Dosimetry in synchrotron microbeam radiation therapy

Microbeam Radiation Therapy (MRT) is a novel radiation therapy modality currently developed at several synchrotron sources around the world. The MRT technique is based on the use of plane parallel arrays of microbeams produced by a multislit collimator (MSC). The major benefit of MRT lies in the dose volume effect: a higher radiation tolerance of the normal tissue when using micrometer scale beam size. Moreover, pre-clinical studies highlighted the detrimental effect of MRT on the tumor tissue and demonstrated the presence of a differential effect between normal and tumor tissue. One of the possible application of MRT is the treatment of inoperable paediatric brain tumors where conventional radiotherapy presents a high level of toxicity on the developing brain. Despite the numerous pre-clinical studies that demonstrated the efficiency of the MRT technique over the last twenty years, efforts are still required for the dosimetry quality assurance (QA) before being able to move from pre-clinical to human clinical stage and are the framework of this study. Currently, a 3 generation synchrotron X-ray source is required to perform MRT irradiations. Indeed, the low beam divergence allows the production of plane parallel microbeams, the high dose rates ensure fast irradiation times thus avoiding any blurring of the microbeams with cardiosynchronous motion and the energy spectrum in the range 27-600 keV provides sharp beam penumbra. Quality Assurance (QA) is required for MRT but remains a challenging task due to the high spatial resolution and the radiation resistance properties required from the dosimeter. In MRT, QA must include reference dosimetry in a reference broadbeam (i.e. no spatial fractionation of the beam) and the dosimetry of the microbeams. Microbeam dosimetry consists in the experimental determination of the dose in the microbeams (i.e. peak dose), of the dose between the microbeam (i.e. valley dose), of the Peak to Valley Dose Ratio (PVDR) and of the scatter factors. Many detectors have been investigated and led to the conclusion that ionisation chambers (IC) and Gafchromic® films currently are the most accurate detectors for broadbeam and microbeam dosimetry respectively. However, due to the high dose rates encountered in MRT, lack in collection efficiency has been observed from the IC leading to significant uncertainties. Moreover, despite their great spatial resolution, Gafchromic® films do not provide sufficient dynamic range to display both peak and valley doses, they are passive detectors and still present too significant reading uncertainties to be used as primary detectors. Within this context, the aim of this study was to improve both broadbeam and microbeam dosimetry at the ID17 biomedical beamline at the ESRF (European Synchrotron Radiation Facility, Grenoble, France) where MRT is developed and to propose the corresponding quality assurance procedures. First, the lack of collection efficiency of the MRT reference IC was addressed by the development a new method based on the measurement of the IC response at different dose rates. This method provides correction factors to be applied to the reference IC and results in the determination of the absolute dose with an accuracy better than ± 5%. In the context of MRT veterinary trials on the ID17 biomedical beamline, an absorbed dose to water protocol has been established within this work. In collaboration with ID17, the Centre for Medical Radiation Physics (University of Wollongong, Australia) developed the X-Tream dosimetry system especially for MRT QA applications. The system relies on a high resolution silicon Single Strip Detector (SSD) for the microbeams acquisition. The X-Tream dosimetry system has been characterised at the ESRF and a particular attention was dedicated to the study of the radiation damage induced into the SSD as well as on the experimental determination of the energy dependence of the device. The ability of the SSD to perform rapid and efficient QA tests prior MRT treatment has been evaluated: in-air measurements of 1D intensity profiles of the synchrotron beam used in MRT were performed in order to assess the alignment of the MSC. The SSD was able to detect small misalignments of the MSC which resulted in changes in the valley shape and on the peak and valley signals. The results obtained by the SSD for the MSC alignment were in agreement with the monitoring IC currently used for this purpose on ID17. An alignment procedure based on the pink-beam imaging modality available at the ESRF has also been developed in order to align the SSD with the MRT beam. The SSD has then been used at the ESRF under reference conditions in order to experimentally determine the PVDRs and scatter factors. For the first time, an active detector has been able to measure both valley and peak signals with the same accuracy leading to a direct determination of the PVDRs in agreement with published results obtained using Gafchromic® films and MC simulations. Finally, preliminary tests have been carried at the Imaging and Medical BeamLine (IMBL) at the Australian Synchrotron (AS) where the microbeam array have been acquired for the first time with an active detector.