Beam pulse structure and dose rate as determinants for the Flash effect observed in zebrafish embryo

Background and purpose
Continuing recent experiments at the research electron accelerator ELBE at the Helmholtz-Zentrum Dresden-Rossendorf the influence of beam pulse time structure on the Flash effect should be investigated in a zebrafish embryo model.
Materials and methods
The pulse structures of an isochronous and a synchrocyclotron were mimicked at ELBE with mean dose rates of 287 Gy/s and 177 Gy/s and pulse dose rates of 106 Gy/s and 109 Gy/s, respectively; and a macro pulsing for the latter. For comparison, a maximum (mean dose rate 2.5 x 105 Gy/s, pulse dose rate ~109 Gy/s) and a reference (mean dose rate of ~8 Gy/min) regime were applied. Radiation induced changes were assessed in zebrafish embryos over four days post irradiation.
Results
A significant protecting Flash effect with a clear dependence on mean dose rate was revealed for almost all endpoints and all electron pulse regimes relative to the reference. The macro pulse dependent prolongation of treatment time of the synchrotron-like regime reduce the protecting effect compared to the maximum regime delivered at same pulse but higher mean dose rate. The protecting Flash effect of the cyclotron-like regime was confirmed at a clinical isochronous proton cyclotron comparing the effects induced by 300 Gy/s relative to conventional proton beam delivery.
Conclusion
The mean dose rate or treatment time are more important than pulse dose rate for the extent of the normal tissue protecting Flash effect.