Neointimal hyperplasia, the proliferative growth of the innermost layer of the blood vessel wall, is a key process in the response to vascular injury, underlying conditions such as post-interventional restenosis and vein/arterial graft disease. One of the many mediators implicated in this process is endothelin-1 (ET-1), a potent vasoconstrictor with pro-inflammatory and pro-mitogenic actions, which acts through ETA and ETB receptor subtypes. It is well established that ET-1 increases, and ETA blockade reduces, neointima formation following vascular injury. The role of ETB is less clear because these receptors mediate potentially beneficial actions in endothelial cells (EC; such as nitric oxide production, and ET-1 clearance) but detrimental effects elsewhere (such as vascular smooth muscle) and it has been recently reported that non-cell-specific ETB deficiency is associated with increased neointimal lesion size following injury. The work described in this thesis addressed the hypothesis that endogenous ET-1 contributes to neointimal hyperplasia by activation of the ETA receptor, and that this action is moderated by concurrent activation of the ETB receptor expressed in EC. The role of ET receptors in neointimal lesion development was assessed using two models of femoral arterial injury in the mouse: (i) an established method of intraluminal wire-injury, and (ii) adaptation of a model of ligation injury that induces robust neointimal lesion formation without physical damage to the endothelium. Lesion development was assessed using standard histological techniques and this was augmented by development of quantitative optical projection tomography (OPT) to allow three-dimensional analysis of lesions. The role of ETA and ETB receptors in these models was addressed using suitable pharmacological ET receptor antagonists. Following wire-injury, selective ETB blockade (A192621; 30mg.kg-1.day-1; 35 days) increased lesion size and blood pressure without significant altering lesion composition. In contrast, selective ETA blockade (atrasentan; 10mg.kg-1.day-1; 35 days) reduced lesion size and blood pressure. Combined ETA+ETB antagonism had no effect on lesion size, despite reducing blood pressure, and reducing collagen content of the lesions. In the ligation model, neither ETA selective, ETB selective nor ETA+ETB blockade altered lesion size as assessed by standard histology but analysis by OPT indicated that ETA blockade, with or without concurrent ETB blockade, reduced lesion volume. The influence of ETB receptors expressed by ECs on lesion formation was addressed using EC-specific ETB knockout mice. Small vessel myography indicated that endothelium-dependent relaxation was unaltered in femoral arteries from these mice. In addition, no effect on lesion size or rate of development was observed in either wire- or ligation-injury models of neointima formation (although subtle effects on lesion and medial composition were apparent after intra-luminal injury). These results indicate that ETB receptor activation can moderate the detrimental actions of the ETA receptor on neointimal lesion progression, and that this role is dependent on the mode of vascular injury. Furthermore, in this setting, this beneficial action is not primarily mediated by ETB expressed by EC, suggesting that ETB in other cell types can reduce lesion development through another, unidentified mechanism. Therefore, while both ETA selective and non-selective ETA/B antagonists are currently in clinical use, in conditions where similar arterial remodelling processes occur, selective ETA receptor antagonists might be preferred.

Coded-aperture imaging offers a method of classical tomographic imaging by encoding the distance of a point from the detector by the lateral scale of the point response function. An estimate, termed a layergram, of the transverse sections of the object can be obtained by performing a simple correlation operation on the detector data. The estimate of one transverse plane contains artifacts contributed by source points from all other planes. These artifacts can be partially removed by a nonlinear algorithm which incorporates a priori knowledge of total integrated object activity per transverse plane, positivity of the quantity being measured, and lateral extent of the object in each plane. The algorithm is iterative and contains, at each step, a linear operation followed by the imposition of a constraint. The use of this class of algorithms is tested by simulating a coded-aperture imaging situation using a one-dimensional code and two-dimensional (one axis perpendicular to aperture) object. Results show nearly perfect reconstructions in noise-free cases for the codes tested. If finite detector resolution and Poisson source noise are taken into account, the reconstructions are still significantly improved relative to the layergram. The algorithm lends itself to implementation on an optical-digital hybrid computer. The problems inherent in a prototype device are characterized and results of its performance are presented.

A Varian 4 MeV isocentric therapy accelerator has been modified to perform also as a CT scanner. The goal is to provide low cost computed tomography capability for use in radiotherapy. The system will have three principal uses. These are (i) to provide 2- and 3-dimensional maps of electron density distribution for CT assisted therapy planning, (ii) to aid in patient set up by providing sectional views of the treatment volume and high contrast scout-mode verification images and (iii) to provide a means for periodically checking the patients anatomical conformation against what was used to generate the original therapy plan. The treatment machine was modified by mounting an array of detectors on a frame bolted to the counter weight end of the gantry in such a manner as to define a 'third generation' CT Scanner geometry. The data gathering is controlled by a Z-80 based microcomputer system which transfers the x-ray transmission data to a general purpose PDP 11/34 for processing. There a series of calibration processes and a logarithmic conversion are performed to get projection data. After reordering the projection data to an equivalent parallel beam sinogram format a convolution algorithm is employed to construct the image from the equivalent parallel projection data. Results of phantom studies have shown a spatial resolution of 2.6 mm and an electron density discrimination of less than 1% which are sufficiently good for accurate therapy planning. Results also show that the system is linear to within the precision of our measurement (≈ .75%) over a wide range of electron densities corresponding to those found in body tissues. Animal and human images are also presented to demonstrate that the system's imaging capability is sufficient to allow the necessary visualization of anatomy.

This dissertation presents the results of an investigation into the performance characteristics of a unique hemispherical SPECT (single-photon emission computed tomography) imaging system capable of producing three-dimensional (3D) tomographic images of the human brain. The system is completely stationary and collects all necessary views of the patient simultaneously, with no system motion. The imager consists of twenty small (10cm x 10cm crystal area), digital gamma cameras arranged in a hemispherical pattern around the patient's head and a hemispherical lead aperture. The hemispherical aperture is positioned between the cameras and the head and contains a large number of pinholes; in this way each camera sees a number of overlapping pinhole projections of the radioactive distribution within the patient's brain. The initial investigation of the performance characteristics of a 3D SPECT system of this design were carried out using a computer simulation in which effects due to radiometry, finite pinhole size, finite detector resolution, photon noise, and object attenuation were included. We used a digital 3D brain phantom as the test object and an iterative search algorithm to perform the reconstructions. The simulations were used to compare the performance of a variety of system configurations. Based upon the results of the simulation study, we constructed a laboratory prototype of the 3D SPECT system, which we used to further characterize the expected performance of a clinical imaging system of the same design. Prior to collecting SPECT data we calibrated the imaging system, which required that we efficiently measure and store the spatially variant system response function. These calibration data were then included in the reconstructions of the SPECT phantoms that we imaged. A number of different SPECT phantoms were imaged to demonstrate the system performance. We measured a reconstructed spatial resolution of 4.8mm full-width at half-maximum and a full-system sensitivity of 36cps/μCi, where both values were measured for a point source in air located at the center of the field of view. We also describe an analysis that we performed to determine the equivalent, non-multiplexed system sensitivity; using this method, we found that the equivalent sensitivity was 79% of the measured value for the system configuration and the particular task that we investigated.

Hydraulic tomography has been tested at the field scale, lab scale and in synthetic experiments. Recently Illman and Berg have conducted studies at the lab scale. Using their data hydraulic tomography can be compared to homogeneous anisotropic solutions using one pumping well or multiple pumping wells. It has been found that hydraulic tomography out performs homogenous methods at predicting hydraulic head for validation pumping experiments. Also it has been shown in this study that homogenous anisotropic tests exhibit scenario dependent behavior. Additional tests performed to further validate the conclusions made in this experiment include spatial moment analysis, response surface analysis, and synthetic hydraulic tomography and show consistent results providing additional validation of these findings. Additional study examining the principle of reciprocity has proven inconclusive.

The properties and imaging performance of the computed tomographicimaging spectrometer (CTIS) have been investigated with Fourierand wavelet crosstalk matrices. These matrices and theircorresponding datacube reconstruction algorithms explicitly usedsensitivity equations describing the CTIS imaging system. Theseequations derived from Franhofer diffraction theory of thecomputed generated hologram (CGH) disperser, serve as themathematical model of the CTIS.The Fourier crosstalk matrix (FCTM) was primarily used to analyzethe CTIS imaging system. The FCTM describes which spatial andspectral frequencies contribute to object cube data entering thesystem and whether or not these frequencies give distinctcontributions with respect to each other. Furthermore, since theCTIS is a limited angle tomographic imaging system the missingcone of frequencies which is a feature of this instrument isclearly shown using the FCTM. Subsequently, Fourier-basedestimates of the reconstructed object cube (i.e. the datacube)will be missing this frequency information even if the CTIS is aperfect optical system.The wavelet crosstalk matrix (WCTM) was used primarily for efficient datacubereconstruction only. The datacube reconstruction calculations areprimarily proof-of-concept and reproduce the Fourier results withsome absence of Fourier related artifacts. The waveletdecomposition of the object cube is useful for studying multipleobjects in a parallel processing environment withoutreconstructing the entire datacube, thus reducing overall complexity.Datacube reconstructions of actual astronomical observations withthe CTIS, using the techniques of this research, were consistentwith previous independent datacube estimates from the same datausing existing conventional techniques. Furthermore these objectsfurnish natural point-spread functions that supplementcomputational simulations of the CTIS by describing actual imagingsystem performance.The computational tools for the study ofthe CTIS imaging system provide the additional bonus of ananalysis of object detectability by the computation of receiveroperator characteristic (ROC) curves. We used a synthetic binarystar to simulate this in the presence of both detector and objectnoise.Some suggestions for future research directions are given.

No description available.

Venous thromboembolism (VTE) is a common disease with a myriad of presentation. It is often difficult to diagnosis with symptoms which are shared with many other disorders. Because of the overlap in symptomatology with other pathologies it is both commonly overlooked when present and commonly considered when absent. The threshold for investigating suspected VTE has dropped over time, in part due to a greater awareness of the disease among clinicians, but also because of the greater availability of diagnostic tests which are both accurate at positively diagnosing VTE and are patient friendly. This has resulted in a mushrooming of the number of diagnostic tests being performed for suspected VTE in radiology departments. As such radiology provides a window into the disease in a way that no other speciality can. All branches of medicine having their share of VTE patients but radiology provides a unique opportunity to study VTE patients as, no matter from which speciality they arise when the disease is suspected, they will almost inevitably end up undergoing a definitive radiological test. There is much still to learn about VTE however developments in modern imaging and computerised databases have advanced our understanding of this common disease. The window that radiology provides into VTE has contributed towards those advances.

Seismic data from 106 station pair-paths, from the CNSN (Canadian National Seismic Network) and POLARIS (Portable Observatories for Lithospheric Analysis and Research Investigating Seismicity) seismic networks, were used to measure surface waves from earthquake events. Fundamental-mode Rayleigh-wave dispersion curves were generated and inverted to obtain dispersion maps and S-velocity cross-sections. Results show a clear distinction between the Cordilleran and cratonic lithospheres. The Cordilleran lithopshere shows a low-velocity perturbation with values ranging from -2% to -5%, while the cratonic lithosphere shows a high-velocity perturbation with values ranging from 3% to 9%. The large range in perturbation between the Cordilleran and cratonic lithospheres resolves the Cordilleran/craton boundary, showing that the boundary is present down to 200 km in depth and dips under the cratonic lithosphere. A high-velocity anomaly within the already high velocity cratonic lithosphere is present under Great Slave Lake and is interpreted as preserved Precambrian slab material. Many small high-velocity perturbations, reaching about 4%, are present at depths of 300+ km throughout the survey, and interpreted as being remnants of the Kula or Farallon plates. / February 2017

The aim of this study was to evaluate whether volumetric changes in persistent periapical lesions can be detected in follow-ups six months to five years after apicoectomy using cone-beam computed tomography. Patients with a previous treatment history of apicoectomy and for whom a pre-surgical CBCT scan was taken between November 2010 and December 2015 were invited to participate in the study. A post-surgical CBCT image of the treated tooth was obtained at the recall visit. Volumetric and linear measurements of periapical lesions on initial and postoperative CBCT images were performed using DiThreshGUI software and two calibrated examiners—a board-certified endodontist and a board-certified oral radiologist. Repeated-measures ANOVA were used to estimate the magnitude of reduction and to test for differences (at alpha=0.05). A total of 20 patients with 27 surgically treated teeth were recalled at an average interval of 37 months. Reduction in the size of lesions was observed in 24 teeth (88%); overall, the volumes significantly decreased as detected by software-assisted measurement of volume (P = .0002) and by calculation from linear measurements (P < .0001). Volumetric analysis detected a reduction of 86% in lesions while the linear-derived volume measurements yielded an average reduction of 96%. These two methods of lesion assessment were strongly correlated with one another in pre-surgical scans (r>0.88) when apical lesions are measurable.