Application of Fluorescent Nuclear Track Detectors for Cellular Dosimetry in Ion Beam Radiotherapy

Ion beam radiotherapy (IBRT) offers a more conformal dose distribution and an enhanced relative biological effectiveness (RBE) in the Bragg peak region as compared to conventional photon therapy. This enhanced RBE is due to the highly localized energy deposition pattern of ion beams, which due to its stochastic nature, is subject to large fluctuations on cellular and sub-cellular scales, resulting in a large variation of biological response in cells exposed to the same beam.Therefore, a cell hybrid detector capable of quantifying local energy deposition at such microscopic scales and correlating it to a biological response is highly desirable. For this purpose, Fluorescent Nuclear Track Detectors (FNTDs) covered with cells have been shown to be an effective cell-hybrid detector, as they can provide information on individual cellular energy deposition with the ability to directly visualize cellular response. In this thesis, a new framework, referred to as the "Cell Dose" model, was established to define dosimetric quantities relevant for quantifying energy deposition at sub-cellular scales, that can be measured with FNTDs as a model detector: specific dose and specific LET. When energy deposition inside the cell nuclei is of interest, the "Cell Dose" quantities can complement the microdosimetric and macroscopic quantities as intermediate quantities between the two. The theoretical framework includes a sampling method that incorporates uncertainties due to five different sources of variations: cross-sectional area of the nuclei, number of particles entering the cell nucleus, the chord lengths of the particles inside the cell nucleus, the linear energy transfer (LET) of the individual particle, and the energy loss straggling of the particles inside the cell nucleus. The distribution of the new dosimetric terms specific dose and specific LET in the cell-wide population was studied for different ions and energies at different depths of their depth-dose profiles, and the individual contribution of these different sources was assessed. The results indicated that there is a great variation (24-55 %) in terms of energy deposition in the cell nuclei, with LET variation of the particles as the major contributor. It was shown that with the use of microscopy and FNTDs, the uncertainty in measurement can potentially be reduced down to only 4-14 %. Furthermore, these dosimetric quantities were compared to experimental results with FNTDs which indicated the possibility of correlating the physical parameters, obtained from FNTDs, to different biological response parameters. With additional improvements and studies, the new "Cell Dose" model may be a valuable tool in radiobiological studies with ion beams, as it can provide valuable information to better understand the underlying physical nature of ion beams in producing cellular response