Includes bibliographies. / The use of 1-125 seeds in brachytherapy is widespread and becoming increasingly varied. The spatial dose distributions around two types of 1-125 seeds in general use, were measured using a Geiger-Muller chamber. Seeds with the 1-125 adsorbed onto resin spheres had a 10% less anisotropic dose distribution than seeds containing a silver wire with the 1-125 adsorbed onto it. An interpolative method was developed for fast dose calculations taking this anisotropy into account.

<p>Quantification of the optical properties of superficial biological tissue (e.g. skin on muscle) from spatially resolved reflectance measurements can yield important physiological information. Some examples include the non-invasive measurement of chemotherapy drugs or exogenous chromophores used for photodynamic cancer treatment and the assessment of hemoglobin oxygenation in tissue. Superficial tissue is a multilayered structure with each component having different macroscopic absorption and scattering coefficients, as well as different vascularization and exogenous chromophore pharmacokinetics. A layered model of photon transport is therefore required to match theoretical predictions with experimental measurements. Once a photon transport model is developed, it defines the forward calculation used in the inverse problem of determining the set of tissue optical properties that gives the best fit to experimental data. In the present work the frequency domain (FD) method is employed to probe a two-layer turbid medium. The goal is to improve quantification of superficial tissue optical properties relative to current methods assuming tissue homogeneity. Chapter 2 introduces simulated annealing as a robust method of exploring the limits of a two-layer pure diffusion model in determining the optical properties of a two-layer turbid medium. The inadequacies of pure diffusive transport lead to inaccurate optical property estimates for the top layer. To improve on these estimates a hybrid Monte Carlo (MC)--diffusion model for FD photon transport was developed and presented in Chapter 3. The hybrid model was shown to accurately model MC simulated reflectance data for all optical properties in the physiological range. In Chapter 4 an efficient hybrid simplex--simulated annealing global optimization algorithm was introduced to demonstrate that the hybrid transport model can, in principle, accurately determine all optical properties of a two-layer turbid medium. The practical feasibility of the method was tested with high accuracy FD experimental measurements. Some preliminary results and future directions towards the in vivo implementation of the method are discussed.</p> / Doctor of Philosophy (PhD)

<p>In this thesis, a method that extracts the time course of radioactivity concentration in the blood from brain PET images is developed as a non-invasive alternative to arterial blood sampling. Even though the methodology is developed for 6-[18 F]fluoro-L-m -tyrosine (Fm T), a presynaptic dopaminergic radiotracer, it is generalisable to other radiotracers. The method is based on predefined regions of interest (ROI) drawn on the largest cerebral blood vessels, the venous sinuses, which are visible in the PET images. The time course of radioactivity in the cerebral blood was initially corrected for partial volume and spillover using a population value for the calibre of the blood vessel. The method was refined by parametrising the ROIs in order to extract the calibre of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. In a validation study, the radioactivity concentration was recovered to 100 ± 4% in syringes filled with an 11 C solution and inserted into a water-filled cylindrical phantom. Even though the diameter of syringes was estimated with an accuracy of half a pixel (1mm) in the phantom studies, the method systematically overestimated the blood vessel calibre by 2-3mm compared with measurements made in magnetic resonance venograms in human studies. The application of the parametric ROIs method to clinical studies awaits the development of more accurate scatter correction methods and the implementation of correction for head motion. The between-subject variations in the blood vessel calibre were measured to be comparable to the bias given by the parametric ROIs, thereby justifying the use of a population value over current subject-specific values. A compartmental model relating the radiotracer Fm T, its main radiolabelled metabolite and their exchange between plasma and erythrocytes was also developed in order to transform the time course of total radioactivity measured in whole blood into the time course of the unmetabolised radiotracer in plasma. Presynaptic dopamine function is severely disturbed in Parkinson's disease (PD) with a pattern of striatal involvement (posterior putamen dopamine levels decreased compared to that in caudate nucleus on the side opposite to the clinically impaired limbs) that distinguishes it from other movement disorders. Compared to arterial blood sampling, the image-derived plasma input function enabled the discrimination of normal and PD subjects as well as the identification of the affected and unaffected sides of the PD subject. The image-derived plasma input function also classified 20 of the 21 consecutive patients suspected of suffering from a variety of movement disorders into the same categories as determined using an indirect cerebellar input function. Using image-derived input functions, quantitative analyses of PET/Fm T studies are feasible in a clinical setting and, in combination with striatal patterns of Fm T uptake, the method provides useful diagnostic information in individual patients. (Abstract shortened by UMI.)</p> / Doctor of Philosophy (PhD)

<p>The phenomenon of cortical plasticity is important for understanding brain functions and treating neural diseases. Recent studies have suggested that neural plasticity contributes to cortical reorganization after accidental amputation of a limb and to recovery of function in stroke victims. Cortical plasticity has also been implicated in musical skills and an enhanced sense of hearing in blind humans. The experiments of this thesis utilize Magnetoencephalography (MEG) and Electroencephalography (EEG) to investigate remodeling of the human auditory cortex by musical training. Characteristics of the transient late auditory evoked potentials (AEPs) and magnetic fields (AEFs) are contrasted between musicians and nonmusicians. The principal goal of the thesis is to establish whether musicians and non-musicians respond differently to stimuli of musical timbre, and to begin to understand how these differences occur. The effect of stimuli properties on AEPs and AEFs and the distinct qualities of the two functional imaging methods are also investigated. Three experiments are reported each showing that P2 responses evoked by musical tones and by pure tones matched in fundamental frequency to the musical tones are larger in musicians than in nonmusicians. Enhancement of the P2 appeared in electrical as well as in magnetic recordings. Evidence for enhancement of P1, N1, and N1c auditory evoked potentials in musicians was also observed, but not under all conditions that were studied. P2, N1, and N1c responses appeared to be influenced by spectral properties of the acoustic stimuli in different ways. The mechanisms underlying these findings are discussed.</p> / Doctor of Philosophy (PhD)

<p>This thesis deals with advancements made in the field of Electron Paramagnetic Resonance (EPR) for biophysical dosimetry with tooth enamel for accident, emergency and retrospective radiation dose reconstruction. A methodology has been developed to measure retrospective radiation exposures in human tooth enamel. This entails novel sample preparation procedures with minimum mechanical treatment to reduce the preparation induced uncertainties, establish optimum measurement conditions inside the EPR cavity, post process the measured spectrum with functional simulation of dosimetric and other interfering signals, and reconstruct dose. By using this technique, retrospective gamma radiation exposures as low as 80 ± 30 mGy have been successfully deciphered. The notion of dose modifier was introduced in EPR biodosimetry for low dose measurements. It has been demonstrated that by using the modified zero added dose (MZAD) technique for low radiation exposures, doses in the 100 mGy range can be easily reconstructed in teeth which were previously thought useless for EPR dosimetry. Also the use of a dose modifier makes robust dose reconstruction possible for higher radiation exposures. The EPR dosimetry technique was also developed for tooth samples extracted from rodents, which represent small tooth sizing. EPR doses in the molars, extracted from mice irradiated with whole body exposures, were reassessed and shown to be correct within the experimental uncertainty. The sensitivity of human tooth enamel for neutron irradiation, obtained from the 3 MV McMaster K. N. Van de Graaff accelerator, was also studied. For the first time this work has shown that the neutron sensitivity of the tooth enamel is approximately 1/10th of the equivalent gamma sensitivity. Parametric studies for neutron dose rate and neutron energy within the available range of the accelerator, showed no impact on the sensitivity of the tooth enamel. Therefore, tooth enamel can be used as a dosimeter for both neutrons as well as gamma radiation. We will continue experiments to develop this endpoint as a sensitive accident or emergency tool for our response capabilities.</p> / Doctor of Philosophy (PhD)

The neutron irradiation facility developed at the McMaster University 3 MV Van de Graaff accelerator will be employed to assess in vivo elemental content of aluminum and manganese in human hands. These measurements will be carried out to monitor the long-term exposure of these potentially toxic trace elements through hand bone levels. This thesis addresses two important issues regarding in-vivo neutron activation (IVNAA) of the hand; the first relates to the optimization of operating conditions at the McMaster University 3 MV KN Van de Graaff accelerator to produce neutrons via the ⁷Li(p, n)⁷Be reaction for in-vivo neutron activation analysis and the second relates to the evaluation of the total dose equivalent delivered to the patient hand undergoing irradiation using a 1/2" diameter tissue equivalent proportional counter (TEPC). The operating conditions at the 3 MV KN Van de Graaff accelerator have been optimized by employing a long counter designed for this study to monitor the neutron fluence and a NaI(TI) detector to measure the ⁷Be activity produced as a result of (p, n) interactions with ⁷Li. It was observed that inefficient target cooling and the presence of oxide layers on the target surface resulted in lower measured yields than those calculated. The computational method described in this work to estimate the average radiation dose equivalent delivered to a patient's hand during irradiation employs the neutron and gamma doses measured using a 1/2" diameter TEPC and the quality factor of the neutron beam calculated by using the Monte Carlo radiation transport code, MCNP4B. Based on the the estimated doses delivered to a patient's hand, the proposed irradiation procedure for the IVNAA measurement of manganese in human hands (Med Phys 29(11) (2002) 2718) with normal (1ppm) and elevated manganese content can be carried out with a reasonably low dose of 31 mSv to the hand which is less than the recommended maximum permissible dose equivalent limit (50 mSv) for such diagnostic procedures. 63% of the total dose equivalent is delivered by the non-useful fast neutron group (>10 keV); the filtration of this neutron group from the beam will further reduce the dose equivalent to the patient's hand. / Doctor of Philosophy (PhD)

The goal of this research is to evaluate the secondary prompt gamma (PG) yield from proton therapy at high characteristic energies from MC model simulations and experimental data. Recent studies indicate that target composition influences PG characteristic energy and yield, and the quantification of PG may be used to offer real-time dose verification for proton therapy. In this study PG analysis was performed for MC simulations to evaluate the characteristic measurements and total yield of secondary PG emitted from a target in the 0-8 MeV range from a proton therapy beam over a range of four different beam energies (70 MeV, 160 MeV, 200 MeV, 220 MeV). This was repeated in several target materials (carbon, calcium oxide, calcium fluoride, PMMA, and HDPE) in order to evaluate the influence of the incident energy and the target material on the PG yield and energy spectra. PG energy spectra determined from the specified target materials indicated that the 3.74 MeV energy peak shows a linear correlation between PG intensity and calcium mass fraction of the target material. 6.13 MeV and 4.44 MeV energy peak are not unique to the respective, oxygen and combined oxygen and carbon, mass fraction of the target material. This relationship is complicated by the addition of calcium within the target. Experimental data was collected in order to validate the computational model based on comparison of relative characteristic energy peek intensities. The relative peak ratio determined from experimental data is in good agreement with model prediction, the combined peak ratio is within 0.2%.

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The accurate automated extraction of arterial and venous (AV) trees in fundus images subserves investigation into the correlation of global features of the retinal vasculature with retinal abnormalities. The accurate extraction of AV trees also provides the opportunity to analyse the physiology and hemodynamic of blood flow in retinal vessel trees. A number of common diseases, including Diabetic Retinopathy, Cardiovascular and Cerebrovascular diseases, directly affect the morphology of the retinal vasculature. Early detection of these pathologies may prevent vision loss and reduce the risk of other life-threatening diseases. Automated extraction of AV trees requires complete segmentation and accurate classification of retinal vessels. Unfortunately, the available segmentation techniques are susceptible to a number of complications including vessel contrast, fuzzy edges, variable image quality, media opacities, and vessel overlaps. Due to these sources of errors, the available segmentation techniques produce partially segmented vascular networks. Thus, extracting AV trees by accurately connecting and classifying the disconnected segments is extremely complex. This thesis provides a novel graph-based technique for accurate extraction of AV trees from a network of disconnected and unclassified vessel segments in fundus viii images. The proposed technique performs three major tasks: junction identification, local configuration, and global configuration. A probabilistic approach is adopted that rigorously identifies junctions by examining the mutual associations of segment ends. These associations are determined by dynamically specifying regions at both ends of all segments. A supervised Naïve Bayes inference model is developed that estimates the probability of each possible configuration at a junction. The system enumerates all possible configurations and estimates posterior probability of each configuration. The likelihood function estimates the conditional probability of the configuration using the statistical parameters of distribution of colour and geometrical features of joints. The parameters of feature distributions and priors of configuration are obtained through supervised learning phases. A second Naïve Bayes classifier estimates class probabilities of each vessel segment utilizing colour and spatial properties of segments. The global configuration works by translating the segment network into an STgraph (a specialized form of dependency graph) representing the segments and their possible connective associations. The unary and pairwise potentials for ST-graph are estimated using the class and configuration probabilities obtained earlier. This translates the classification and configuration problems into a general binary labelling graph problem. The ST-graph is interpreted as a flow network for energy minimization a minimum ST-graph cut is obtained using the Ford-Fulkerson algorithm, from which the estimated AV trees are extracted. The performance is evaluated by implementing the system on test images of DRIVE dataset and comparing the obtained results with the ground truth data. The ground truth data is obtained by establishing a new dataset for DRIVE images with manually classified vessels. The system outperformed benchmark methods and produced excellent results.