This dissertation describes both methodological developments in quantitative functional magnetic resonance imaging (fMRI) of cerebral oxygen consumption, and the results of experiments using these techniques to elucidate the mechanisms linking focal changes in blood flow and oxygen metabolism. Technical contributions presented include a novel MRI pulse sequence for simultaneously monitoring cerebral blood flow and tissue oxygenation with high signal-to-noise ratio, as well as an experiment automation system permitting complex multiparametric studies to be carried out efficiently in large numbers of subjects. These tools enabled us to make a number of significant neurophysiological discoveries with important implications for the design and interpretation of fMRI experiments. In particular, relative changes in cerebral perfusion and oxygen consumption were found to be coupled in a consistent linear ratio of approximately 2:1, respectively, in human visual cortex. A quantitative model predicting that oxygenation-sensitive MRI signals must be extremely sensitive to departures from this coupling ratio was also introduced, revealing that combined perfusion/oxygenation measurement during graded activation is a powerful tool for studying regulatory relationships between these parameters. Predictions based on this model were in excellent agreement with experimental results, supporting model-derived estimates of oxygen consumption and suggesting that the ∼2:1 coupling discovered in visual cortex is likely to apply in most cortical systems. Finally, important non-linear characteristics of fMRI signal dynamics in human visual cortex were revealed, challenging current models of fMRI transient response.

The treatment head of the Clinac-18 medical linear accelerator was modelled using-the EGS4 Monte Carlo simulation package. Photon-energy spectra for fields ranging from 2 x 2 cm$ sp2$ to 20 x 20 cm$ sp2$ in size were generated and the primary and scatter spectra were analyzed separately. The generated x-ray spectra were used in the calculation of the percent depth dose (PDD) distributions for flattened and unflattened 10 MV x-ray beams in a water phantom at a source-surface distance of 100 cm for the various field sizes. The agreement between calculated and measured depth doses is excellent. / Measurements of the dose in the build-up region show that the depth of dose maximum (d$ sb{max}$) increases with increasing field size for fields up to 5 x 5 cm$ sp2$ for both the flattened and unflattened beams. As the field size is increased beyond 5 x 5 cm$ sp2,$ d$ sb{max}$ decreases with increasing field size for the flattened x-ray beam while remaining nearly constant for the unflattened beam. Additionally, the surface dose of the flattened beam is found to approach that of the unflattened beam for large field sizes. Calculations show that the decrease in d$ sb{max}$ as the field size is increased above 5 x 5 cm$ sp2,$ and the rapid increase in the surface dose for the flattened x-ray beam with increasing field size, are due to the degradation of the flattened-beam parameters caused by low-energy photons produced in the flattening filter.

Attenuation and scatter are limiting factors in image quality and quantitation of organ function by single photon emission computed tomography (SPECT). To correct brain images for attenuation an effective water/tissue attenuation coefficient of 0.12 cm$ sp{-1}$ (at 140 keV) or larger has been recommended in order to compensate for the additional bone (skull) attenuation. / It has been determined that the reconstructed images are overcorrected in the centre by 5%, and the optimum correction occurs for a reduced coefficient of 0.09 cm$ sp{-1}$. The overcorrection is due to increased attenuation at the edges of all projections where the path length through the bone is greater, although the bone also increases the scatter at the projection edges. / A correction scheme which uses effective bone and water coefficients was developed to compensate for the attenuation. Alternatively, prior to attenuation correction, a common scatter correction was found to be effective in explicitly removing the bone and water scatter.

In this thesis, the use of the Fricke-gelatin dosimeter in NMR-based radiation dosimetry is investigated. The relationship between the proton spin-lattice relaxation rate and the absorbed dose for the Fricke-gelatin dosimeter is determined using pulsed NMR at 25 MHz. This relationship is used to calculate the NMR dose sensitivity. Practical considerations of Fricke-gelatin dosimetry, such as the spontaneous conversion of ferrous to ferric ions and the effects of oxygen and sodium chloride on the dose response, are determined. Sensitization of the dosimeter by bubbling with a nitrous oxide/oxygen gas mixture is investigated. The system is modelled assuming a multi-site fast exchange between water bound to gelatin, water bound to ions, and water in the bulk. Preliminary aspects of the model are investigated and compared with experimentally determined data. Finally, the utility of the dosimeter is demonstrated by magnetic resonance imaging a Fricke-gel irradiated with an $ sp{192}$Ir radioactive seed.

Three-dimensional (3D) ultrasound is an emerging new technology with numerous clinical applications like measuring the volume of the prostate, monitoring fetal development, or evaluating brain shift during neurosurgery. Ultrasound probe calibration is an obligatory step in order to build 3D volumes from 2D images acquired in a freehand ultrasound system. The role of calibration is to find the transformation that relates the image plane to a sensor attached on the probe. This thesis is a comprehensive review of what has been published in the field of ultrasound probe calibration for 3D ultrasound. The thesis covers the topics of tracking technologies, ultrasound image acquisition, phantom design, speed of sound issues, feature extraction, least-squares minimization, temporal calibration, calibration evaluation techniques and phantom comparisons. The calibration phantoms and methods have also been classified in tables to give a better overview of the existing methods.

Three-dimensional modeling has become an important tool for non-destructive evaluation of tissue for experimental and clinical uses. However, its range of applications is limited by its dependence on expensive imaging modalities. The current research explores ordinary radiographs as an alternative for three-dimensional modeling in several applications relating to vertebral fracture detection and treatment. An algebraic reconstruction algorithm was developed to replace CT in the construction of patient-specific vertebral finite element models for the evaluation of fracture risk in elderly individuals. CT-based models have shown far stronger specificity in detecting at-risk osteoporotic vertebrae than DEXA, but have not been adopted into the clinic because of equipment cost, limited reimbursement codes, radiation exposure, and expertise requirements. Our radiograph-based technique was able to replicate biomechanical predictions made from CT scans to within 7% error, providing an improved alternative to DEXA with less interaction required from the operator than traditional modeling. A similar algebraic technique was employed to investigate the internal changes in a vertebral body during compression to fracture. Because testing apparatus are not compatible with traditional 3-D imaging modalities, we evaluated regional changes in apparent density and deformation of the vertebral shell using periodic sets of 4 radiographs. Damage was observable in an internal area of high strain energy density, then propagated across the inferior endplate causing whole bone failure. Vertebroplasty is the most effective treatment of vertebral compression fractures. It is performed with a minimum of planning and evaluation primarily to avoid cement leakage. However, optimization is required to reduce the incidence of post-treatment adjacent vertebral fractures have. We have thus developed a method of reconstructing the bolus shape within the bone based on a series of images acquired with fluoroscopic radiography. The cement volume was calculated with a mean error of 8%, and the location and shape of the bolus were visualized in both two and three dimensions. Three-dimensional imaging modalities allow better visualization and diagnostics and can lead to more precise modeling and optimization of surgical procedures. The techniques presented in this thesis aim to make imaging more accessible and broaden the associated range of applications.

The metallofullerenes, Hox C82 (x = 1,2) and Gd C 82 were generated, sublimed from carbon-arc soot, and further purified by HPLC. Sample purity was then judged by LD-TOF MS and compared with purities obtained by ICP-AE and NAA (Ho only) metal assays. Results indicated that the mass spectrometry data overestimated the purity of the metallofullerene samples by about a factor of two. The water-soluble metallofullerol derivatives, Hox C82(OH)y and Gd C82(OH) y were then prepared, and studies were conducted to determine their proton relaxivities in aqueous solution and magnetic properties in the solid state. The relaxivity of Gd C82(OH)y (R1 = 19.9 mM-1 sec.-1 at 20 MHz, 40°C) in aqueous solution was 5 times greater than commercially available MRI contrast agents, indicating that Gd C82(OH)y (6.4 muB at 100K) holds great promise as an MRI contrast agent. In comparison, Hox C82(OH)y did not enhance proton relaxation and had a magnetic moment lower than its Hox C82 precursor (Hox C82(OH)y = 3.8--5.2 muB at 300K, vs. Hox C82 = 5.5--7.8 mu B at 300K). Finally, full biodistribution studies of a water-soluble radioactive metallofullerene compound were conducted using 166Ho x C82(OH)y in BALB/c mice. For this work, the metallofullerol was neutron-activated (165Ho (n,gamma) → 166Ho) to prepare the 166Hox C82(OH) y radiotracer [Egamma(166Ho) = 80.5 keV] and was monitored after intravenous administration for up to 48 hours by dissection radioanalysis for comparison with a Na2[166Ho(DTPA)(H2O)] control study. Results showed 166Ho localization in the liver with slow clearance, as well as slow uptake by bone without clearance. In contrast, excretion of the control compound was nearly quantitative after 1 hour. The fate of 166Ho was also explored by a metabolism study of 166Hox C82(OH)y in Fischer rats. Results demonstrated 20% clearance of the 166Ho within 5 days. Together, these studies comprise a demonstration of metallofullerene materials utility in radiotherapy, radiodiagnostics, and MRI contrast agent applications.

This thesis establishes normal age-related changes in the magnetic resonance (MR) T1 and T2 relaxation time constants using data collected as part of the National Institutes of Health (NIH) MRI Study of Normal Brain Development. This ongoing multi-centre study of normal brain and behaviour development provides both longitudinal and cross-sectional data and has enabled us to investigate the relaxation time constant evolution in several brain regions for children within the range of 0-4.5 years. Due to the multi-centre nature of the study and the extended period of data collection, periodically scanned inanimate and human phantoms were used to assess intra and inter-site variability. The main finding of this thesis is the parametrization of the mono-exponential behaviour of both the T1 and T2 relaxation time constants from birth until 4.5 years of age. This behaviour is believed to reflect the rapid changes in water content as well as myelination processes observable during neonatal brain development. These results, comprising over 200 subject scans, represents a subset of a publicly available normative pediatric MRI database, providing a basis for comparison for studies assessing normal brain development and deviation due to various neurological disorders.

This thesis presents two techniques for enhancing the volume coverage and temporal resolution of functional magnetic resonance brain imaging on conventional clinical scanners, namely, echo-shifting and retrospective temporal resolution selection (RTRS). The techniques are compared with conventional 2D gradient echo imaging on the bases of speed and sensitivity to functional changes, and the necessary theory is reviewed to develop physical models explaining the different properties observed. / Acquisition, reconstruction, and analysis software packages for functional brain mapping are presented and demonstrated with visual stimulation. The echo-shifted sequence permitted acquisition of 3D maps of brain activity which could be better correlated with local anatomy than 2D maps, and the RTRS method provided physiological response curves with greatly increased temporal resolution.

A computer program was developed during the course of this work to calculate electron arc dose distributions with the angle $ beta$ concept. The angle $ beta$ uniquely describes the dependence of radial percentage depth doses an electron arc therapy on the nominal field width, isocenter depth, and virtual source-axis distance. The $ beta$ concept can be used in clinical situations to determine the field width when the isocenter depth and the required radial percentage depth dose are known. This thesis presents an overview of the physical properties of electron arc therapy and describes in detail the angle $ beta$ pseudo-arc technique used at McGill. A description of the algorithms used in the computer program is given the $ beta$ technique is compared to measurements and other calculation methods.