm^2$ for whole-abdomen and 1.5x1.5 $cm^2$ for unilateral lung irradiation) were accurate within <5% and had low radiation leakage (<4%). Normalizing the dose at the center of the mouse (~0.75 cm depth) produced UHDR and CONV doses to the irradiated volumes with >95% agreement. We successfully configured a clinical linear accelerator for increased output and developed a robust preclinical platform for anatomically specific irradiation, with highly accurate and precise temporal and spatial dose delivery, for both CONV and UHDR applications.
Comment: Jinghui Wang and Stavros Melemenidis are co-first authors, and Emil Sch\"uler and Peter G. Maxim are co-senior/co-corresponding authors