To optimize delivery of radiation therapy treatments, accurate knowledge of absorbed dose in the clinical beam is essential. In this work we investigated issues related to the use of different types of ionization chambers for accurate radiation dosimetry. We determined values of Pwall at 60Co for plane-parallel chambers and used them to derive the conversion factors kecal k'R 50 or kQ for a 20 MeV electron beam. Our results agreed within 0.4% with kQ values given in the IAEA TRS-398 protocol, but differences of up to 1.8% were found between our kecalk' R50 values and those in the AAPM TG-51 protocol. We also investigated the behavior of two liquid-filled ionization chambers in megavoltage photon beams, examining stability, ion recombination and beam quality dependence. Methods for determining and correcting for recombination were investigated. Preliminary results show that the energy dependence of a liquid-filled chamber can typically be limited to less than 1% for megavoltage photon beams.

The availability of accurately aligned, whole body, functional PET images has a significant impact on the diagnosis of malignant disease and on identifying and localizing metastasis. Gamma ray attenuation correction is essential in all quantitative PET studies. / The object of this study was to explore the possibility of using beta-gamma coincidence as an attenuation correction technique in order to improve transmission scan image quality. / This study consisted of testing and implementing a beta-gamma attenuation correction technique on an animal PET scanner. In its final form the system uses 68Ge sources enclosed in plastic scintillator cylinders coupled to PMTs. The detection of positrons is activated by the energy loss in the scintillator medium. This system is used in coincidence with one of the animal PET scanner's BGO crystal detectors in order to acquire transmission scans.

Proton Magnetic Resonance Spectroscopy (MRS) is an effective technology for imaging axonal damage in the brains of multiple sclerosis (MS) patients. This is based on decreases in signals from N-acetyl groups, which come primarily from the neuronal marker, N-acetylaspartate (NAA). Magnetic Resonance Spectroscopic Imaging (MRSI) visualizes the spatial distribution of the NAA intensities in the brains of MS patients. It can be combined with conventional Magnetic Resonance Imaging (MRI) and other clinical information in order to better understand the disease pathology. / This thesis comprises three independent but interconnected manuscripts concerning the application of MRSI and MRI to clinical researches in MS. (1) In the first, a statistical analysis strategy for multimodal analysis of MR spectroscopic images was developed. This method allowed for quantification of differences in images of different subgroups of MS patients and the relationship between chemical pathology, clinical disability, duration of disease, and lesions on T2-weighted MRI. (2) The statistical method was applied to serially collected MRSI data from 28 patients with MS (11 relapsing remitting (RR) and 17 secondary progressive (SP)) and 12 normal controls. Results showed that the NAA intensity was lower in the normal appearing white matter (NAVM) of MS patients than that in normal controls and the NAA intensity was 8.2% lower (p < 0.01) in the NAWM of SP than of RR patients. The decrease in NAA in NAWM over time correlated strongly (p < 0.001) with changes in disability in the RR subgroup. These results highlighted an association between axonal damage or loss and increasing disability in MS and suggested that accumulation of secondary axonal damage in the NAWM might be an important mechanism of functional impairment with this disease. (3) Finally, a computer package integrating spatial statistical methodologies adopted in this project and other image processing methods was developed. This package can also serve as a tool for medical imaging data organization, visualization, and manipulation. It will be used by researchers in the field to analyze functional imaging data.

<p> The goal of this research is to study tissue growth via developing mathematical formulations and computational modeling. Tissue growth modeling has many applications --- including tumor growth, wound healing, bone remodeling, epithelial tissue remodeling, and other problems in developmental biology. Key to this study is incorporating the results of the analysis of non-destructive medical images that augment the models. Quantitative image analysis for the purpose of providing input parameters for and validation of tumor growth models (TGMs) is discussed. Two types of computational TGMs are studied in detail: one is based on the logistic equation, the other is based on the theory of porous media, or mixture theory. For the mixture-based model, we developed an algorithm that couples a level set method to track tumor boundaries while the tissues themselves are treated as a perfused mixture. After the mathematical foundation of each of the TGMs is formulated, we discuss implementation aspects, along with computational results. Finally, we validate the computational results with experimental observations of tumor volume versus time via imaging data acquired from animal models. The RMS deviation between predicted and observed values is as close as 11\% of the time-averaged volume.</p>

<p> We developed a novel large-stroke deformable mirror for focus control and spherical aberration correction. The mirrors fabricated using MEMS technology provide full range (150-200 &micro;m in tissue) of focus scanning at high numerical aperture (N.A.=0.5-0.7) for confocal microscopy and optical coherence tomography (OCT). In addition to large stroke, low power consumption and high speed operation are other key factors of the developed devices. The impact of this project is broad since the miniaturized deformable mirrors have a wide range of applications. In addition to focus scanning in microscopes they can also be used in small form factor systems such as cell phone cameras and robot vision. Furthermore, laser based microscopes equipped with the focus control mirror may be useful for skin cancer diagnosis and treatment. This thesis consists of seven chapters. The first chapter introduces optical focus control and focus control elements. The second chapter describes different schemes for optical focus control in imaging systems including transmissive variable lenses. The principle of operation, fabrication, and characterization of electrostatic deformable mirrors are reviewed in Chapter 3. High-speed focus control mirrors with controlled air damping are discussed in Chapter 4. In this chapter a model adopted from the analysis of MEMS microphone is used to design the backplate of a MEMS deformable mirror. Moreover, electrostatic-pneumatic MEMS deformable mirrors are introduced in Chapter 5. Analytical model is developed for electrostatic-pneumatic actuation in order to design a MEMS mirror with two membranes. Applications of MEMS deformable mirrors are demonstrated in optical systems in Chapter 6. Finally, a summary and future work are discussed in Chapter 7. The fabrication process details are given in Appendix A.</p>

Two ultrasound systems were studied to investigate the effects of positional and volumetric prostate variations on dosimetry over the course of external radiation therapy. A 2D system, currently used at the Montreal General Hospital for patient repositioning, was compared to a 3D system invented recently. Prostate variations were quantified from ultrasound images acquired daily during a 2003 clinical study. A method was devised to introduce ultrasound information in a Monte Carlo Treatment Planning System previously developed at McGill. Patient repositioning was evaluated for both systems using dose-volume histograms of Voxel Monte Carlo dose calculation. Repositioning with the 3D system, neglecting volume changes, was found to bring the target dose to within 1 % of the planned dose, rather than the 12 % of the clinical 2D system. However, when considering the varying 3D volumes, the dose could only be corrected to within 7 %. These results indicate that the 3D system provides not only a more accurate assessment of prostate displacements, but also volumetric information that significantly affects the dosimetry.

We describe the geometric and dosimetric characteristics of a device developed to modify the penumbra of an electron beam and thereby improve the dose uniformity in the overlap region when fields are abutted. The device is a Lipowitz metal block placed on top of the electron applicator's insertion plate and positioned to stop part of the electron beam. The air-scattered electrons beyond the block increase the penumbra width from about 1.4 to 2.7-3.4 cm. The modified penumbra is broad and almost linear at all depths for the 9 MeV and 12 MeV electron beams used in this study. Film dosimetry was used to obtain beam profiles and isodose distributions. Without the penumbra generator, lateral setup errors of 2 to 3 mm may introduce dose variations of up to 20% in the junction region. Similar setup errors cause less than 5% dose variations when the penumbra generator is used to match the fields.

Background. For stage I and II breast cancer, the standard treatment is partial mastectomy followed by radiation treatment. The risk of local recurrence ranges from 6 to 9%. A controversy exists as to whether there is an increased risk of local recurrence as a result of excessive delay between surgery and radiation treatment. A natural experiment associated with a prolonged waiting time in our institution provided an opportunity to evaluate the impact of waiting times for radiation treatment of breast cancer on the risk of local recurrence. / Methods. Between January 1988 and December 1989, 486 patients with stage I or II breast cancer from McGill hospitals were treated with radiotherapy. Their charts were reviewed, and information with regard to prognostic factors, such as age, tumor size, histological grade, number of positive lymph nodes, and margins of resection, was abstracted. The interval between the date of surgery and the date of initial radiation treatment, and events, such as local recurrence, metastases and death, were noted. / Results. At five years, the local recurrence rate was 8%, the metastatic rate 13%, and the disease-free survival rate 89%. In the univariate analysis, the risk of local recurrence was associated with younger age, higher histological grade, and time to radiation treatment. In the multivariate Cox proportional hazard models, higher histological grade and time to radiation treatment were significant. Using recursive partitioning, the risk of local recurrence was almost five times higher for patients who waited in excess of 79 days for radiation treatment. / Conclusion. Delay in radiation treatment is associated with an increased risk of local recurrence of breast cancer.

A new paradigm for the characterization of structure appearance is proposed, based on a combination of grey-level intensity data and a shape descriptor derived from a priori Principal Components Analysis of 3D deformation vector fields. Generated without external intervention, it extends more classical, 2D manual landmark-based shape models. Application of this novel concept leads to a method for the segmentation of medial temporal lobe structures from brain magnetic resonance images. The strategy employed for segmentation is similar to that used in other appearance-based approaches, while the resulting output data is identical to ANIMAL, a non-linear registration and segmentation technique. The proposed method was tested on a data set of 80 normal subjects for which manual and ANIMAL segmentated structures were available. Experimental results demonstrated the robustness and flexibility of this method. Segmentation accuracy, measured by overlap statistics, is marginally lower (<2%) than ANIMAL, while processing time is 6 times faster. Finally, the applicability of this concept towards shape deformation analysis is presented.

The brain can be explored while a subject executes different tasks. Such techniques are commonly referred as activation studies. The regions of the brain involved in a particular task can be located by comparing regional differences in tracer concentration to a control state. Group of neurons in the brain form complex logical circuits and their activities increase while they interpret a stimulation. These neuronal activities require glucose and oxygen and these substances travel in the blood following hemodynamic rules. Many factors influence the hemodynamic response induced by brain activation (FRIBA), but certain aspects of its temporal behavior are still unclear. A special technique was implemented with an ECAT EXACT HR+ (CTI/Siemens) to fulfil this lack in PET activation studies. The new HR+ has this 3D option, which can help to evaluate the FRIBA with a tracer (11C-CO) that remains in the blood vessels to measure the cerebral blood volume (CBV) differences. Only CBV studies can appreciate the temporal course of the FRIBA in PET. The resulting images are, however, very noisy and many pitfalls are present during their analysis. (Abstract shortened by UMI.)