Controlled kHz laser-driven electron irradiations for pre-clinical applications

TL;DR

The observed improvement in the survival rate of the zebrafish embryos, combined with unchanged cytotoxicity in the cell cultures, indicates promising results for normal tissue sparing while maintaining anticancer efficacy.

Abstract

We report the first in-air irradiations of biological samples with kHz laser-driven electrons with beam energy 20 MeV, high-energy tail extending to 40 MeV, and average dose rate up to 30 Gy/min. An in-house procedure has been developed to characterize and deliver on-demand (i.e. pre-agreed date and time) the target electron beam energy, dose and dose uniformity. We present a tolerance analysis on the laser electron parameters, highlighting the importance of beam stability for precise irradiations of in vivo zebrafish embryos and in vitro U251 glioblastoma cell line. The observed improvement in the survival rate of the zebrafish embryos, combined with unchanged cytotoxicity in the cell cultures, indicates promising results for normal tissue sparing while maintaining anticancer efficacy. The pre-clinical results of this work represent an important milestone towards the clinical translation of laser-plasma accelerators.

Figures (9)

• Figure 1: Beam time structure. (a) Time structure of electrons accelerated by RF-based technology, where the total dose is given by one or more trains of M pulses, with typical $\mu$s duration and frequency from 1 kHz to 100 Hz, and each pulse is composed of N bunches having individual time duration of a few ps and separated by around 300 ps. In comparison, panel (b) shows the time structure of LWFA-driven electrons where for each laser shot there is an electron beam pulse. (c) Scheme of the LWFA acceleration where a laser pulse (red) drives plasma waves on its wake (plasma density is shown with light to dark blue) in which are accelerated electron beam bunches (green) with $\mu$m transverse size and fs time duration, forming the beam pulse.
• Figure 2: Irradiation geometry. (a) Scheme of the accelerator setup for in-air irradiations, with electron beam size and time duration along the path. In yellow is shown the target sample, typically placed 10-50 cm from the vacuum-air interface. In (b) is shown the relation of electron beam diameters and dose rates. (c) Photo of the in-air table with the target holder and two camera monitoring the Lanex screen attached to the output window. (d) Example of electron beam pointing stability and size observation in real-time during the irradiations with a 1 cm grid and a 2$^{nd}$ calibrated camera. (e) Alignment of the target holder with the main spectrometer camera.
• Figure 3: (a) Beam divergence for x-axis (square, dark blue) and y-axis (circle, light blue) and average pointing stability (red) as a function of the gas target backing pressure. (b) Measured maximum dose/pulse as a function of the gas target backing pressure. With green lines is shown the optimal range of operation. (c) Example of 1D normalized electron beam spectrum averaged over thousands of pulses, measured at 2.2 bar, corresponding to a plasma density of $n_e = 1.8 \times 10^{19} cm^{-3}$.
• Figure 4: Beam stability tolerance on laser parameters. The top panel shows the effect on the beam pointing and beam current for a laser energy drop from 39 mJ (a) to 36 mJ (b), corresponding to $>10\%$ loss in total charge and a shift of 10 mrad. The bottom panel shows the sensitivity on the spectral intensity stability versus the focal spot location inside the gas density profile (c), by scanning the target along the beam direction (z-axis). (d) Optimization of the 1D averaged spectrum in z.
• Figure 5: Beam dose measurement. (a) Scheme of the dose measurement assembly with a gafchromic EBT3 film in between every 10 mm PMMA slab, taken at a distance > 15 cm from the exit viewport. (b) Monte Carlo visualization of dose deposition for an electron pulse of 1 pC, peak energy 20 MeV and 10 MeV energy spread (as in Fig. \ref{['fig:3']}(c)). (c) Averaged percentage depth dose (PDD) curves optimized pre-irradiation (black marker) and validation with the average taken during irradiation days (red marker).