Radiation Interactions In Biological Matter - The Physical Roots of Biological Response to Radiation

Abstract

Radiotherapy is a widely used therapeutic tool. Development of new techniques in radiotherapy rely on understanding the initial physical interactions of incident particles in biological matter. The processes that lead to energy deposition and so biological damage need to be understood on a range of scales from bulk energy deposition at the centimetre scale down to the details of ionisation distributions at the nanoscale. Monte Carlo (MC) simulation gives insights into these processes that are otherwise difficult to obtain and that can be used to build models of the fundamental physical mechanisms. The work presented in this thesis consists of the implementation and analysis of three MC simulation studies. The first quantifies the energy deposition and ionisations caused by low energy electrons in a simple compartmentalised cell model and the relative importance of cytoplasmic versus nuclear volume in partitioning ionisation counts. The significant proportion of ionisations found in the cytoplasm indicates the potential importance of extra–nuclear targets in initiating cell death. The second study investigates the accuracy of soft x–ray and alpha microbeams for irradiation of the cytoplasm alone. These simulations show that alpha microbeams can in principle provide an accurate tool for probing extra–nuclear targets, but that in a realistic microbeam model scattering may compromise the cellular targeting. The third study presents simulations that extend our understanding of the impact of nanoparticle enhancement of dose by investigating energy deposition both within and outside a target, with the first detailed consideration of the effect of fluorescence in de–localising dose from the target to surrounding tissue. An important finding is that high atomic number nanoparticles not only enhance dose in the target, but also reduce out–of–target scatter dose, thereby offering a mechanism to reduce margin dose and increase treatment efficacy in radiotherapy applications.