Research suggests that plaque morphology plays a crucial role in determining plaque vulnerability. However the relationship between plaque morphology and rupture is still not clearly understood due to the limited information of plaque morphology. The aim of this study is to improve our understanding of the relationship between plaque morphology and rupture, and to use this to predict the risk of plaque rupture from the morphology at the molecular level. This can enable the identification of culprit lesions in clinical situations for assessing plaque rupture risk. Histological assessments were carried out on 18 carotid plaque specimens. The 3-D collagen, lipid and macrophage distributions along the entire length of the plaque were analysed in both ruptured and non-ruptured symptomatic plaques. In addition, plaque morphology on the rupture sites were examined and compared with the surrounding regions. It was found that ruptured plaques had thinner fibrous caps and larger lipid cores compared to non-ruptured plaques. Also, ruptured plaques had lower collagen content compared to non-ruptured plaques, and higher collagen contents upstream compared to downstream region from the plaque throat. At the rupture site there was lower collagen content, and a larger lipid core thickness behind a thin fibrous cap compared with the mean for the longitudinally adjacent and circumferential regions. Macrophage cells were located nearer to the boundary of the luminal wall in ruptured plaques. For both groups, the area occupied by macrophages is greater at the upstream shoulder of the plaque. There is a positive correlation between macrophage area and lipid core area, a negative correlation between macrophage area and collagen content, and between lipid core size and collagen content for both plaque groups. 3D reconstruction of ex-vivo specimens of carotid plaques were carried out by a combined analysis of US imaging and histology. To reconstruct accurate 3D plaque morphology, the non-linear tissue distortion in histological images caused by specimen preparation was corrected by a finite element (FE) based deformable registration procedure. This study shows that it is possible to generate a 3D patient specific plaque model using this method. In addition, the study also quantitatively assesses the tissue distortion caused by histological procedures. It shows that at least 30% tissue shrinkage is expected for plaque tissues. The histology analysis result was also used to evaluate ultrasound (US) tissue characterization accuracy. An ex-vivo 2D ultrasound scan set-up was used to obtain serial transverse images through an atherosclerotic plaque. The different plaque component region obtained from ultrasound images was compared with the associated histology result and photograph of the sections. Plaque tissue characterisation using ex-vivo US can be performed qualitatively, whereas lipid core assessment from ultrasound scan can be semi-quantitative. This finding combined with the negative correlation between lipid core size and collagen content, suggests the ability of US to indirectly quantify plaque collagen content. This study may serve as a platform for future studies on improving ultrasound tissue characterization, and may also potentially be used in risk assessment of plaque rupture.

Cold pressed Hemp (Cannabis sativa L) seed oil, which contains a favorable ratio of omega-6/omega-3 and a considerable amount of vitamin E, is a high nutrition value product with various health benefits. However, the presence of a large amount of chlorophyll makes the oil highly susceptible to photo-oxidation and limits its applications. Chlorophyll and other pigments in edible oils are commonly reduced through oil bleaching process. The objective of this study was to reduce the chlorophyll content in cold pressed hemp seed oil using ultrasonic bleaching and evaluate the impacts on carotene content, peroxide value, conjugated diene, total phenolic content and oxidative stability. The bleaching efficiency increased significantly as the ultrasound power (0 to 60% pressure amplitude) and concentration of bleaching clay (20 to 40 g/kg) increased. At 20% ultrasound power, the chlorophyll reduction (%) of different clays was found to be 99.4% (industrial clay) > 97.8% (activated bentonite) > 82.7% (sepiolite) > 47.1% (non-activated bentonite). Ultrasonic bleaching significantly reduced (p<0.05) the total chlorophyll content, total carotene content and primary oxidation products of hemp seed oil. During accelerated oxidation tests (40 and 60 ℃), the developments of peroxide value and conjugated diene were significantly (p<0.05) slower for hemp seed oil treated with ultrasonic bleaching compared to the control oil. Enhanced oxidative stability was observed in hemp seed oil after ultrasonic bleaching. In addition, another objective of this study was to evaluate the impacts of solvent and heat treatment on phenolic profile and antioxidant activity of cold pressed canola and hemp meals. For canola meal, a solvent-mixture of aqueous methanol (70%) and aqueous acetone (70%) in a ratio of 1:1 (v/v) extracted (p<0.05) slightly higher total phenolic content (11.3 mg SAE/g), while aqueous methanol (70%) extracts exhibited higher DPPH scavenging effect (40.4%). For hemp meal, aqueous acetone (80%) extracts exhibited higher total phenolic content (6.0 mg GAE/g) and DPPH scavenging effect (12.5%). Total phenolic content and antioxidant activity in canola meal extracts were significantly higher (p<0.05) than those in hemp meal extracts. After heat treatments at temperature from 140 to 180 ℃, canola and hemp meal extracts showed equal or lower total phenolic content and DPPH scavenging effect. / May 2017

Les ultrasons focalisés de haute intensité (HIFU) guidés par IRM et combinés à la thermométrie basée sur la fréquence de résonance du proton (PRF) sont une technique prometteuse pour l’ablation non invasive de tumeurs, le dépôt local de médicaments et l’activation des transgènes. Ce travail présente de nouveaux développements dans le domaine de la thermométrie PRF en présence de mouvement physiologique périodique associé aux variations du champ magnétique. De nouvelles stratégies de correction sont proposées et exploitent la méthode multi-baseline établie en incluant un modèle de variation de phase. Elles sont illustrées avec des exemples de thermométrie dans le sein et dans le cœur humain. De plus, d’autres facteurs influençant la thermométrie PRF, notamment la présence de graisse dans le sein et le flux sanguin dans le cœur, sont étudiés. Dans la seconde partie de ce travail a été abordée la problématique du contrôle précis de la température. Une première approche propose un algorithme de contrôle proportionel, intégral et dérivatif (PID) amélioré utilisant des paramétres de contrôle adaptatifs. En étendant ce concept à un contrôle 3D de la température, une implémentation de chauffage volumétrique est proposée. Par ailleurs, une nouvelle méthode de repositionnement dynamique de la coupe d’imagerie permet de fournir des informations volumétriques sur l’anatomie et la température en temps réel. La combinaison avec la compensation 2D de mouvement et l’adaptation du faisceau ultrasonore permet la réalisation d’un chauffage volumétrique suivant une courbe de température ou de dose thermique prédéfinie qui fonctionne même en présence de mouvements. / MR-guided high-intensity focused ultrasound (HIFU) using proton resonance frequency (PRF) based thermometry is a promising technique for non-invasive ablations in tumor therapy as well as for targeted drug delivery and the activation of transgenes. This work presents further developments in the field of PRF thermometry in the presence of periodical physiological motion and the associated magnetic field variations. Using the examples of thermometry in the human breast and the human heart, new correction strategies are presented which extend the established multi-baseline phase correction to include a model of the phase variation and external sensor readings from a pencil-beam navigator. In addition further factors, namely the presence of fat in the breast and blood flow in the heart influencing the performance of MR thermometry in these organs are examined.In the second part of this work, the issue of precise temperature control has been approached in two ways. First, an improved proportional, integral and derivative (PID) controller using adaptive control parameters is developed. By expanding the concept of temperature control to 3D, an implementation of volumetric heating is presented. A novel slice sweep technique provides volumetric anatomic and temperature information in near-real time. The combination with 2D motion compensation and adaptation of the ultrasound beam position allows to achieve volumetric heating according to a pre-defined target temperature or thermal dose value even in the presence of motion.

Understanding cardiac pumping function is crucial to guiding diagnosis, predicting outcomes of interventions, and designing medical devices that interact with the cardiovascular system.  Computer simulations of hemodynamics can show how the complex cardiovascular system is influenced by changes in single or multiple parameters and can be used to test clinical hypotheses. In addition, methods for the quantification of important markers such as elevated arterial stiffness would help reduce the morbidity and mortality related to cardiovascular disease. The general aim of this thesis work was to improve understanding of cardiovascular physiology and develop new methods for assisting clinicians during diagnosis and follow-up of treatment in cardiovascular disease. Both computer simulations and medical imaging were used to reach this goal. In the first study, a cardiac model based on piston-like motions of the atrioventricular plane was developed. In the second study, the presence of the anatomical basis needed to generate hydraulic forces during diastole was assessed in heathy volunteers. In the third study, a previously validated lumped-parameter model was used to quantify the contribution of arterial and cardiac changes to blood pressure during aging. In the fourth study, in-house software that measures arterial stiffness by ultrasound shear wave elastography (SWE) was developed and validated against mechanical testing. The studies showed that longitudinal movements of the atrioventricular plane can well explain cardiac pumping and that the macroscopic geometry of the heart enables the generation of hydraulic forces that aid ventricular filling. Additionally, simulations showed that structural changes in both the heart and the arterial system contribute to the progression of blood pressure with age. Finally, the SWE technique was validated to accurately measure stiffness in arterial phantoms. / <p>QC 20161115</p>

Empirical tests developed for an objective evaluation of noodle texture as well as sensory methods provide no information about the rheological parameters responsible for differences in the texture of Asian noodles. Therefore, there is a need for a technique to evaluate the rheological properties of Asian noodles that is fast, easy and inexpensive. Promising results from ultrasonic assessments of the rheological properties of wheat flour doughs and preliminary noodle studies were an encouragement to use ultrasound to address such need in this thesis. Using ultrasound at a relatively high frequency (1.4 MHz), the rheological properties of raw noodles made with three Canadian wheat varieties at various barley β-glucan (BBG) contents, sheeting work input levels and salt to kansui ratios (formulas) were evaluated. Conventional rheological, i.e., stress relaxation (SR) and uniaxial extension (Kieffer), measurements were employed for comparison purposes. The capability of ultrasound for evaluating the effects of BBG addition and sheeting work input on the rheological properties of raw wheat noodles of this study was confirmed. A greater sensitivity of ultrasound to microscopic changes in noodle dough structure, compared to SR and Kieffer tests, was reflected in differences between the results of ultrasound and those of the SR and Kieffer tests with respect to the influences of flour variety and formula on noodle rheology. Investigations of the density of raw noodles showed that air bubbles were present in the noodle dough matrix. A simple, fast and low-cost method, based on the measurement of noodle dough dimensions during the sheeting process, was proposed for a quick evaluation of noodle dough rheology. The results of the proposed method were in agreement with those of conventional rheological measurements on the effects of flour variety and sheeting work input on noodle texture. The time-dependent effect of kansui on noodle dough structure was confirmed by comparing the results of this new method with those of SR and Kieffer tests with respect to the effect of formula on noodle rheology. Further investigations are proposed to establish this method for quick assessment of Asian wheat noodle rheology. / February 2017

<p>In this thesis, we develop methods for addressing the deficiencies of array processing with linear thinned arrays. Our methods are designed for array systems mounted on moving platforms and exploit synthetic aperture processing techniques. In particular, we use array motion to decrease the sidelobe levels and increase the degrees of freedom available from thinned array systems. In this work, we consider two application areas 1) passive SONAR and 2) ultrasound imaging. </p><p>Synthetic aperture processing is a methodology for exploiting array motion and has been successfully used in practice to increase array resolution. By spatially sampling along the path of the array virtual sensors can be realized and coherently fused to the existing array. The novel contribution of this work is our application of synthetic aperture processing. Here our goal is not to increase array resolution, instead we propose to use the synthetic aperture process to expand the spatial covariance and spatial frequency sensing capabilities of thinned array system.</p><p> </p><p>In the passive sensing case, we use a class of thinned arrays know as co-prime linear sensor arrays for source localization. The class of co-prime arrays provides roughly half the aperture worth of spatial covariances and with modest array motion can be extended to the full aperture of the array. The amount of motion required to produce a full set of spatial covariances is shown to be a function of the co-prime array parameters and is only a fraction of the total aperture of the array. The full set of spatial covariances can be used to form a spatial covariance matrix with dimension equal to that of a uniform array. With a spatial covariance matrix in hand one can perform signal processing tasks as if the array were fully populated. Three methods for spatial covariance matrix estimation are compared in different source localization scenarios. In the work presented here, we demonstrate the benefits of our approach for achieving reduced sidelobe levels and extending the source localization capabilities above the limits of the static co-prime array. </p><p>In the active sensing case, we develop a framework for incorporating motion using thinned arrays for ultrasound imaging. In this setting, array motion is used to augment the spatial frequency sensing capabilities of the thinned array system. Here we develop an augmentation strategy based on using quarter-wavelength array translations to fill-in missing spatial frequencies not measured by the static thinned array. The quarter-wavelength translation enables the thinned array system to sample missing spatial frequencies and increase the redundancy of other spatial frequencies sampled by the array. We compare the level of redundancy in sampling the spatial frequencies achieved by the thinned arrays post translation to different levels of sample redundancy derived from pruning the transmit/receive events of a uniform array. In this manner, we are able to examine how the level of spatial frequency redundancy afforded by different thinned arrays compare over the full redundancy range of the uniform array. While artificially pruning the uniform array does not necessarily create realizable arrays, it provides the means to compare image quality at different spatial frequency redundancy levels. In this work, we are able to conclude that images formed from thinned arrays using the translated synthetic aperture process are capable of approximating images formed from the corresponding uniform array. In particular, the systems considered in this work have approximately one-third of the active sensors when compared to the uniform array. </p><p>In both application areas, the use of thinned arrays offers a reduction in the cost to deploy and maintain a given array system. The feature that makes it possible to overcome the spatial sampling deficiencies of thinned array systems is motion and it is at the core of the performance gains in these applications.</p> / Dissertation

Ultrasound-based fetal biometry is used to derive important clinical information for identifying IUGR (intra-uterine growth restriction) and managing risk in pregnancy. Accurate and reproducible biometric measurement relies heavily on a good standard image plane. However, qualitative visual assessment, which includes the visual identification of certain anatomical landmarks in the image is prone to inter- and intra-reviewer variability and is also time-consuming to perform. Automated anatomical structure detection is the first step towards the development of a fast and reproducible quality assessment of fetal biometry images. This thesis deals specifically with abdominal scans in the development and evaluation of methods to automatically detect the stomach and the umbilical vein within them. First, an original method for detecting the stomach and the umbilical vein in fetal abdominal scans was developed using a machine learning framework. A classifier solution was designed with AdaBoost learning algorithm with Haar features extracted from the intensity image. The performance of the new method was compared on different clinically relevant gestational age groups. Speckle and the low contrast nature of ultrasound images motivated the idea of introducing features extracted from local phase images. Local phase is contrast invariant and has proven to be useful in other ultrasound image analysis application compared with intensity. Nevertheless, it has never been implemented in a machine learning environment before. In our second experiment, local phase features were proven to have higher discriminative power than intensity features which enabled them to be selected as the first weak classifiers with large classifier weight. Third, a novel approach to improving the speed of the detection was developed using a global feature symmetry map based on local phase to select the candidate locations for the stomach and the umbilical vein. It was coupled with a local intensity-based classifier to form a “hybrid” detector. A nine-fold increase in the average computational speed was recorded along with higher accuracy in the detection of both the anatomical structures. Quantitative and qualitative evaluations of all the algorithms were presented using 2384 fetal abdominal images retrieved from the image database study of the Oxford Ultrasound Quality Control Unit of the INTERGROWTH-21st project. Finally, the “hybrid” detection method was evaluated in two potential application scenarios. The first application was clinical scoring in which both the computer algorithm and four experts were asked to record presence or absence of the stomach and the umbilical vein in 400 ultrasound images. The computer-experts agreement was found to be comparable with the inter-expert agreement. The second application concerned selecting the standard image plane from 3D abdominal ultrasound volume. The algorithm was successful in selecting 93.36% of the images plane defined by the expert in 30 ultrasound volumes.

Vitamin D is very important for endochondral ossification and it is commonly insufficient during pregnancy (Javaid et al., 2006). Insufficiency of vitamin D during pregnancy predicts bone mass and hence predicts adult osteoporosis (Javaid et al., 2006). The relationship between maternal vitamin D and manually measured fetal biometry has been studied (Mahon et al., 2009). However, manual fetal biometry especially volumetric measurements are subjective, time-consuming and possibly irreproducible. Computerised measurements can overcome or at least reduce such problems. This thesis concerns the development and evaluation of novel methods to do this. This thesis makes three contributions. Firstly, we have developed a novel technique based on the Random Forests (RF) classifier to segment and measure several fetal femoral characteristics from 3D ultrasound volumes automatically. We propose a feature selection step in the training stage to eliminate irrelevant features and utilise the "good" ones. We also develop a weighted voting mechanism to weight tree probabilistic decisions in the RF classifier. We show that the new RF classifier is more accurate than the classic method (Yaqub et al., 2010b, Yaqub et al., 2011b). We achieved 83% segmentation precision using the proposed technique compared to manually segmented volumes. The proposed segmentation technique was also validated on segmenting adult brain structures in MR images and it showed excellent accuracy. The second contribution is a wavelet-based image fusion technique to enhance the quality of the fetal femur and to compensate for missing information in one volume due to signal attenuation and acoustic shadowing. We show that using image fusion to increase the image quality of ultrasound images of bony structures leads to a more accurate and reproducible assessment and measurement qualitatively and quantitatively (Yaqub et al., 2010a, Yaqub et al., 2011a). The third contribution concerns the analysis of data from a cohort study of 450 fetal femoral ultrasound volumes (18-21 week gestation). The femur length, cross-sectional areas, volume, splaying indices and angles were automatically measured using the RF method. The relationship between these measurements and the fetal gestational age and maternal vitamin D was investigated. Segmentation of a fetal femur is fast (2.3s/volume), thanks to the parallel implementation. The femur volume, length, splaying index were found to significantly correlate with fetal gestational age. Furthermore, significant correlations between the automatic measurements and 10 nmol increment in maternal 25OHD during second trimester were found.

Chronic lower back pain is a major public health problem, with direct and indirect economic costs comparable to those of heart disease, depression and diabetes. In many cases this pain derives from degeneration of the intervertebral disc (IVD), a fibrous, avascular tissue that sits between the vertebrae in the spinal column. A novel treatment approach for this ‘discogenic’ pain is the injection of a hydrogel that hybridises in situ and restores the normal biomechanical function of the disc. While a number of promising materials are currently under development, existing approaches to removing degenerate material from the disc prior to injection are invasive and compromise the structural integrity of the disc. Mechanical fractionation of the tissue using acoustic cavitation generated by high intensity focussed ultrasound (HIFU) has the potential to be non-invasive, and to enhance the effectiveness of the procedure by preserving the outer regions of the disc. The primary goal of this thesis is to investigate the feasibility of this approach. The acoustic properties of the disc were first measured using a modified scanning acoustic microscope. The outer region of the disc, the annulus fibrosus (AF) was found to be highly attenuative compared to the central nucleus pulposus (NP). These measured properties were then used in a simplified two-dimensional model to simulate the shape of the acoustic pressure field within the disc. A configuration using two confocal spherically focussed 0.5 MHz single-element transducers was able to produce a tightly focused field suitable for use in the IVD. As preliminary experiments suggested that high pressure amplitudes were required to initiate cavitation inside the disc, the use of exogenous nuclei to lower this threshold was investigated. A novel class of solid sonosensitive nanoparticles (SNPs) suitable for use in the IVD were developed and characterised. These SNPs comprise a layer of hydrophobic silica particles deposited onto a polystyrene core, and are thought to trap small gas pockets in surface crevices. Coated particles were found to reduce the cavitation threshold significantly in both water and blood, from some 2.0 - 2.5 MPa at 1.067 MHz to below 1.0 MPa. The particles were also found to provide repeatable initiation of cavitation activity during prolonged or repeated exposures, and to exhibit good storage stability, suggesting that they they may be appropriate for use within the IVD. Finally, a combined therapy and monitoring system was designed, built and validated. The system comprised two confocal 0.5 MHz spherically focussed HIFU transducers with central openings, each co-axially aligned with either a single element passive cavitation detector or a 64-element array that could be used for both active and passive imaging. The system was found to be capable of initiating inertial cavitation in the disc at pressures as low as 2.5MPa in the presence of sonosensitive nanoparticles. Use of the array in active mode enables creation of a B-mode image that provides anatomical information on the boundaries of the IVD, whist the same array could be used for passive mapping of acoustic emissions arising fromthe HIFU focus during therapy. Two different exposure regimes were found to be capable of producing sizeable perforations within the NP without significantly damaging the AF, and preliminary investigations were carried out into themechanism of damage. The location and extent of cavitation as seen on passive maps acquired during treatment was found to coincide with the regions of NP fractionation. This confirms that passive acoustic mapping can provide the real-time treatment monitoring necessary to ensure both safety and efficacy of ultrasonic IVD fractionation. Prior to clinical application, a significant amount of further development is required to further validate non-invasive disc fractionation by HIFU and the subsequent steps for minimally invasive disc replacement using injectable hydrogels. The present work has nonetheless demonstrated for the first time that minimally invasive removal of degenerate disc tissue is feasible trough the combined use of sonosensitive nanoparticles and a relatively low-cost therapeutic ultrasound system that provides simultaneous anatomical imaging and real-time treatment monitoring by passive acoustic mapping.

Background: Previous research suggests that vitamin D deficiency during pregnancy may be associated with suboptimal fetal growth, but direct evidence is lacking. Our objectives were 1) to develop a method for measurement of the fetal sphenoidal fontanelle area (FA) and femur volume (FV) using 3D ultrasound; 2) to create normal charts for FA and FV; and 3) to correlate FA and FV with maternal vitamin D concentration. Methods: FA measurement in 3D was evaluated in vitro and in vivo. Different segmentation methods for FV measurement were explored. A novel FV method was described which consists of three linear measurements and a volume equation; this was validated in vitro and also by comparing FV measured sonographically to the true volume assessed by computed tomography (CT), in 6 cases following pregnancy termination. A cohort of 868 uncomplicated pregnancies was selected on the basis of strict inclusion criteria; participants underwent serial ultrasound scans for FV and multilevel modeling was used for the creation of a “prescriptive” FV chart. Finally, a different cohort of 357 healthy pregnant women had serum vitamin D levels and FV ultrasound at 34 weeks gestation and dual emission x-ray absorptiometry (DEXA) of their neonates in order to investigate the prenatal determinants of fetal bone mass. Results: FA measurement was accurate in vitro, but unreliable in vivo and was therefore abandoned. A novel FV method had excellent agreement with CT and superior repeatability compared with segmentation-based methods. A normal FV chart was created and the regression equations for the median and percentile values were presented. Vitamin D demonstrated a significant correlation with FV. Conclusions: FV is a reliable sonographic marker of skeletal growth. Maternal vitamin D deficiency is associated with reduced FV. This finding has public health implications as reduced bone mass may increase the lifetime risk of osteoporosis, through fetal programming.