Imaging Iodine-125 requires an increased focus on developing an understanding of how fundamental processes used by imaging systems work to provide quantitative output for the imaging system. Isotopes like I-125 pose specific imaging problems that are a result of low energy emissions as well as how closely spaced those emissions are in the spectrum. This work seeks to characterize the performance of a small animal SPECT-CT imaging system with respect to imaging I-125 for use in a preclinical translational research environment and to understand how the performance of this system relates to critical applications such as attenuation and scatter correction. The specific aims of this work examined several key areas of system function and performance with respect to I-125 imaging. The first aim examined the geometric SPECT calibration routine used for the Inveon imaging system with a particular focus on determining the accuracy of the calibration as well as the robustness of the algorithm under routine and adverse imaging conditions. The second aim was to characterize detector uniformity issues that may arise by comparing the uniformity performance of the system with both I-125 and Co-57 as well as examining the possibility of altering the acquisition method for normalization scans to increase the uniformity performance. The third aim sought to optimize the energy window used for acquisition of I-125 data and to determine the effects the selection of the window had on valid and scatter events. The fourth aim used the optimized windows, determined by the third aim, to assess the performance of a reconstruction algorithm, currently under development, that corrects for attenuation and scatter effects. The fifth and final aim of this work sought to assess the feasibility acquiring SPECT-CT data simultaneously and to assess the quality of data that could be achieved if simultaneous acquisition of the two imaging modalities was, in fact, possible. This work met these aims by performing an extensive series of studies examining the response of the system to I-125 imaging. These included multiple series of phantom imaging using both manufacturer as well as custom-designed sources for use with measurements involving I-125 and Co-57. Statistics from over 60 datasets with analysis in greater than 480 regions of interest were used for the analysis of attenuation and scatter correction data alone. The final study involving simultaneous SPECT-CT acquisition required modification of the imaging hardware to enable this type of data collection as well as development of a reconstruction algorithm to correctly handle the CT data acquired in a step-and-shoot helical mode. A number of key findings resulted from this work including the validation of the calibration routine of this imaging system, even under non-ideal imaging conditions for both the SPECT and CT modalities. Uniformity performance with I-125 was found to be a challenge with this imaging system but reductions in performance compared to other isotopes were not significant enough to introduce severe artifacts into the image data. Optimization of I-125 parameters resulted in improvements of the processed data indicating that the recommended settings provided by the manufacturer could be altered to provide results that better balance between minimizing scatter effects and maximizing detection of valid events. Assessment of the proposed scatter and attenuation correction algorithm for this system showed marked improvement as compared to data processed without these corrections. The final study of simultaneous SPECT-CT imaging proved this acquisition method to be feasible on a commercial system with minimal The primary conclusions drawn from this study indicate that the system is adequate for imaging with I-125 when care is taken to properly maintain the system as well as keeping sources current and properly centered in the scanner field of view during calibration. The study strongly illustrates the necessity of compensating any data collected using I-125 for attenuation and scatter effects; with some regions showing greater than 25% attenuation and approximately 30% improvement in quantitative values for scatter affected regions with the corrections applied. The study also concludes that simultaneous SPECT-CT is feasible with minor adjustments to a commercial platform.

Electron beam therapy planning and custom electron bolus design were identified as areas in which improvements in equipment and techniques could lead to significant improvements in treatment delivery and patient outcomes. The electron pencil beam algorithms used in conventional Treatment Planning Systems do not accurately model the dose distribution in irregularly shaped objects, near oblique surfaces or in inhomogeneous media. For this reason, at Christchurch Oncology Centre the TPS is not relied on for planning electron beam treatments. This project is an initial study of ways to improve the design of custom electron bolus, the planning of electron beam therapy, and other radiation therapy simulation tasks, by developing a system for the accurate assessment of dose distributions under irregular contours in clinically relevant situations. A shaped water phantom system and a diode array have been developed and tested. The design and construction of this water phantom dosimetry system are described, and its capabilities and limitations discussed. An EGS/BEAM Monte Carlo simulation system has been installed, and models of the Christchurch Oncology Centre linacs in 6MeV and 9MeV electron beam modes have been built and commissioned. A test was run comparing the EGS/BEAM Monte Carlo system and the CMS Xio conventional treatment planning system with the experimental measurement technique using the water phantom and the diode array. This test was successful as a proof of the concept of the experimental technique. At the conclusion of this project, the main limitation of the diode array system was the lack of data processing software. The array produces a large volume of raw data, but not enough processed data was produced during this project to match the spatial resolution of the computer models. An automated data processing system will be needed for clinical use of the array. It has been confirmed that Monte Carlo and pencil-beam algorithms predict significantly different dose distributions for an irregularly shaped object irradiated with megavoltage electron beams. The results from the diode array were consistent with the theoretical models. This project was an initial investigation. At the time of writing, the diode array and the water phantom systems were still at an early stage of development. The work reported here was performed to build, test and commission the equipment. Additional work will be needed to produce an instrument for clinical use. Research into electron beam therapy could be continued, or the equipment used to expand research into new areas.

Thesis (M.Sc.)--University of Wollongong, 2005. / Typescript. Includes bibliographical references: leaf 225-238.

Thesis (Ph.D.)--University of Wollongong, 2006. / Typescript. Includes bibliographical references: p. 161-174.

Thesis (M. Sc.)--Carleton University, 2002. / Includes bibliographical references (p. 116-117). Also available in electronic format on the Internet.

Thesis (MSc.-Res.)--University of Wollongong, 2008. / Typescript. Includes bibliographical references: leaf 66-69.

Thesis (M.Sc.) - Carleton University, 2007. / Includes bibliographical references (p. 67-73). Also available in electronic format on the Internet.

Raman microscopy (RM) is a vibrational spectroscopic technique capable of obtaining sensitive measurements of molecular composition, structure, and dynamics from a very small sample volume (~1 µm). In this work, a RM system was developed for future applications in cellular radiobiology, the study of the effects of ionizing radiation on cells and tissues, with particular emphasis on the capability to investigate the internal molecular composition of single cells (10-50 µm in diameter). The performance of the RM system was evaluated by imaging 5 µm diameter polystyrene microbeads dispersed on a silicon substrate. This analysis has shown that RM of single cells is optimized for this system when using a 100x microscope objective and a 50 µm confocal collection aperture. Quantitative measurements of the spatial, confocal, and spectral resolution of the RM system have been obtained using metal nanostructures deposited on a flat silicon substrate. Furthermore, a spectral investigation of several substrate materials was successful in identifying low-fluorescence quartz as a suitable substrate for RM analysis of single cells. Protocols have been developed for culturing and preparing two human tumor cell lines, A549 (lung) and DU145 (prostate), for RM analysis, and a spectroscopic study of these two cell lines was performed. Spectra obtained from within cell nuclei yielded detectable Raman signatures from all four types of biomolecules found in a human cell: proteins, lipids, carbohydrates, and nucleic acids. Furthermore, Raman profiles and 2D maps of protein and DNA distributions within single cells have been obtained with micron-scale spatial resolution. It was also found that the intensity of Raman scattering is highly dependent on the concentration of dense nuclear material at the point of Raman collection. RM shows promise for studying the interactions of ionizing radiation with single cells, and this work has been successful in providing a foundation for the development of future radiobiological RM experiments.

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