A feasibility study of zebrafish embryo irradiation with laser-accelerated protons

Abstract

The development from single shot basic laser plasma interaction research toward experiments in which repetition rated laser-driven ion sources can be applied requires technological improvements. For example, in the case of radio-biological experiments, irradiation duration and reproducible controlled conditions are important for performing studies with a large number of samples. We present important technological advancements of recent years at the ATLAS 300 laser in Garching near Munich since our last radiation biology experiment. Improvements range from target positioning over proton transport and diagnostics to specimen handling. Exemplarily, we show the current capabilities by performing an application oriented experiment employing the zebrafish embryo model as a living vertebrate organism for laser-driven proton irradiation. The size, intensity, and energy of the laser-driven proton bunches resulted in evaluable partial body changes in the small (<1 mm) embryos, confirming the feasibility of the experimental system. The outcomes of this first study show both the appropriateness of the current capabilities and the required improvements of our laser-driven proton source for in vivo biological experiments, in particular the need for accurate, spatially resolved single bunch dosimetry and image guidance.

Radiobiology Experiments With Ultra-high Dose Rate Laser-Driven Protons: Methodology and State-of-the-Art

“…To date no mouse based invivo irradiation has been reported with laser-driven protons, although they can be readily used with the above-mentioned models. The only published evidence of in-vivo research comes from a recent study published by Rösch et al [123]. Due to a good match of the beam spot dimensions of laser-driven protons and the body size of zebrafish embryos, they can be potentially used as suitable in vivo models.…”

Dose-dependent Changes After Proton and Photon Irradiation in a Zebrafish Model

“…Our results prove the value of endpoint refinement for zebrafish embryo system in radiobiology experiments on accelerated particles (46). This reliable, reproducible and easily available in vivo model (47) could be implemented for quantitative analysis of the new particle acceleration and dose delivery methods that yield beams with non-clinical parameters, like the ultrahigh dose rate applied for Flash RT (48).…”

Association of Cancer Stem Cell Radio-Resistance Under Ultra-High Dose Rate FLASH Irradiation With Lysosome-Mediated Autophagy

“…In the last few decades, important progress on laser plasma acceleration provided a new method to study radiobiology effects ( Ledingham et al, 2014 ). The laser-driven ion beams have ultra-short pulse duration in a range of nanoseconds and ultra-high dose rate in the order of 10 9 Gy/s ( Bin et al, 2012 ; Doria et al, 2012 ; Pommarel et al, 2017 ; Hantonl et al, 2019 ), showing the potential for in vitro ( Yogo et al, 2011 ; Zeil et al, 2013 ; Raschke et al, 2016 ; Bayart et al, 2019 ) and in vivo ( Rosch et al, 2020 ) FLASH-RT besides cyclotrons, synchrotrons or synchrocyclotron ( Patriarca et al, 2018 ). Presently, there are few articles on FLASH-RT, mainly because the realization of ultra-high dose rate is quite difficult ( Griffin et al, 2020 ).…”