Thesis (Ph. D.)--University of Washington, 1990. / Vita. Includes bibliographical references (leaves [174]-182).

Thesis (M.S.) University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on August 28, 2007) Vita. Includes bibliographical references.

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.

This thesis forms part of an ongoing long-term project to investigate the suitability of Doppler optical coherence tomography (OCT) as a measurement tool to investigate skin thickness and blood flow in patients with systemic sclerosis. There is a discussion of the characterisation of an electro-optic phase modulator for use in a Doppler OCT imaging system which is being built for the purpose of clinical studies. In addition to this the development of software for the same system is described. The work includes a comparison of two methods of obtaining Doppler information that were tested with the system; a phase resolved method and a correlation mapping method. Initial structural and Doppler images obtained using the system are presented. In addition to this the development of semi-automated software to measure skin thickness from both OCT and high frequency ultrasound images is discussed. The results of a study, for which this software was developed, into skin thickness measurements using both techniques in both patients with systemic sclerosis and healthy controls are presented. Both OCT and high frequency ultrasound were able to measure a statistically significant difference in epidermal thickness at multiple locations on the body. Finally, the modification of a freely available Monte Carlo simulation for light propagation in multi-layered tissue (MCML) to enable the simulation of structural and Doppler OCT images is covered. The simulation was able to extract the magnitude of the simulated flow accurately to within an order of magnitude, and after a simple filter was applied to eliminate fluctuations in the data the structure of the Doppler image closely matched what was modelled.

Simulative tests, such as asphalt pavement analyzer (APA), Hamberg rut tester etc. have been widely used to evaluate the performance of asphalt mixtures. However, simulative tests to evaluate the performance of the mixtures cannot give fundamental properties of Asphalt Concrete (AC) due to the complex stress and strain fields. On the other hand, due to the availability of high-performance computing systems and software, numerical techniques are gaining popularity. This dissertation presents a computational simulation method of the APA tests in order to evaluate the rutting potential of asphalt mixtures based on actual microstructure reconstructed from X-ray tomography images. In the study, the microstructure of AC is obtained through the analysis of X-ray images, which included the digital information of the microstructure for the scanned specimen. In the simulations the three phases, mastic (asphalt binder with mineral filler), aggregates, and voids are assigned with different material properties. Aggregates are modeled as an elastic material, and air voids are removed during the loading steps. The adopted two-layer model is only used to represent the rate and temperature dependent behavior of the mastics. The parameters are obtained with inverse methods. Based on the sensitivity analysis of the parameters, an iterative procedure is performed to optimize the parameters using the experimental measurement and results of the model simulations. A parametric study is also conducted to study the effect of major parameters such as the stiffness ratio of the networks on the macro response of the model. The simulation results obtained shows a good agreement with the experimental results. The dissertation also presents a method to measure micro strains in asphalt mixture. An automated procedure using tomography images to reconstruct three-dimensional particles is developed. The translations of the particles are obtained from the coordinate differences of particles' mass centers before and after the APA testing. The micro and macro strains in the mixture are calculated based on the particle translations. A good correlation is found between measured strains and experimental result. / Ph. D.

To confirm the presence of prostate cancer which is the most incident visceral cancer in men, prostate biopsies are acquired using the magnetic resonance imaging fusion-guided prostate biopsy protocol. For this approach annotated magnetic resonance imaging is overlaid onto real-time ultrasound imaging to guide sampling of suspicious regions marked by uroradiologists. Additional biopsy samples are acquired via the previous clinical gold standard, i.e. the templated 12-core transrectal ultrasound-guided prostate biopsy protocol. While this approach improves the sensitivity of the prostate biopsy, a real-time, multiparametric imaging method of identifying biopsy targets could help overcome some of the inherent pitfalls of the magnetic resonance imaging fusion-guided prostate biopsy. Since ultrasound is used during the prostate biopsy, photoacoustic tomography, e.g. a hybrid imaging modality in which clinical ultrasound probes can be used to detect centimeters deep chemical alterations, has the potential to provide real-time targeting during biopsy. The translation of photoacoustic tomography to the clinic for prostate biopsy has been prevented by engineering challenges, which include identification of a biomarker for detecting suspicious regions of tissue and light delivery to the prostate for photoacoustic signal generation. Here, we present a vascular texture analysis method that identified 100% of primary and 67% of secondary tumors in the testing data set of ex vivo human prostate specimens. This method can be applied to future in vivo photoacoustic and ultrasound tomography of human prostates after further optimization of light delivery for photoacoustic tomography. To progress towards achieving this aim, we developed a transurethral light delivery device with angular light coupling method. By controlling the launch angle of the light into the fiber, the conversion of forward to side propagating energy can be improved from 27% to 98%, and the longitudinal emission profile can be controlled in order to illuminate the whole prostate simultaneously.<br>

Genitourinary cancer refers to the presence of tumours in the genital or urinary organs such as bladder, kidney and prostate. In 2008 the worldwide incidence of bladder cancer was 382,600 with a mortality of 150,282. Radiotherapy is one of the main treatment choices for genitourinary cancer where accurate delineation of the gross tumour volume (GTV) on computed tomography (CT) images is crucial for the success of this treatment. Limited CT resolution and contrast in soft tissue organs make this difficult and has led to significant inter- and intra- clinical variability in defining the extent of the GTV, especially at the junctions of different organs. In addition the introduction of new imaging techniques and modalities has significantly increased the number of the medical images that require contouring. More advanced image processing is required to help reduce contouring variability and assist in handling the increased volume of data. In this thesis image analysis methodologies were used to extract low-level features such as entropy, moment and correlation from radiotherapy planning CT images. These distinctive features were identified and used for defining the GTV and to implement a fully-automatic contouring system. The first key contribution is to demonstrate that second-order statistics from co-occurrence matrices (GTSDM) give higher accuracy in classifying soft tissue regions of interest (ROIs) into GTV and non-GTV. Loadings of the principal components (PCs) of the GTSDM features were found to be consistent over different patients. Exhaustive feature selection suggested that entropies and correlations produced consistently larger areas under receiver operating characteristic (AUROC) curves than first-order features. The second significant contribution is to demonstrate that in the bladder-prostate junction, where the largest inter-clinical variability is observed, the second-order principal entropy from stationery wavelet denoised CT images (DPE) increased the saliency of the bladder prostate junction. As a result thresholding of the DPE produced good agreement between gold standard clinical contours and those produced by this approach with Dice coefficients. The third contribution is to implement a fully automatic and reproducible system for bladder cancer GTV auto-contouring based on classifying second-order statistics. The Dice similarity coefficients (DSCs) were employed to evaluate the automatic contours. It was found that in the mid-range of the bladder the automatic contours are accurate, but in the inferior and superior ends of bladder automatic contours were more likely to have small DSCs with clinical contours, which reconcile with the fact of clinical variability in defining GTVs. A novel male bladder probability atlas was constructed based on the clinical contours and volume estimation from the classification results. Registration of the classification results with this probabilistic atlas consistently increases the DSCs of the inferior slices.

Thesis (M.S.) -- Worcester Polytechnic Institute. / Keywords: Hypothesis testing; motion compensation; SPECT. Includes bibliographical references (leaves 30-31).

<div>This thesis compiles my work on three projects.</div><div>The first project studies the cancellation of singularities in the inversion of two X-ray type transforms in the presence of conjugate points. The second project studies the recovery of singularities for the weighted cone transform. The third project studies the phenomenon of Rayleigh waves and Stoneley waves in the isotropic elastic wave equation of variable coefficients with a curved boundary.</div>

Diffuse Optical Tomography is a diagnostic imaging modality where optical parameters such as absorption coefficient, scattering coefficient and refractive index distributions are recovered to form the internal tissue metabolic image. Near-infrared (NIR) light has the potential to be used as a noninvasive means of diagnostic imaging within the human breast. Due to the diffusive nature of light in tissue, computational model-based methods are required for functional imaging. The main goal is to recover the spatial variation of optical properties which shed light on the different metabolic states of tissue and tissue like media. This thesis addresses the issue of quantitative recovery of optical properties of tissue-mimicking phantom and pork tissue using diffuse optical tomography (DOT). The main contribution of the present work is the development of robust, efficient and fast optical property reconstruction algorithms for a direct 3-D DOT imaging system. There are both theoretical and experimental contributions towards the development of an imaging system and procedures to minimize accurate data collection time, overall system automation as well as development of computational algorithms. In nurturing the idea of imaging using NIR light into a fully developed direct 3-D imaging system, challenges from the theoretical and computational aspects have to be met. The recovery of the optical property distribution in the interior of the object from the often noisy boundary measurements on light, is an ill-posed ( and nonlinear) problem. This is particularly true, when one is interested in a direct 3-D image reconstruction instead of the often employed stacking of 2-D cross-sections obtained from solving a set of 2-D DOT problems. In order to render the DOT, a useful diagnostic imaging tool and a robust reconstruction procedure giving accurate and reliable parameter recovery in the scenario, where the number of unknowns far outnumbers the number of independent data sets that can be gathered (for example, the direct 3-D recovery mentioned earlier) is essential. Here, the inversion problem is often solved through iterative methods based on nonlinear optimization for the minimization of a data-model misfit function. An interesting development in this direction has been the development of Broyden’ s and adjoint Broyden’ s methods that avoids direct Jacobian computation in each iteration thereby making the full 3-D a reality. Conventional model based iterative image reconstruction (MoBIIR) algorithm uses Newton’ s and it’s variant methods, where it required repeated evaluation of whole Jacobian, which consumes bulk time in reconstruction process. The explicit secant and adjoint information based fast 2-D/3-D image reconstruction algorithms without repeated evaluation of the Jacobian is proposed in diffuse optical tomography, where the computational time has been decreased many folds by updating the Jacobian successively through low rank update. An alternative route to the iterative solution is attempted by introducing an artificial dynamics in the system and treating the steady-state response of the artificially evolving dynamical system as a solution. The objective is to consider a novel family of pseudo-dynamical 2-D and 3-D systems whose numerical integration in time provides an asymptotic solution to the inverse problem at hand. We convert Gauss-Newton’ s equation for updates into a pseudo-dynamical (PD) form by explicitly adding a time derivative term. As the pseudo-time integration schemes do not need such explicit matrix inversion and depending on the pseudo-time step size, provides for a layer of regularization that in turn helps in superior quality of 2-D and 3-D image reconstruction. A cost effective frequency domain Matlab based 2-D/3-D automated imaging system is designed and built. The complete instrumentation (including PC-based control software) has been developed using a single modulated laser source (wavelength 830nm) and a photo-multiplier tube (PMT). The source and detector fiber change their positions dynamically allowing us to gather data at multiple source and detector locations. The fiber positions are adjusted on the phantom surface automatically for scanning variable size phantoms. A heterodyning scheme was used for reading out the measurement using a lock-in-amplifier. The Matlab program carries out sequence of actions such as instrument control, data acquisition, data organization, data calibration and reconstruction of image. The Gauss-Newton’ s, Broyden’ s, adjoint Broyden’ s and pseudo-time integration algorithms are evaluated using the simulation data as well as data from the experimental DOT system. Validation of the system and the reconstruction algorithms were carried out on a real tissue, a pork tissue with an embedded fat inhomogeneity. The results were found to match the known parameters closely.