Thesis (M.Sc. (Res.))--University of Wollongong, 2009. / Typescript. Includes bibliographical references: leaf 69-71.

Thesis (Ph.D)--Mechanical Engineering, Georgia Institute of Technology, 2010. / Committee Chair: Farzad Rahnema; Committee Co-Chair: Eric Elder; Committee Member: C.-K. Chris Wang; Committee Member: Rebecca Howell; Committee Member: Sang Cho. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Covert stroke (CS) comprises lesions in the brain often associated by risk factors such as a diet high in fat, salt, cholesterol and sugar (HFSCS). Developing a rodent model for CS incorporating these characteristics is useful for developing and testing interventions. The purpose of this thesis was to determine if magnetic resonance (MR) can detect brain abnormalities to confirm this model will have the desired anatomical effects. Ex vivo MR showed brain abnormalities for rats with the induced lesions and fed the HFSCS diet. Spectra acquired on the fixed livers had an average percent area under the fat peak relative to the water peak of (20±4)% for HFSCS and (2±2)% for control. In vivo MR images had significant differences between surgeries to induce the lesions (p=0.04). These results show that applying MR identified abnormalities in the rat model and therefore is important in the development of this CS rodent model.

Covert stroke (CS) comprises lesions in the brain often associated by risk factors such as a diet high in fat, salt, cholesterol and sugar (HFSCS). Developing a rodent model for CS incorporating these characteristics is useful for developing and testing interventions. The purpose of this thesis was to determine if magnetic resonance (MR) can detect brain abnormalities to confirm this model will have the desired anatomical effects. Ex vivo MR showed brain abnormalities for rats with the induced lesions and fed the HFSCS diet. Spectra acquired on the fixed livers had an average percent area under the fat peak relative to the water peak of (20±4)% for HFSCS and (2±2)% for control. In vivo MR images had significant differences between surgeries to induce the lesions (p=0.04). These results show that applying MR identified abnormalities in the rat model and therefore is important in the development of this CS rodent model.

This work describes the development and application of a novel combination of single-cell Raman spectroscopy (RS), automated data processing, and principal component analysis (PCA) for investigating radiation induced biochemical responses in human tumour cells. The developed techniques are first validated for the analysis of large data sets (~200 spectra) obtained from single cells. The effectiveness and robustness of the automated data processing methods is demonstrated, and potential pitfalls that may arise during the implementation of such methods are identified. The techniques are first applied to investigate the inherent sources of spectral variability between single cells of a human prostate tumour cell line (DU145) cultured {\it in vitro}. PCA is used to identify spectral differences that correlate with cell cycle progression and the changing confluency of a cell culture during the first 3-4 days after sub-culturing. Spectral variability arising from cell cycle progression is (i) expressed as varying intensities of protein and nucleic acid features relative to lipid features, (ii) well correlated with known biochemical changes in cells as they progress through the cell cycle, and (iii) shown to be the most significant source of inherent spectral variability between cells. This characterization provides a foundation for interpreting spectral variability in subsequent studies. The techniques are then applied to study the effects of ionizing radiation on human tumour cells. DU145 cells are cultured in vitro and irradiated to doses between 15 and 50 Gy with single fractions of 6 MV photons from a medical linear accelerator. Raman spectra are acquired from irradiated and unirradiated cells, up to 5 days post-irradiation. PCA is used to distinguish radiation induced spectral changes from inherent sources of spectral variability, such as those arising from cell cycle. Radiation induced spectral changes are found to correlate with both the irradiated dose and the incubation time post-irradiation, and to arise from biochemical differences in lipids, nucleic acids, amino acids, and conformational protein structures between irradiated and unirradiated cells. This study is the first use of RS to observe radiation induced biochemical effects in single cells, and is the first use of vibrational spectroscopy to observe such effects independent from cell cycle or cell death related processes. The same methods are then applied to a panel of human tumour cell lines, derived from prostate (DU145, PC3, LNCaP and PacMet), breast (MDA-MB-231 and MCF7) and lung (H460), which vary by p53 gene status and intrinsic radiosensitivity. One radiation induced PCA component is detected for each cell line by statistically significant changes in the PCA score distributions for irradiated samples, as compared to unirradiated samples, in the first 24 to 72 hours post-irradiation. These RS response signatures arise from radiation induced changes in cellular concentrations of aromatic amino acids, conformational protein structures, and certain nucleic acid and lipid functional groups. Correlation analysis between the radiation induced PCA components separates the cell lines into three unique RS response categories: R1 (H460, MCF7 and PacMet), R2 (MDA-MB-231 and PC3), and R3 (DU145 and LNCaP). These RS categories partially segregate according to radiosensitivity; the R1 and R2 cell lines are radioresistant and the R3 cell lines are radiosensitive (PacMet radiosensitivity (R1) unknown). The R1 and R2 cell lines further segregate according to p53 gene status, corroborated by cell cycle analysis post-irradiation. Preliminary results obtained from a mouse prostate tumour cell line (TRAMP-C2), irradiated both in vitro and in vivo, indicate that RS signatures of radiation response may also be detectable from tumour cells obtained from an in vivo system during radiation therapy treatment. These results indicate the potential for future RS studies designed to investigate, monitor, or predict radiation response. / Graduate

The ArcCHECK dosimeter is a novel dosimetry tool that uses a helical array of silicon diode detectors to measure dose in a cylindrical plane. 3DVH is an associated software that can use ArcCHECK diode measurements along with treatment planning system (TPS) data to guide a full 3D dose reconstruction. The ArcCHECK phantom, along with 3DVH software was evaluated as a volumetric modulated arc therapy (VMAT) pretreatment verification tool. The comprehensive evaluation of the ArcCHECK and 3DVH system involved a comparison of measured dose to both ECLIPSE and Monte Carlo calculated dose for open fields and intensity modulated radiation therapy (IMRT) plans. System based confidence limits for gamma-pass rate and dose difference metrics were established through the measurement of prostate and head and neck VMAT plans. Using the system based confidence limits and clinically accepted tolerances, the sensitivity of the ArcCHECK and 3DVH system to VMAT errors was determined. Dose measured by the ArcCHECK and reconstructed in 3DVH agreed very well with dose calculated in ECLIPSE and Monte Carlo for both open fields and IMRT plans. The only results that fell outside of clinically accepted tolerances were a set of head and neck IMRT plans, however it was determined that a major factor in this result was suboptimal modelling of MLC effects in the TPS, in combination with changes in linac performance since commissioning of the TPS model. VMAT measured by the ArcCHECK and 3DVH system were in excellent agreement with ECLIPSE results and system based confidence limits were determined to be tighter than commonly used limits. ArcCHECK and 3DVH were sensitive to clinically relevant VMAT errors and insensitive to errors with little dosimetric impact, although diode measurements alone required tighter tolerances than are typically used. The ArcCHECK phantom and 3DVH software when used together have been shown to provide useful dosimetric information when used for VMAT pretreatment verification. / Graduate / 0756

X-ray computed tomography (CT) polymer gel dosimetry (PGD) is an attractive tool for three-dimensional (3D) radiation therapy (RT) treatment verification due to the availability of CT scanners in RT clinics. Nevertheless, wide-spread use of the technique has been hindered by low signal-to-noise CT images largely resulting from gel formulations with low radiation sensitivity. However, a new gel recipe with enhanced dose sensitivity was recently introduced that shows great promise for use with CT readout. This dissertation describes development of an CT PGD system for 3D verification of RT treatments using the new gel formulation. The work is divided into three studies: gel characterization, commissioning of a multislice CT scanner and investigation of a dose rate dependence observed during gel characterization. The first component of this work examines the dosimetric properties of the new gel formulation. The response of the gel is found to be stable between 15 - 36 hours post-irradiation and excellent batch reproducibility is seen for doses between 0 - 28 Gy. A dose rate dependence is found for gels irradiated between 100 - 600 MU/min, indicating machine dose rate must be consistent for calibration and test irradiations to avoid dosimetric error. An example clinical application is also presented using an IMRT treatment verification that demonstrates the potential of the system for use in modern RT. The second component of this work focuses on commissioning a multislice CT scanner for CT PGD. A new slice-by-slice background subtraction technique is introduced to account for the anode heel effect. Additional investigations show recommendations for optimizing image quality in CT PGD using a single slice machine also apply to multislice scanners. In addition, the consistency of CT numbers across the multislice detector array is found to be excellent for all slice thicknesses. Further work is performed to assess the tube load characteristics of the scanner and develop a scanning protocol for imaging large gel volumes. Finally, images acquired throughout the volume of an unirradiated active gel show variations in CT data across each image on the order of 7 HU. However, these variations are not expected to greatly influence gel measurements as they are consistent throughout the gel volume. The third component of this work examines the dose rate dependence found during gel characterization. Studies using gel vials and 1 L cylinders indicate the response of the gel does not depend on changes in mean dose rate on the order of seconds to minutes. However, the machine dose rate remains, indicating variations in dose rate on the order of milliseconds influence the response of the gel. An attempt is made to mitigate the effect by increasing the concentration of antioxidant in the gel system but results in reduced overall response. Further work is performed to determine if self-crosslinking of one of the gel components contributes to the observed machine dose rate dependence. In summary, this dissertation has significantly advanced the field of gel dosimetry by providing a prototype CT PGD system with enhanced dose resolution for complex RT treatment verification. / Graduate / 0992 / 0495 / 0756 / holly.johnston@utsouthwestern.edu

Bibliography: leaves 148-155. / xiv, 210 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis provides several methods for assessment of total machine dependent distortion which allows the clinical significance of that distortion to be established. A method for removal of machine dependent distortions is also presented and shown to work for a locally produced, large field of view spatial linearity phantom. Finally, a possible method is developed which is suitable for application of the distortion correction method to actual patients. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physics and Mathematical Physics, 1997?

Thesis (M.Sc.) - Carleton University, 2008. / Includes bibliographical references (p. 77-81). Also available in electronic format on the Internet.

Thesis (M. Sc.)--Carleton University, 2001. / Includes bibliographical references (p. 79-84). Also available in electronic format on the Internet.