Magnetic Resonance (MR) imaging is a 3-D, multi-slice, radiological technique that acquires multiple intensities corresponding to each voxel. The transverse relaxation time, T$\sb1$, and the axial relaxation time, T$\sb2$, are two commonly obtained intensities that tend to be orthogonal. Automated segmentation of 3-D regions is very difficult because some borders may be delineated only in T$\sb1$ images, while others are delineated only in T$\sb2$ images. Classical segmentation techniques based on either global histogram segmentation or local edge detection often fail due to the non-unique and random nature of MR intensities. A 3-D, neighborhood based, segmentation method was developed based on both spatial and intensity criteria. The spatial criterion requires that only voxels connected by an edge or face to a voxel known to be in the region be considered for inclusion. Therefore, the region "grows" outward from an initial voxel. An intensity criterion that tries to balance local and global properties must also be satisfied. It determines the vector distance between the intensity of the voxel in question and a characteristic intensity for the neighboring voxels known to be in the region. Voxel intensities within a 95% confidence interval of the characteristic intensity are considered part of the region. The kernel size used to determine the characteristic intensity determines the balance between global and local properties. The segmentation terminates when no additional voxels satisfy both spatial and error criteria. Some regions, such as the brain compartments, are highly convoluted, resulting in a large number of border voxels containing a mixture of adjoining tissues. A sub-voxel estimate of the fractional composition is necessary for accurate quantification. A least-squares estimator was derived for the fractional composition of each voxel. Additionally, a maximum likelihood estimator was derived to globally estimate the fraction for all mixture voxels. This estimator is a minimum variance estimator in contrast to the least-squares estimator. The estimation methods in conjunction with the 3-D, neighborhood based, segmentation method resulted in an automated, highly accurate, quantification technique shown to be successful even for the brain compartments. Widespread applicability of these methods was further demonstrated by segmentation of kidneys in CT images.

The use of contrast media in positron emission tomography (PET)/computed tomography (CT) dual modality imaging has been shown to cause artifacts in the PET image. These artifacts are attributed to an overestimation of the PET attenuation coefficients, which are obtained from contrast-enhanced CT numbers. This dissertation evaluates three algorithms, which segment intravenous contrast-enhanced tissue from CT images, so as to minimize this bias. The algorithms evaluated are the template matching; 3D region growing, and snake-based methods, and they were tested using 5 patient studies. Segmentation results for each method were compared to corresponding manually segmented images on a pixel-wise basis. The snake-based technique was judged to be most suitable for efficiently segmenting the contrast-enhanced CT images. This technique can lead to a more efficient acquisition of high quality PET/CT data, by enabling the use of contrast media without introducing related artifacts.

The distribution of neuropeptide Y (NPY) receptor sites was investigated in certain mammalian species using receptor autoradiography and membrane binding assay techniques. NPY receptor sites are discretely distributed throughout the central nervous systems of hamster, rat, guinea pig and monkey but are particularly concentrated in cortex and hippocampus. NPY receptor autoradiography techniques also revealed important labelling of numerous thalamic nuclei while most hypothalamic nuclei showed surprisingly low densities of NPY receptor sites, considering the high levels of NPY-like immunoreactivity in this brain area. The widespread distribution of NPY receptor sites suggests that this peptidergic system must have important roles in mammalian central nervous system. In particular, the possible involvement of NPY in cognitive function deserves further investigation since we observed that ($ sp3$H) NPY receptor site densities are decreased in temporal cortex and hippocampus of individuals decreased with Alzheimer's disease. / The possible existence of NPY/peptide YY (PYY) receptor subtypes was investigated in the rat brain. Overall, the similar autoradiographic distribution of ($ sp{125}$I) BH-NPY and ($ sp{125}$I) PYY in most areas suggests that these two receptor probes most likely interact with the same population of NPY/PYY receptor sites. ($ sp{125}$I) PYY may recognize both a high and low affinity state/subtype of NPY/PYY receptors while ($ sp{125}$I) BH-NPY recognize a single affinity state of receptor having the binding characteristics of the low affinity ($ sp{125}$I) PYY receptor state/subtype. The exact nature of this high affinity receptor state/subtype remains to be established. / Finally, the structural requirements of NPY receptors in central (CNS) and peripheral (PNS) nervous systems were also examined with a binding assay on rat brain membrane preparation and with the rat vas deferens bioassay preparation. The amino acid residues responsible for the activation of NPY receptors in the rat vas deferens preparation lie in the C-terminal half of the NPY molecule as revealed by the loss of potency, but not of biological activity with C-terminal fragments up to NPY$ sb{18-36}$. The N-terminal portion of the NPY molecule appears to be mostly important to insure adequate affinity for central and peripheral NPY receptors. Moreover, a series of NPY analogs revealed that the two tyrosine residues in position 20 and 21 are not directly involved in NPY receptor activation in this bioassay preparation, although they appear relatively important for the maintenance of adequate affinity for the receptors. Interestingly, modifications of the tyrosine residue in position 20 led to the development of two analogs demonstrating a certain degree of selectivity for the PNS receptors while other modifications of tyrosine residues in position 21 may provide some selectivity for CNS receptor sites. (Abstract shortened by UMI.)

Using Monte Carlo techniques, the 18 MV accelerators CL2300 and CL21EX, 8 physical wedges and the enhanced dynamic wedge have been modeled and validated. The simulated PDDs, profiles, output factors and wedge factors are in good agreement with measured values. These models have been applied in the dose calculation of lung cancer patients to investigate the effect of tissue heterogeneity by comparing with the CADplan treatment planning system with and without heterogeneity correction. Plan I and plan II for 8 patients have been re-calculated with the Monte Carlo method. On average, the mean PTV dose calculated with the Monte Carlo method is 2.4% higher than that calculated with CADplan without correction but 2.5% lower than that with EqTAR correction. The Monte Carlo method predicts 13% higher mean lung dose than CADplan without heterogeneity correction. Because of this difference, the risk of radiation pneumonitis based on available NTCP models will be underestimated. A relationship of mean lung dose between two types of dose algorithms can be used to correct this underestimation.

This study involves the measurement of the neutron equivalent dose ( NED) and the induced activity produced from medical linear accelerators. For the NED, various parameters such as the profile, field effects and energy responses were studied. The NED in a Solid Water(TM) phantom was measured and a new quantity, the neutron equivalent dose tissue-air ratio (NTAR), was defined and determined. Neutron production for electron beams was also measured. For the induced activity, comparisons were carried out between different linacs, fields and dose rates. The half life and activation saturation were also studied. A mathematical model of induced activity was developed to explain the experimental results. Room surveys of NED and induced activity were performed in and around a high energy linear accelerator room. Unwanted doses from photoneutrons and induced activity to the high energy linear accelerator radiotherapy staff and patient were estimated.

A Cisplatin-resistant subline of a Human Ovarian cancer cell line, A2780 CP also exhibits cross resistance to 60Co gamma-radiation. Cellular Glutathione (GSH) levels were measured by the Tietze Spectrophotometric method. GSH levels in A2780 CP cells were approximately three time that of the parental A2780 cells. In cells depleted of GSH by L-Buthionine Sulfoximine (BSO), Cisplatin-resistance was significantly decreased in both cell lines. BSO had no effect on the radiation resistance of either cell lines. However treatment of cells with a combination of BSO and Dimethyl Fumarate (DMF) significantly decreased the radio-resistance in A2780 CP cells. The combination treatment had no effect on the radio-response of the parental cells. Ethacrynic acid (EA), an inhibitor of Glutathione S-Transferase (GST) activity had no effect on cellular GSH levels nor did it affect the Cisplatin or radiation resistance in either cell line. These results suggest that GSH levels are involved in Cisplatin and radiation resistance in these cells. However the mechanism of GSH involvement in radiation and Cisplatin-resistance appears to be different in the cell lines studied.

The goals of the research work presented in this thesis were (i) to determine the accuracy of lateralization of temporal lobe epilepsy (TLE) by proton magnetic resonance spectroscopic imaging (MRSI) and magnetic resonance imaging (MRI) based volumetric measurements (MRIVol) in comparison with the current "gold standard" of clinical-EEG lateralization, (ii) to optimize the sensitivity of the MRSI and MRI methods (iii) to examine the surgical outcome in groups of patients undergoing surgical treatment, and (iv) to provide insights into the pathogenesis of partial epilepsies. / Early on we confirmed the usefulness of measuring hippocampal formation (HF) volumes in the lateralization of TLE, and showed, for the first time, that the additional determination of amygdala (AM) volumes improves lateralization (paper 1). These findings were specific for temporal lobe epilepsy (TLE), as patients with extra-temporal partial seizures did not have atrophy of the AM or HF (paper 1). In several subsequent original studies we focused on the pathophysiology and clinical manifestations of TLE, including the relationship of mesial temporal atrophy (MTA) to seizure frequency and duration (paper 6); the association of MTA with early childhood prolonged febrile convulsions (paper 7); the relation of MTA to scalp (papers 4 and 5) and intracranial EEG findings (paper 3); the relationship between atrophy of the amygdala and ictal fear in TLE (paper 9); the frequency and characteristics of dual pathology (paper 8); the correlation of MTA with surgical outcome (paper 10) and the question of qualitative vs. quantitative assessment of MTA (paper 2). / The work on MRSI included the development of a new protocol for assessment of neuronal metabolic abnormality in vivo in TLE based on the N-acetylaspartate (NAA) resonance measured in anatomically defined regions of the temporal lobes (paper 11). Subsequently, we were the first to show the advantages of combining proton MRSI and MRIVol for lateralization of TLE (paper 12). We also demonstrated that MRSI could be used to discriminate between different types of nonconvulsive seizures (paper 15) and to monitor the progression of chronic encephalitis and focal seizures (Rasmussen's syndrome) (paper 14). More recently we began developing new protocols for the use of MRSI in the lateralization and localization of non-lesional extra-temporal epilepsies (paper 13). (Abstract shortened by UMI.)

This thesis studies various aspects of the accuracy issue in image-guided neurosurgery (IGNS). Factors such as registration, MR geometrical distortions and accuracy of digitizing device, are theoretically described in a general model of IGNS. / The means of registering the patient to its image data is then studied, starting with the definition of registration error. Computer simulations of registration by homologous point matching are described along with a clinical study comparing homologous point matching and surface matching registration methods. / A 3-D MR geometrical distortion experiment performed on a stereotactic frame is presented. These measurements demonstrate the discrepancy that can be observed in the geometry of the frame when imaged with differing read-out gradient directions, and quantitatively evaluate the geometrical distortion associated with the image of the frame of known geometry. / Since geometrical distortion of MR images can adversely affect the accuracy of IGNS, the three-point-Dixon MR pulse sequence is evaluated as a means of estimating the magnetic field inhomogeneity, and hence potential geometrical errors in images. / Finally, an experimental comparison of mechanical and optical localizing devices is described, resulting in a quantitative estimate of the precision and accuracy of both systems.

Electron arc therapy is the treatment of choice for tumours involving large curved surfaces. At the Montreal General Hospital a unique approach to the electron arc therapy was developed in 1986 and has been used clinically ever since. The approach is based on the concept of the characteristic angle beta. / We measured radial percentage depth doses in a polystyrene cylindrical phantom irradiated with electron arc beams having angles beta in the range from 5$ sp circ$ to 100$ sp circ,$ for 9 MeV, 12 MeV, 15 MeV, and 18 MeV electron beam energies. We showed that the characteristic angle-$ beta$ concept can be extended to the beams with nominal energy of 18 MeV. The validity of the empirical relationship, relating the doses in two beams with different energies, was confirmed. A linear relationship between the angle $ beta$ and the depth of dose maximum, the depth of the 85% depth dose, and the depth of the 50% depth dose, was established. The surface dose dependence on the angle $ beta$ was also determined and the bremsstrahlung contamination in the electron arc therapy studied.

An algorithm for optimization of numerous modulated beam weights has been developed. This algorithm employs a penalty function theorem and a simulated annealing (SA) routine to model a large-scale constrained optimization problem incorporating dose and dose volume constraints in reflecting the goal of inverse treatment planning by sparing sufficient healthy tissues while delivering a necessary tumorcidal dose. The convergence property of the dose-volume SA algorithm is investigated for validation. Its performance is also evaluated by comparing the algorithm with a gradient technique minimizing the same dose-volume objective function that incorporates the target dose objectives and organ dose-volume constraints by the penalty functions. The comparison shows that the objective function exhibits a global valley in which multiple local minima with similar outcomes in terms of the function values, the dose-volume histograms, and the dose distributions exist. Thus, the gradient algorithm is preferred for this optimization approach due to its fast efficiency.