Recent studies indicate that FLASH irradiation, which involves ultra-high dose rates in a short time window (usually >40 Gy/s in <500 ms), might be equally efficient against tumors but less harmful to healthy tissues, compared to conventional irradiation with the same total dose. Aiming to verify the latter claim for ocular proton radiotherapy, in vivo experiments with mice are being carried out by Charit e-Universit€ atsmedizin Berlin. This work presents the implemented setup for delivering FLASH proton radiation to a single eye of mice at the Helmholtz-Zentrum Berlin f€ ur Materialien und Energie (HZB). Materials and methods: The HZB cyclotron is tuned to provide a high-intensity 68 MeV focused proton beam. Outside the vacuum beamline, the protons hit a single scatterer, which also serves as range shifter, and a rotating modulator wheel, which produces a flat depth-dose distribution. Two transmission ionization chambers in between, read out by fast electronics, are used as dose monitors for triggering an in-vacuum beam shutter, which blocks the beam once the desired dose has been delivered. A collimating aperture shapes the radiation field at the isocenter, which is measured by a radioluminescent screen and a CCD camera. At the same position, a parallel-plate ionization chamber of type Advanced Markus â is used for absolute dosimetry and characterization of the spread-out Bragg peak inside a water phantom. A thin-foil mirror of adjustable tilt in the beam path assists the correct alignment of the target through side illumination. Radiochromic films of type EBT3 are used to supplement the dosimetry and assist the alignment. Results: A dose rate of 75 Gy/s has been measured, delivering within 200 ms 15 Gy (RBE) with a reproducibility better than AE1%. A depth-dose curve with a range of 5.2 mm in water, 0.9 mm distal fall-off (90%-10%), and AE2.5% ripple has been demonstrated, with a PTV of 6.3 mm diameter, 1.7 mm lateral penumbra (90%-10%), 8% uniformity, and 3% symmetry. Conclusions: The implemented setup is able to accommodate ocular irradiation of narcotized mice with protons, targeting selectively the left or the right eye, under conventional and FLASH conditions. Switching between these two modes can be done within half an hour, including the calibration of the dose monitors and the verification of the dose delivery. Further upgrades are planned after the completion of the ongoing experiment.
Background and aimsThe HZB Cyclotron facility is able to deliver proton FLASH irradiation, providing beamtime to Charité – Universitätsmedizin Berlin for in vivo and in vitro experiments. For these studies, a spread-out Bragg peak with a maximum dose rate of 100 Gy/s has been applied within 200 ms at a maximum energy of 68 MeV. Since then, various system upgrades have been implemented with the aim to increase the achieved dose rate and shorten the irradiation time. The involved components and their performance are presented below. MethodsBetween the cyclotron and its injector, an electrostatic deflector has been installed, which is controlled by an FPGA board and acts as an adjustable beam shutter, providing irradiation times down to 1 ms. Within such short durations, the delivered beam intensity can be safely increased without damaging the vacuum window at the beam exit and without reaching the radiation safety limits. The increased dose rates from a mm-focused beam are then measured by an Advanced Markus Chamber (PTW-Freiburg, Germany) and monitored by an in-house developed transparent ionization chamber, connected to a UNIDOS webline electrometer (PTW-Freiburg, Germany). ResultsBoth ionization chambers have shown a linear response with respect to the beam current for dose rates up to 4 kGy/s. An irradiation time of 1 ms has been achieved with a statistical fluctuation of 4%, while the clinical requirement of <2% dose uncertainty can be achieved with irradiation times longer than 2.5 ms. ConclusionsThe updated FLASH capabilities of the HZB Cyclotron enable a reliable delivery, measurement and monitoring of proton dose rates in the order of several kGy/s within few ms. In combination with the available 3D range modulator, the parameter space for systematic clinical experiments is broadened remarkably.
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Background and aims In the pursuit of optimal parameters for FLASH irradiation, all components involved in the beam delivery should be compatible with requirements spread in an extreme and wide unexplored regime. Aiming for minimal total irradiation times with modulated proton beams, which deliver a flat depth-dose distribution along tumors, a static range modulator has been developed to accommodate ultra-short beam durations regardless of their time structure. The design goals were set to match the functionality of the rotating wheel used for in-vivo and in-vitro FLASH investigations at HZB. Methods Having the form of a ridge filter extended to an additional dimension, a hexagonal-pyramid pattern was configured to an incoming beam of 23 MeV energy with > 1 mm radius, in order to create a 6 mm uniform field with a flat dose range of 5 mm at the target. The manufacturing was done with a 3D printer using VeroWhite, a material similar to PMMA. The lateral and distal dose distribution of both modulators were measured using a Markus Chamber (PTW-Freiburg, Germany) in a water phantom and a radioluminescent screen mounted in front of CCD camera, respectively. Results The developed modulator created very flat dose distributions as designed, with negligible differences to the reference rotating wheel. The positioning tolerances were evaluated as relatively relaxed, with offsets of 2 cm and an angle of 5 degrees not compromising the desired performance. Conclusions The developed static modulator allows systematic proton FLASH studies on small organs using a broad range of timing schemes, disentangled from temporal and spatial incoherencies.
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