Ion dosimetry for radiobiology experiments employing laser-accelerated beams

Abstract

Cell behaviour in ultra-high dose rate environments, characteristic of laser driven ion acceleration, is a largely unexplored field of research, the understanding of which is crucial to the development of an all-optical delivery of ion beams suitable for cancer treatment. In conducting cell experiments to investigate this behaviour, accurate dosimetry is key to an in-depth understanding of the cell reaction to dose deposited via various particle types and energies.

A commonly used dosimeter in ionization experiments is radiochromic film (RCF), as it provides an optical density response proportional to dose. However, it has been found by numerous research groups that this response to dose is different for particles of different types and energies, which is thought to be linked to their linear energy transfer (LET) value.

The main aims of the first experimental chapter in this thesis are to investigate the relationships between particle LET and RCF optical density response to dose delivered by particles accelerated with traditional low dose-rate acceleration mechanisms. These experiments using low energy protons (5 and 10 MeV) and carbon ions (3 and 6 MeV/u) confirm that the higher a particle LET is, the lower the optical density response to the same dose applied compared with a lower particle LET. It was then confirmed in a separate investigation using high energy carbon (45 MeV/u) and oxygen ions (75 MeV/u) that a particle's atomic mass is not a significant parameter affecting the underresponse, which indicates that LET is indeed the main parameter determining RCF response to dose. An analytical investigation was carried out to determine a quantifiable general relationship between RCF optical density response to dose and a particle's LET. Equations were successfully developed for this, which will require experimental verification.

The second experimental chapter presents two radiobiology experiments where cells are exposed to laser-accelerated particles. The dose delivered was measured using RCF, which was calibrated in previous experimental campaigns. CR39, a separate dosimeter, was also utilized in these experiments, but problems with the analysis software did not allow fluence information to be gained. AGO1522 and HUVEC cell lines were exposed to 9.7 MeV protons accelerated by the LULI2000 beamline at the L'Ecole Polytechnique, Paris, and gliblastoma (GBM) stem cells were irradiated by 10 MeV/u Carbon ions accelerated on the Gemini beamline at the Rutherford Appleton Laboratories, Oxford. Multiple biological assays were carried out in both investigations to determine the cell reaction to high dose-rate ion pulses in comparison with previously attained results of low-dose rate ionisations. The Laboratoire pour l'Utilisation des Lasers Intenses (LULI)-based investigation revealed that human fibroblast AGO1522 cells do not respond differently to the laser-accelerated protons compared with x-ray irradiation, but human umbilical endothelial vein (HUVEC) cells are indeed more dose-rate sensitive. It also revealed that for both cell lines, there appears to be a higher degree of early-response damage (up to 1 hour post-irradiation) for the laser-driven protons than for x-rays, although late-response (from 2 hours post-irradiation) appears similar. A stress-induced premature senescence (SIPS) investigation also revealed that laser-driven protons appear to be more effective in inducing premature senescence than x-rays in HUVEC cell lines. Although not all biological data is currently available for the Gemini experiment, the average foci per cell data shows that lasting damage is caused by the 10 MeV/u Carbon irradiation.

Date of Award	Dec 2021
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Engineering & Physical Sciences Research Council & National Physical Laboratory
Supervisor	Marco Borghesi (Supervisor) & Kevin Prise (Supervisor)