Thèse soutenue au Laboratoire d’Optique Appliquée (École Polytechnique) en 2021
Titre: Application of laser-plasma accelerated beams to high dose-rate radiation biology
Laser-plasma accelerators can produce proton and electron beams with a broad range of spectral and temporal properties. Notably, the extremely short duration of the particle bunch (< ps) allows the reach of extremely high peak dose-rate above 109 Gy/s. The effect of ultra high peak dose-rate irradiation on living matter is still being debated. Few recent studies have shown different radiobiological effects of laser-driven proton beams compared to conventional beams, such as lower immediate nitroxidative stress1 and the oscillation of cell mortality with the proton bunches repetition rate2. In addition, the recent discovery of the FLASH effect3, i.e. an increase of healthy tissue tolerance at high mean dose rate irradiation (>40 Gy/s), has boosted the interest towards high dose-rate sources. The FLASH effect has been observed with both single and multi-pulse irradiation, using various combinations of temporal parameters such as mean dose-rate, peak dose-rate, dose-per-pulse, and repetition rate. The relative importance of such parameters in triggering the FLASH effect as well as the mechanisms that underpin it still need to be elucidated4. In this context, laser-driven particles are important tools to shed some light on the radiobiological impact of the aforementioned parameters since their properties are complementary to those of conventional and FLASH irradiation protocols.
Research conducted during my PhD focused on both laser-driven protons and electrons and tackled some of the challenging aspects related to their application to radiation biology, encompassing the source characterisation, beam transport, dosimetry and dose optimisation5. In this presentation, after an introduction on laser-plasma accelerated beams, I will describe radiation biology experiments with two different beams. I will start by presenting the first dosimetric characterisation of a low-energy, kHz laser-driven electron beam. The attractive property of such beams is the high repetition rate that allows for a higher stability of the delivered dose6. I will then present a radiobiology experiment conducted with protons generated by a low repetition rate (1 shot every ~90 minutes) and high energy-per-pulse laser. With such beams, a dose in the order of 10 Gy can be delivered in a single nanosecond pulse, thus achieving irradiation conditions that are even more extreme than those used in FLASH experiments. The source and transport beamline will be described together with preliminary results on Zebrafish embryos irradiation.
1. Raschke, S. et al. Ultra-short laser-accelerated proton pulses have similar DNA-damaging effectiveness but produce less immediate nitroxidative stress than conventional proton beams. Sci Rep 6, 32441 (2016).
2. Bayart, E. et al. Fast dose fractionation using ultra-short laser accelerated proton pulses can increase cancer cell mortality, which relies on functional PARP1 protein. Sci Rep 9, 10132 (2019).
3. Favaudon, V. et al. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice. Sci. Transl. Med. 6, 245ra93-245ra93 (2014).
4. Wilson, J. D., Hammond, E. M., Higgins, G. S. & Petersson, K. Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool’s Gold? Front. Oncol. 9, 1563 (2020).
5. Cavallone, M. Application of laser-plasma accelerated beams to high dose-rate radiation biology. (Institut Polytechnique de Paris, 2020).
6. Cavallone, M. et al. Dosimetric characterisation and application to radiation biology of a kHz laser-driven electron beam. Appl. Phys. B 127, 57 (2021).
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