Commissioning a 250 MeV research beamline for proton FLASH radiotherapy preclinical experiments

Background: The potential reduction of normal tissue toxicities during FLASH radiotherapy (FLASH-RT) has inspired many efforts to investigate its underlying mechanism and to translate it into the clinic. Such investigations require experimental platforms of FLASH-RT capabilities. Purpose: To commission and characterize a 250 MeV proton research beamline with a saturated nozzle monitor ionization chamber for proton FLASH-RT small animal experiments. Methods: A 2D strip ionization chamber array (SICA) with high spatiotemporal resolution was used to measure spot dwell times under various beam currents and to quantify dose rates for various field sizes. An Advanced Markus chamber and a Faraday cup were irradiated with spot-scanned uniform fields and nozzle currents from 50 to 215 nA to investigate dose scaling relations. The SICA detector was set up upstream to establish a correlation between SICA signal and delivered dose at isocenter to serve as an in vivo dosimeter and monitor the delivered dose rate. Two off-the-shelf brass blocks were used as apertures to shape the dose laterally. Dose profiles in 2D were measured with an amorphous silicon detector array at a low current of 2 nA and validated with Gafchromic films EBT-XD at high currents of up to 215 nA. Results: Spot dwell times become asymptotically constant as a function of the requested beam current at the nozzle of greater than 30 nA due to the saturation of monitor ionization chamber (MIC). With a saturated nozzle MIC, the delivered dose is always greater than the planned dose, but the desired dose can be achieved by scaling the MU of the field. The delivered doses exhibit excellent linearity with (Figure presented.) with respect to MU, beam current, and the product of MU and beam current. If the total number of spots is less than 100 at a nozzle current of 215 nA, a field-averaged dose rate greater than 40 Gy/s can be achieved. The SICA-based in vivo dosimetry system achieved excellent estimates of the delivered dose with an average (maximum) deviation of 0.02 Gy (0.05 Gy) over a range of delivered doses from 3 to 44 Gy. Using brass aperture blocks reduced the 80%-20% penumbra by 64% from 7.55 to 2.75 mm. The 2D dose profiles measured by the Phoenix detector at 2 nA and the EBT-XD film at 215 nA showed great agreement, with a gamma passing rate of 95.99% using 1 mm/2% criterion. Conclusion: A 250 MeV proton research beamline was successfully commissioned and characterized. Challenges due to the saturated monitor ionization chamber were mitigated by scaling MU and using an in vivo dosimetry system. A simple aperture system was designed and validated to provide sharp dose fall-off for small animal experiments. This experience can serve as a foundation for other centers interested in implementing FLASH radiotherapy preclinical research, especially those equipped with a similar saturated MIC.