Nanoparticle dose enhancement and 3-D dosimetric verification of synchrotron microbeam radiation
Creators: name: Gagliardi, Francis
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 321110
subject: Radiation therapy

description: Radiation therapy is a medical treatment technique that utilises ionising radiation to treat disease. Modern linear accelerators equipped with advanced imaging capabilities have transformed radiation therapy into a highly accurate and invaluable treatment modality for cancer patients. However the dose to the target is always limited to the amount of dose that the surrounding healthy tissue can receive. The dose to healthy tissue must remain less than the toxicity threshold for healthy tissue whilst attempting to deliver a tumourcidal dose to the target. A higher irradiation dose would be desirable to stop tumour growth or eliminate tumour cells however unwanted toxicity to the patient is not preventable using conventional radiotherapy.

Microbeam radiation therapy is an experimental form of radiation therapy treatment under development at synchrotrons worldwide. Microbeam radiation therapy uses the principle of spatial fractionation where submillimetric beams provide an effective means to destroy tumour cells whilst sparing the surrounding healthy tissue, in contrast to conventional radiation therapy which uses the principle of temporal fractionation to spare healthy tissue. The delivered dose of radiation using microbeam radiation therapy techniques can be orders of magnitude higher than can be delivered using conventional radiation therapy whilst reducing the toxicity to healthy tissue.

However microbeam radiation therapy has two fundamental issues that need addressing to optimise and accurately deliver treatments to patients. One issue arises from the use low energy (kV) synchrotron generated x-rays compared to conventional radiation therapy using a high energy (MV) linear accelerator, which is the attenuation of low energy x-rays is greater whilst travelling through tissue and bone resulting in a significant reduction of the dose reaching the tumour.

The addition of high atomic number materials in the tumour however may overcome the attenuation of dose by exploiting the dose enhancement effect. The dominant scattering process in the kV energy range is the photoelectric effect which strongly depends on the atomic number of the absorbing material to produce photoelectrons and Auger electrons. Therefore high atomic number materials can provide the means to increase the delivered dose to the tumour volume without increasing the dose to the healthy tissue.

The second issue concerning microbeam radiation therapy is the complexity of microbeam dosimetry. Conventional radiotherapy has clearly defined international dosimetry protocols for low, medium and high energy x-rays however microbeam dosimetry presents many technical limitations due to the size of the microbeams. Verification of the Monte Carlo and dose calculation models for synchrotron microbeams is essential before any treatment planning system calculations can be used for patient treatments.

The radiosensitive PRESAGE® dosimeter has the potential to perform dosimetric verification on microbeams using high resolution imaging techniques. The radiosensitive PRESAGE® dosimeter is a clear polyurethane resin which contains leuco dye and halocarbon radical initiators. When the dosimeter is exposed to radiation, free radicals are generated from the radical initiator and oxidise the leuco dye resulting in a visible colour change within the dosimeter.

The aim of the work undertaken in this thesis was to determine the level of absorbed dose enhancement by inclusions of gold and bismuth based nanoparticle (NP) compounds in synchrotron generated microbeams. To achieve this, radiochromic PRESAGE® dosimeters were fabricated with their radiological properties validated over a suitable energy range for microbeam radiation therapy. The radiological response was found to be within 1 - 2% compared to ion chamber measurements and Monte Carlo simulations for synchrotron beams.

The dose response, stability, useful dose range and post-irradiation protocols were then established to perform synchrotron dosimetry. The dose response was approximately linear up to 200 Gy and stable from 30 minutes to 21 days when stored at -18oC post-irradiation. 
 The physical absorbed dose enhancement due to Au and Bi NPs was measured for superficial (SXRT) and MV radiation along with the first experimental evidence of physical absorbed dose enhancement in a synchrotron x-ray beam. The measured dose enhancements were 16 - 21% for SXRT, 4 - 5% for MV and 22 - 32% for synchrotron irradiations at the maximum concentrations used for the Au and Bi NPs.

Unprecedented 3D high resolution images of microbeam arrays were produced using confocal laser scanning microscopy (CLSM) on irradiated PRESAGE® dosimeters even allowing the visualisation of complex cross-fired and interspersed microbeam radiation therapy arrays. The exceptional spatial resolution of the CLSM images enabled precision measurements to be performed for positional accuracy of the sample stage goniometer on the IMBL. 

Innovations to the CLSM scanning technique on irradiated PRESAGE® dosimeters established a method to perform novel dosimetric evaluation of synchrotron generated broad beams and microbeams which also served as an independent dosimetric verification tool for MC calculations. The previously elusive microbeam peak and valley PDDs and the corresponding variation of PVDR with depth were measureable from a single irradiation in a PRESAGE® dosimeter using the technique developed in this work. The quantification of valley dose with depth is important in determining the normal tissue tolerance and maximum peak dose that can be delivered for MRT.

Ultimately the measurement of the physical absorbed dose enhancement of SSRT and MRT beams by the inclusion of Au and Bi NPs was facilitated utilising the improved CLSM technique and compared to Monte Carlo simulations. Dose enhancements of up to 29 % were measured for synchrotron broad beams and up to 19 % for microbeams. The significance in demonstrating and quantifying the physical absorbed dose enhancement in microbeams is that an increase in dose deliverable to a tumour at depth will be beneficial in future patient treatments.