Description du sujet de thèse

The thesis proposal is situated within the framework of the existing collaboration between the LOA and the Curie Institute (IC), focusing on the biological effects of VHEEs (Very High Energy Electrons) and high dose rates. An experimental irradiation station, capable of applying VHEE electrons in a controlled manner, has been developed at LOA, using the "Salle Jaune" laser with a repetition rate of 1 Hz. The use of this irradiator has enabled a wide-ranging exploration of the effects of VHEEs on living organisms, from cell cultures (in vitro) to mouse organs (ex vivo, using the technique and in comparison with M. Dubail et al.[1], as well as the exploration of in vivo side effects, following the protocol defined by V. Favaudon et al.[2], which notably led to the discovery of the FLASH effect.
Based on the current experimental evidence, a differential toxicity effect seems to exist depending on the irradiation rate, while all other indicators seem to confirm the results of similar studies using conventional accelerators. With the aim of defining the medical relevance of irradiation conditions accessible by VHEEs, further advancements are necessary regarding limitations (control, uniformity), as well as an extension of the parameter space, particularly in terms of irradiated surface area, average dose rate, and repetition rate. All of these improvements will be possible with the new "Laplace/High-Rate" (LaHC) laser system at LOA, which can operate with a repetition rate of 100 Hz and an average power up to fifty times greater than the Salle Jaune.
This thesis aims to implement, characterize, and utilize the VHEE beam from LaHC, as well as conduct experiments in medical physics and radiobiology. These activities include structuring the VHEE beam (LOA), developing irradiation and dosimetry protocols (LOA, IC), qualifying the beam (LOA, IC), and carrying out radiobiology experiments to extend and transpose existing results at low repetition rates (IC).
These activities are positioned in high-potential fields for both fundamental and applied research in laser-generated plasmas, particle acceleration and detection, physical and biological dosimetry, and the design and construction of experimental systems for applications. Due to its very high average power, the LaHC system will be able to provide irradiation conditions that closely match those targeted in a hospital setting, thus opening up vast prospects in both the scientific and industrial domains.

Bayart, E., A. Flacco, O. Delmas, L. Pommarel, D. Levy, M. Cavallone, F. Megnin-Chanet, E. Deutsch, and V. Malka. “Fast Dose Fractionation Using Ultra-Short Laser Accelerated Proton Pulses Can Increase Cancer Cell Mortality, Which Relies on Functional PARP1 Protein.” Scientific Reports 9, no. 1 (December 2019). https://doi.org/10.1038/s41598-019-46512-1.
Dubail, Maxime, Sophie Heinrich, Lucie Portier, Jessica Bastian, Lucia Giuliano, Lilia Aggar, Nathalie Berthault, et al. “Lung Organotypic Slices Enable Rapid Quantification of Acute Radiotherapy Induced Toxicity.” Cells 12, no. 20 (October 11, 2023): 2435. https://doi.org/10.3390/cells12202435.
Faure, Jérôme, Yannick Glinec, A Pukhov, S Kiselev, S Gordienko, E Lefebvre, J-P Rousseau, F Burgy, and Victor Malka. “A Laser–Plasma Accelerator Producing Monoenergetic Electron Beams.” Nature 431, no. 7008 (2004): 541.
Favaudon, Vincent, Laura Caplier, Virginie Monceau, Frédéric Pouzoulet, Mano Sayarath, Charles Fouillade, Marie-France Poupon, et al. “Ultrahigh Dose-Rate FLASH Irradiation Increases the Differential Response between Normal and Tumor Tissue in Mice.” Science Translational Medicine 6, no. 245 (2014): 245ra93-245ra93. https://doi.org/10.1126/scitranslmed.3008973.
Malka, V. “Electron Acceleration by a Wake Field Forced by an Intense Ultrashort Laser Pulse.” Science 298, no. 5598 (November 22, 2002): 1596–1600. https://doi.org/10.1126/science.1076782.
Ronga, Maria Grazia, Marco Cavallone, Annalisa Patriarca, Amelia Maia Leite, Pierre Loap, Vincent Favaudon, Gilles Créhange, and Ludovic De Marzi. “Back to the Future: Very High-Energy Electrons (VHEEs) and Their Potential Application in Radiation Therapy.” Cancers 13, no. 19 (September 30, 2021): 4942. https://doi.org/10.3390/cancers13194942.
Wilson, Joseph D., Ester M. Hammond, Geoff S. Higgins, and Kristoffer Petersson. “Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?” Frontiers in Oncology 9 (January 17, 2020). https://doi.org/10.3389/fonc.2019.01563.

Contexte de travail

These activities are part of a transdisciplinary project between the Laboratory of Applied Optics (LOA) and the Curie Institute (IC).
The activities will take place at the premises of the Laboratory of Applied Optics (Palaiseau) and the Curie Institute (Orsay campus). The candidate will be involved in experimental activities related to the use of intense lasers, the development, design, construction, and operation of an electron accelerator through laser-plasma interaction, as well as the design, development, and operation of diagnostics for the beam.
Beam utilization activities, particularly for dosimetric characterization and applications in medical physics, as well as preparation, handling, and analysis of biological targets, will be carried out in collaboration with the team at the Curie Institute, under the supervision of Mr. C. Fouillade.

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.

Contraintes et risques

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Informations complémentaires

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