Optical coherence tomography (OCT) is a minimally-invasive imaging modality that generates high resolution cross-sectional images of tissue. The present study employed a 2 mm diameter endoscopic spectral domain OCT system in the in vivo evaluation of the drugs α-Difluoromethylornithine and Sulindac as chemopreventive and chemotherapeutic agents in a mouse model of sporadic colorectal cancer. 30 mm lateral images of each colon at eight different rotations were obtained at five different time points. Visual analysis of the images was performed to determine the number and size of discrete adenomas, with gross photos and histology serving as gold standard confirmation of the final imaging time point. When applied for chemoprevention, DFMO and Sulindac both significantly reduced the incidence of adenoma, appearing to interact additively in the prevention of tumorigenesis. For chemotherapy, however, only Sulindac had a significant effect on the number of adenoma and neither DFMO nor Sulindac significantly affected tumor growth.

Digital breast tomosynthesis (DBT) is a new technology for breast cancer screening that promises to complement mammography or supersede it to become the standard for breast imaging. DBT involves taking multiple images in order to synthesize a new image that represents a slice through the breast volume -- hence the term tomosynthesis. The primary advantage of this paradigm is that it can reduce the amount of overlapping anatomy in the data, leading to improved visualization of potentially-cancerous findings. The difficulty in DBT is quantifying the advantages of the technology and determining the optimal conditions for its clinical use. This dissertation describes a virtual trial framework for assessing and optimizing DBT technology for the specific task of detecting small, low-contrast masses in the breast. It addresses each component of the imaging chain to some degree, from the patients/phantoms to the imaging hardware to the model observers used to measure signal detectability. The main focus, however, is on quantifying tradeoffs between three key parameters that affect image quality: (1) scan angle, (2) number of projections, and (3) exposure. We show that in low-density breast phantoms, detectability generally increases with both scan angle and number of projections in the anatomical-variability-limited (high-exposure) regime. We also investigate how breast density affects the optimal DBT scan parameters. We show task-specific results that support using an adaptive paradigm in DBT, where the imaging system reconfigures itself in response to information about the patient's breast density. The virtual framework described in this dissertation provides a platform for further investigations of image quality in 3D breast imaging.

This dissertation investigates the application of list-mode data to detection, estimation, and image reconstruction problems, with an emphasis on emission tomography in medical imaging. We begin by introducing a theoretical framework for list-mode data and we use it to define two observers that operate on list-mode data. These observers are applied to the problem of detecting a signal~(known in shape and location) buried in a random lumpy background. We then consider maximum-likelihood methods for the estimation of numerical parameters from list-mode data, and we characterize the performance of these estimators via the so-called Fisher information matrix. Reconstruction from PET list-mode data is then considered. In a process we called "double maximum-likelihood" reconstruction, we consider a simple PET imaging system and we use maximum-likelihood methods to first estimate a parameter vector for each pair of gamma-ray photons that is detected by the hardware. The collection of these parameter vectors forms a list, which is then fed to another maximum-likelihood algorithm for volumetric reconstruction over a grid of voxels. Efficient parallel implementation of the algorithms discussed above is then presented. In this work, we take advantage of two low-cost, mass-produced computing platforms that have recently appeared on the market, and we provide some details on implementing our algorithms on these devices. We conclude this dissertation work by elaborating on a possible application of list-mode data to X-ray digital mammography. We argue that today's CMOS detectors and computing platforms have become fast enough to make X-ray digital mammography list-mode data acquisition and processing feasible.

No description available.

No description available.

Osteoporosis is a bone degenerative disease characterized by reduced bone mass, quality and strength, along with changes in microarchitecture and increased incidence of fracture. The significant economic and social costs associated with osteoporotic fractures of the hip and spine have resulted in extensive research efforts directed towards developing an improved understanding of this disease, along with the relationships between osteoporotic bone degradation and fracture risk assessment. The current study investigates the failure behaviour of rat vertebral bodies collected from normal and osteoporotic donors based on the ovariectomized rat model (SHAM and OVX study groups, respectively), along with an additional control group intended to simulate postmenopausal patients with estrogen repletion (OVX+E study group). Simultaneous uniaxial compression testing and X-ray Micro-Computed Tomography (XμCT) were used to visualize and describe the failure behaviour of prepared vertebral body samples during mechanical testing, while providing standard measures of mechanical properties and bone geometry. In tandem with the incremental loading protocol required for simultaneous mechanical testing and XμCT imaging, a continuous loading protocol was also included. Three distinct failure behaviours were observed without bias in the three different study groups and two loading protocols. The primary and secondary failure modes involved fracture initiation in the direct vicinity of vascular apertures present in the dorsal surface of the cortical shell, with failure progression through the sample towards the ventral surface of the cortical shell (primary) or the cranial endplate (secondary). The tertiary failure mode involved localized rupture of the cranial endplate, likely resulting from end-effect related stress-concentrations. Diminished trabecular bone geometry (reduced BV/TV and Tb.N, along with increased Tb.Sp) was accompanied by reduced mechanical properties (reduced ultimate force and ultimate strength) in the OVX study group when compared with the SHAM and OVX+E study groups. Linear regression analyses revealed a shift in the determinants of failure initiation between the SHAM/OVX+E study groups and the OVX study group. In the SHAM and OVX+E study groups, ultimate force was best predicted by indices describing the vascular apertures present in the dorsal cortical shell. In the OVX study group, ultimate force was best predicted by indices describing trabecular bone geometry. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2013-11-21 19:07:38.661

<p>The Application of Magnetic Resonance (MRI) and Computed Tomography Imaging (CT) in the Diagnosis and Management of Maxillofacial Tumours. For decades maxillofacial surgeons over the world have been frustrated by the high and often fatal recurrence of certain advanced jaw tumours. This study conclusively proves that Computed Tomography and especially Magnetic Resonance Imaging significantly decreases recurrence of Odontogenic Keratocyst and Ameloblastoma and allows surgical planning to avoid these recurrences.</p>

Diagnosis of diabetes mellitus, presence of hyperglycemia, and/or insulin resistance confer cardiovascular risk, particularly for diastolic dysfunction. Diabetes is associated with elevated myocardial norepinephrine (NE) content, enhanced sympathetic nervous system (SNS) activity, altered resting heart rate, and depressed heart rate variability. Positron emission tomography (PET) using the NE analogue [11C]meta-hydroxyephedrine ([11C]HED) provides an index of myocardial sympathetic neuronal integrity at the NE reuptake transporter (NET). The hypothesis of this project is that (i) hyperglycemia imparts heightened sympathetic tone and NE release, leading to abnormal sympathetic neuronal function in the hearts of diabetic rats, and (ii) these abnormalities may be reversed or prevented by treatments to normalize glycemia. Sprague Dawley rats were rendered insulin resistant by high fat feeding and diabetic by a single dose of streptozotocin (STZ). Diabetic rats were treated for 8 weeks with insulin, metformin or rosiglitazone, starting from either 1 week (prevention) or 8 weeks (reversal) after STZ administration. Sympathetic neuronal integrity was evaluated longitudinally by [11C]HED PET. Echocardiography measures of systolic and diastolic function were completed at serial timepoints. Plasma NE levels were evaluated serially and expression of NET and β-adrenoceptors were tested at the terminal endpoints. Diabetic rats exhibited a 52-57% reduction of [11C]HED standardized uptake value (SUV) at 8 weeks after STZ, with a parallel 2.5-fold elevation of plasma NE and a 17-20% reduction in cardiac NET expression. These findings were confirmed by ex vivo biodistribution studies. Transmitral pulse wave Doppler echocardiography established an extension of mitral valve deceleration time and elevated early to atrial velocity ratio, suggesting diastolic dysfunction. Subsequent treatment with insulin but not metformin restored glycemia, reduced plasma NE by 50%, normalized NET expression, and recovered [11C]HED SUV towards non-diabetic age-matched control. Diastolic dysfunction in these rats persisted. By contrast, early treatment with insulin, metformin, or rosiglitazone delayed the progression of diastolic dysfunction, but had no effect on elevated NE and reduced [11C]HED SUV in diabetic rats, potentially owing to a latent decrease in blood glucose. In conclusion, diabetes is associated with heightened circulating and tissue NE levels which can be effectively reversed by lowering glycemia with insulin. Noninvasive interrogation of sympathetic neuronal integrity using [11C]HED PET may have added value in the stratification of cardiovascular risk among diabetic patients and in determining the myocardial effects of glycemic therapy.

<p>Optical coherence tomography (OCT) is a non-invasive imaging modality that uses low coherence interferometry to generate three-dimensional datasets of a sample's structure. OCT has found tremendous clinical applications in imaging the retina and has demonstrated great utility in the diagnosis of various retinal diseases. However, such diagnoses rely upon the ability to observe abnormalities in the structure of the retina caused by pathology. By the time an ocular disease has progressed to the point of affecting the morphology of the retina, irreversible vision loss in the eye may already occur. Changes in the functionality of the tissue often precede changes to the structure. Thus, if imaging methods are developed to provide additional functional information about the behavior and response of the retinal tissue and vasculature, earlier treatment for disease may be prescribed, thus preserving vision for the patient. </p><p>Within the last decade, significant technological advances in OCT systems have enabled high-speed and high sensitivity image acquisition using either spectral domain OCT (SDOCT) or swept-source OCT (SSOCT) configurations. Such systems use Fourier processing to extract structural information of a sample from interferometric principles. But such systems also have access to the optical phase information, which allows for functional analysis of sample dynamics. This dissertation details the development and application of methods using both intensity and phase information as a tool for studying interesting biological phenomena. The goal of this work is an extension of techniques to image the vasculature in the retina and enhance the clinical utility of OCT.</p><p>I first outline basic theory necessary for understanding the principles of OCT. I then describe OCT phase imaging in cellular applications as a demonstration of the ability of OCT to provide functional information on biological dynamics. Phase imaging methods suffer from an artifact known as phase wrapping, and I have developed a software technique to overcome this problem in OCT, thus extending its usefulness in providing quantitative information. I characterize the limitations in measuring moving scatterers with Doppler OCT in both SDOCT and SSOCT system. I also show the ability to image the vasculature in the retina using variance imaging with a high-speed retinal imaging system and software based methods to correct for patient motion and create a widefield mosaic in an automated manner. Finally, future directions for this work are discussed.</p> / Dissertation

<p>While it is well known that exposure to radiation can result in cataract formation, questions still remain about the presence of a dose threshold in radiation cataractogenesis. Since the exposure history from diagnostic CT exams is well documented in a patient’s medical record, the population of patients chronically exposed to radiation from head CT exams may be an interesting area to explore for further research in this area. However, there are some challenges in estimating lens dose from head CT exams. An accurate lens dosimetry model would have to account for differences in imaging protocols, differences in head size, and the use of any dose reduction methods.</p><p>The overall objective of this dissertation was to develop a comprehensive method to estimate radiation dose to the lens of the eye for patients receiving CT scans of the head. This research is comprised of a physics component, in which a lens dosimetry model was derived for head CT, and a clinical component, which involved the application of that dosimetry model to patient data. </p><p>The physics component includes experiments related to the physical measurement of the radiation dose to the lens by various types of dosimeters placed within anthropomorphic phantoms. These dosimeters include high-sensitivity MOSFETs, TLDs, and radiochromic film. The six anthropomorphic phantoms used in these experiments range in age from newborn to adult.</p><p>First, the lens dose from five clinically relevant head CT protocols was measured in the anthropomorphic phantoms with MOSFET dosimeters on two state-of-the-art CT scanners. The volume CT dose index (CTDIvol), which is a standard CT output index, was compared to the measured lens doses. Phantom age-specific CTDIvol-to-lens dose conversion factors were derived using linear regression analysis. Since head size can vary among individuals of the same age, a method was derived to estimate the CTDIvol-to-lens dose conversion factor using the effective head diameter. These conversion factors were derived for each scanner individually, but also were derived with the combined data from the two scanners as a means to investigate the feasibility of a scanner-independent method. Using the scanner-independent method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter, most of the fitted lens dose values fell within 10-15% of the measured values from the phantom study, suggesting that this is a fairly accurate method of estimating lens dose from the CTDIvol with knowledge of the patient’s head size.</p><p>Second, the dose reduction potential of organ-based tube current modulation (OB-TCM) and its effect on the CTDIvol-to-lens dose estimation method was investigated. The lens dose was measured with MOSFET dosimeters placed within the same six anthropomorphic phantoms. The phantoms were scanned with the five clinical head CT protocols with OB-TCM enabled on the one scanner model at our institution equipped with this software. The average decrease in lens dose with OB-TCM ranged from 13.5 to 26.0%. Using the size-specific method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter for protocols with OB-TCM, the majority of the fitted lens dose values fell within 15-18% of the measured values from the phantom study.</p><p>Third, the effect of gantry angulation on lens dose was investigated by measuring the lens dose with TLDs placed within the six anthropomorphic phantoms. The 2-dimensional spatial distribution of dose within the areas of the phantoms containing the orbit was measured with radiochromic film. A method was derived to determine the CTDIvol-to-lens dose conversion factor based upon distance from the primary beam scan range to the lens. The average dose to the lens region decreased substantially for almost all the phantoms (ranging from 67 to 92%) when the orbit was exposed to scattered radiation compared to the primary beam. The effectiveness of this method to reduce lens dose is highly dependent upon the shape and size of the head, which influences whether or not the angled scan range coverage can include the entire brain volume and still avoid the orbit.</p><p>The clinical component of this dissertation involved performing retrospective patient studies in the pediatric and adult populations, and reconstructing the lens doses from head CT examinations with the methods derived in the physics component. The cumulative lens doses in the patients selected for the retrospective study ranged from 40 to 1020 mGy in the pediatric group, and 53 to 2900 mGy in the adult group.</p><p>This dissertation represents a comprehensive approach to lens of the eye dosimetry in CT imaging of the head. The collected data and derived formulas can be used in future studies on radiation-induced cataracts from repeated CT imaging of the head. Additionally, it can be used in the areas of personalized patient dose management, and protocol optimization and clinician training.</p> / Dissertation