Uncertainty in the sizing of breast cancer masses is a major issue in breast screening programs, as there is a tendency to severely underestimate the sizing of malignant masses, especially with ultrasound imaging as part of the standard triple assessment. Due to this issue about 20% of all surgically treated women have to undergo a second resection, therefore the aim of this thesis is to address this issue by developing novel image analysis methods. Ultrasound elasticity imaging has been proven to have a better ability to differentiate soft tissues compared to standard B-mode. Thus a novel segmentation algorithm is presented, employing elasticity imaging to improve the sizing of malignant breast masses in ultrasound. The main contributions of this work are the introduction of a novel filtering technique to significantly improve the quality of the B-mode image, the development of a segmentation algorithm and their application to an ongoing clinical trial. Due to the limitations of the employed ultrasound device, the development of a method to improve the contrast and signal to noise ratio of B-mode images was required. Thus, an autoregressive model based filter on the radio-frequency signal is presented which is able to reduce the misclassification error on a phantom by up to 90% compared to the employed device, achieving similar results to a state-of-the art ultrasound system. By combining the output of this filter with elasticity data into a region based segmentation framework, a computationally highly efficient segmentation algorithm using Graph-cuts is presented. This method is shown to successfully and reliably segment objects on which previous highly cited methods have failed. Employing this method on 18 cases from a clinical trial, it is shown that the mean absolute error is reduced by 2 mm, and the bias of the B-Mode sizing to underestimate the size was overcome. Furthermore, the ability to detect widespread DCIS is demonstrated.

Crystallographic texture in polycrystalline HCP and cubic materials, often developed during thermomechanical deformations, has profound effects on properties at the macroscopic or component level. Given the respective natures of current detection techniques, a non-destructive, three-dimensional bulk texture detection method for these materials has not yet been developed. This thesis aims to achieve this goal through systematic studies on the relationship between ultrasonic wave velocity and texture. The feasibility of such development is firstly reviewed via the combination of computational and experimental studies on exemplary HCP materials. Numerical results obtained via a representative volume element (RVE) methodology reveal that the wave speed varies progressively and significantly with changing texture, and experimental ultrasound studies combined with EBSD characterisation demonstrate distinguished velocity profiles for samples with different textures. Thus the possibility of the development is demonstrated from these combined results. A novel convolution theorem is then presented, which couples the single crystal wave speed (the kernel function) with polycrystal orientation distribution function to give the resultant polycrystal wave speed function. Firstly developed on HCP and then successfully extended to general anisotropic materials, the theorem expresses the three functions as harmonic expansions thus enabling the calculation of any one of them when the other two are known. Hence, the forward problem of determination of polycrystal wave speed is solved for all crystal systems with verifications on varying textures showing near-perfect representation of the sensitivity of wave speed to texture as well as quantitative predictions of polycrystal wave speed. More importantly, the theorem also presents a solution to the long-standing inverse problem for HCP and cubic materials, with proof of principle established where groups of HCP and cubic textures are recovered solely from polycrystal wave velocities through the theorem and the results show good agreements with the original textures. Therefore the theorem opens up the possibility of developing a powerful technique for bulk texture measurement and wave propagation studies in HCP, cubic materials and beyond.

In obstetrics, the application of computer-based image analysis to provide deeper insight into pathology in early pregnancy is highly desirable but underdeveloped. One such pathology, fetal growth restriction (FGR) is a leading cause of mortality and morbidity in pregnancy. FGR affects approximately 3-10% of pregnancies in the western world leading to increased risk of stillbirth and health problems in later life. Morphometric or functional measurement of the placenta in pregnancy in utero may aid diagnosis of this pathology as the interface between placenta and mother is the site where the pathology manifests itself. Detection of growth restriction is yet to be resolved as poor, unreliable biochemical and image-based biomarkers have made it hard to detect and manage these pregnancies effectively. By the provision and development of tools for quantification of the placenta by three dimensional (3D) ultrasound (US) using image segmentation and mesh pro- cessing, this thesis aims to better facilitate clinical investigation of this major problem in obstetric healthcare. In a first contribution, 3D placental volume measurement using 3D US is used to classify the difference between normal and FGR pregnancies. Volume was estim- ated using the semi-automated random walker (RW) algorithm. The repeatability and reliability of the method was tested between three observers and showed the new method to be equivalent to manual segmentation. In a study of 143 women performed by our clinical partners, significantly smaller placental volume was found in pregnancies defined as small-for-gestational age (SGA). Expanding on volumetry, the utero-placental interface (UPI) is the location where the pathology that leads to FGR occurs. Manual manipulation of the volume is requiredtovisualisetheinterface, soweinvestigatedapplyinga“meshflattening” process to convert the contorted UPI into a disc to provide a standardised way to view the interface between acquistions and subjects. Finally, an existing, two dimensional (2D) Doppler standardisation technique was extended into 3D to provide standardisation of values of Doppler vascularity. This technique was then applied to measure the vascularity of volumes of interest relat- ive to the interface between placenta and mother. This test was then applied clin- ically in 143 women and found that the vascularity of the small-for-gestational age (SGA) pregnancies was significantly smaller than that of the population who produced appropriately sized babies. These three tools each provide augmentation of our understanding of placental health and function in pregnancy. From measuring the gross volume to estimat- ing the blood flow we show the potential clinical application for image analysis performed on 3D power Doppler (PD) ultrasound volumes.

Background: Substantial variation exists between ethnicities in both birth weight and the prevalence of obesity-related non-communicable diseases (OR-NCDs). South Asians, who display a reduced birth weight and increased risk of developing these OR-NCDS, have been the focus of much of the research into the developmental origins of health and disease (DOHaD) paradigm. However, little research utilising ultrasonically derived estimates of fetal growth has been conducted. The use of more direct measures of fetal growth may also enable the identification of relationships between patterns of fetal growth with patterns of postnatal growth, explicitly, whether periods of restricted or rapid growth lead to postnatal catch-up or down, respectively. The known differences in birth weight existing between South Asians and White British infants may also have implications for the assessment of neonatal health in these sub-groups when using a population derived birth weight chart, such as the UK-World Health Organisation (UK-WHO). Customised charts, which adjust for maternal variables including ethnicity, have been recommended for clinical practice, yet evidence for their efficacy is varied. Objectives: The aims of this thesis were to: 1) investigate whether fetal growth patterns differ between Pakistani and White British foetuses and determine whether maternal size and demographic variables mediate any such differences; 2) produce a birth weight chart adjusting for ethnicity and compare this to the UK-WHO and customised birth weight charts to determine which chart better identifies neonates at risk of the adverse delivery and neonatal outcomes associated with small-for-gestational-age (SGA) and large-for-gestational age (LGA); 3) identify whether there is evidence of weight growth tracking between fetal and infant periods and determine whether patterns of fetal growth predict patterns of postnatal growth. Methods: All data come from the Born in Bradford (BiB) birth cohort. Objective 1: Multilevel models and fractional polynomials were employed for the modelling of fetal weight, head circumference (HC) and abdominal circumference (AC) growth. Potential mediators of the effect of being of Pakistani origin were entered into the model and the effect on the ethnicity variable was assessed. Objective 2: Ethnic specific birth weight charts (BiB) were constructed using the LMS method. SGA and LGA were defined as a birth weight <10th and >90th relative to the BiB, the UK-WHO or the customised charts. Sensitivity, specificity, positive & negative predictive values and area-under-the curve were calculated for each of the three charts SGA and LGA cut-offs, to assess the predictive ability of each chart for a range of delivery and neonatal outcomes. Objective 3: Multilevel models were employed for the modelling of fetal and postnatal growth. Fitted values were produced at 20, 30, 40 prenatal weeks & 1, 3, 6, 9, 12, 24 postnatal months in both an internal reference and the sample population. Z scores were calculated and conditional Z scores were generated to account for regression to the mean. Growth tracking was defined as change in Z score ≤ 0.67 & ≥ -0.67. Restricted and rapid fetal growth were defined as a change in Z score in the fetal period of <-0.67 and >0.67, respectively. Catch-down and catch-up growth were defined in the same way, except in the postnatal period. ANOVAs were used to test for differences in size and growth by type of fetal growth. Furthermore, logistic regression and a sensitivity and specificity analysis were employed to examine the predictive ability of the type of fetal growth. Results: Objective 1: Pakistani fetuses were significantly smaller and lighter than White British fetuses, throughout gestation. In terms of weight, Pakistani fetuses were approximately 2.25% lighter at 20 weeks, 4.13% at 30 weeks and 5.94% at 40 weeks. The differences in size for AC and HC between the two groups were not as great, with the AC and HC of Pakistani fetuses being approximately 4.1% and 1.25% smaller, respectively, at 40 weeks. Despite these significant differences in size the pattern of growth for HC and weight was not significantly different between the two groups. There was a trend for Pakistani fetuses to display a greater deceleration of growth in the final trimester (figure 4-12). The biggest mediators of the effect of being of Pakistani origin were maternal height and weight. Objective 2: Classifying infants as SGA or LGA by the BiB, UK-WHO or customised charts had low predictive utility for the outcomes under investigation. Despite the fact that the BiB ethnic specific birth weight reference provided significantly better prediction for more outcomes than both the UK-WHO and customised charts in both White British and Pakistani infants, with the exception of shoulder dystocia, AUROC values for all three charts were all below 0.61. Objective 3: The prevalence of tracking within the same centile band from 20 weeks gestation to 2 years was 10.82%. Infants who experienced restricted fetal growth remained significantly lighter than those who had not, for the duration of infancy. In this group however, there was a pattern of greater growth than expected during infancy. This was opposite to the pattern observed in infants who had experienced rapid fetal growth, who exhibited less growth than expected during infancy. However, the ability of the type of fetal growth to predict the pattern of postnatal growth was minimal, with only rapid fetal growth being significantly associated with increased odds of catch-down growth in infancy. Conclusions: No ethnic difference in the pattern of growth was found in terms of the whole body (weight) or in HC. The trend for reduced growth of the AC in Pakistanis may be a result of a reduced growth of the visceral organs during the third trimester, which may lead to both an altered liver metabolism and impaired renal function in post-natal life. Although being small or large at birth may increase the risk of an adverse neonatal outcome, size alone is not sensitive or specific enough with current detection to be a useful clinical tool. The finding that neither restricted nor rapid fetal growth predicted postnatal catch-up growth may suggest that the timing of canalisation is outside of the fetal period. If infant catch-up and down growth are not associated with periods of restricted or rapid fetal growth, the definitions of these growth patterns may need revising.

Surfactant coated microbubbles are widely used as contrast agents (UCA) in medical ultrasound imaging, due to their high echogenicity and non-linear response to acoustic excitation. Controlling the stability of microbubbles in vivo represents a considerable challenge. Understanding the characteristics of the bubble surface and how they change with production method, composition and environment is key to addressing this problem. The aim of this thesis is to investigate viscosity, bubble dissolution, and acoustic response as functions of their composition, manufacturing method and environment. Bubbles were made using combinations of phospholipid and an emulsifier in different molar ratios. Adding the emulsifier decreased both the size and the surface viscosity of the bubbles and caused changes in the scattered pressure amplitude of bubbles under ultrasound. To increase microbubble stability, solid inorganic nanoparticles were adsorbed on to the microbubble surface. These particles behaved as Pickering stabilisers, and deterred Ostwald ripening. The nanoparticles also enhanced the nonlinear behaviour of bubbles at low acoustic pressures. Three manufacturing methods (sonication, cross-flow and flow focusing) were investigated in order to verify stability differences. Sonication produced bubbles with surface viscosities hundreds of centipoise greater than those produced by microfluidics. Both pressure amplitude and harmonic content for sonicated bubbles were found to be much larger due to a higher liposomal adhesion rate at the surface. Solution temperature and bubble age were also investigated. When the solutions were heated above the phospholipid gelling temperature, microfluidic bubbles showed an increased surface viscosity, due to increased liposome adhesion caused by the increased temperature. Bubble composition, manufacturing method and environment were found to vary the surface characteristics of the microbubbles. Further investigations into the affects of the filling gas, in vitro studies, and low temperature TEM characterisation should be conducted to produce a microbubble with the full range of desired characteristics.

Foetal anomalies found on ultrasound increase the probability of occurrence of chromosomal abnormalities. They cause about one quarter of all abortions and stillbirths and many of inborn defects in newborns. Karyotype analysis is number one method in prenatal diagnosis whereas array CGH is often used as a verification and supplemental method. The aim of this work was to prove that array CGH gives additional chromosomal findings to karyotypes and could substitute conventional karyotyping as a primary examination method in foetuses with ultrasound findings. We examined 45 prenatal samples using both methods. These samples were referred for invasive examination because of abnormal ultrasound findings. Karyotype analyses found two abnormalities in two (4,4 %) patients and array CGH identified aberrations in five (11,1 %) foetuses whereas both anomalies detected by karyotypes were discovered by array CGH too. This means that array CGH identified about 6,7 % more aberrations than karyotype. Our results correspond with scientific articles which refer that array CGH should replace karyotype not only in postnatal examinations but even in prenatal diagnosis. Keywords: chromosomal aberrations, array CGH, karyotype, prenatal diagnosis, ultrasound

Cette étude se place dans le cadre du guidage des thérapies par ultrasons focalisés de haute intensité (HIFU). L’utilisation de l’échographie pour le guidage permet une visualisation temps réel mais un faible contraste. Afin de compenser ce manque de vision du traitement, deux études ont été mises en place. La première sur l’utilité de l’élastographie par compression manuelle en temps réel (23 à 60 images par seconde) a été réalisée et validée par deux protocoles in vivo. L’un a été effectué afin de visualiser des tumeurs VX2 dans le foie chez le lapin de manière extracorporelle et per-opératoire en utilisant une sonde de diagnostique linéaire (12MHz). L’autre a été réalisé sur des porcs avec la même sonde et avec une sonde d'imagerie sectorielle (7,5 MHz) placée au centre du transducteur HIFU. Une comparaison a été menée avec des images IRM des mêmes lésions réalisées après prélèvement de l’organe traité. Dans les deux cas, les élastogrammes assurent une meilleure visualisation des dimensions de la lésion (R=0,70) et un contraste plus important (23dB) en comparaison de l’échographie (R=0,65, contraste=3dB). La dernière partie de ces travaux a permis de démontrer que le signal ultrasonore rétrodiffusé par les tissus du foie change avec la température. Lors d’expériences in vitro et in vivo sur du foie de porc, ce changement de signal se corrèle (R=0,85) avec une hausse de température mesurée par un thermocouple positionné dans la zone focale du transducteur. Cette relation est linéaire positive in vitro et négative in vivo. Cette relation permet de calculer des images de température sur une plage de température allant de 20 à 100°C avec une précision de 5°C. / This study takes place under the guidance of high intensity focused ultrasound therapies (HIFU). The use of ultrasound for guidance allows real time monitoring, but low contrast. To compensate this lack of vision, two studies were set up. The first set up was used to evaluated usefulness of hand-held elastography in real time (23 to 60 frames per second) performed and validated by two in vivo protocols. One was performed to visualize VX2 tumors in the rabbit liver so extracorporeal and intraoperative using a diagnostic linear probe (12MHz). The other was carried out on pigs with the same probe but also with a sectorial imaging probe (7.5 MHz) placed in the center of the HIFU transducer. A comparison was conducted with MRI images of the same lesions performed after removal of the treated organ. In both cases, elastograms provide better visualization of the lesion size (R = 0.70) and higher contrast (23dB) compared to ultrasound (R = 0.65, contrast = 3dB). The last part of this work demonstrated that the ultrasound backscattered signal of the liver tissue changed with the temperature. In experiments on in vitro and in vivo pig livers, this changed of signal is linear and correlated (R = 0.85) with a rise in temperature measured by a thermocouple positioned in the focal zone of the transducer. The relation between backscattered signal and temperature is positive in vitro and negative in vivo. This relationship is linear and used to calculate temperature images with a range of 20 to 100 ° C and an accuracy of 5 ° C.

Les différents processus de dégradation des structures de génie civil induisent une micro, puis macro- fissuration du béton. Celle-ci génère alors une réduction des propriétés mécaniques de l'ouvrage et, à terme, sa perte d'étanchéité. Il est donc nécessaire de fournir des informations quant à la présence et à la taille de fissures pour procéder aux réparations nécessaires et conserver l'intégrité de l'ouvrage. Dans un premier temps, le contrôle du béton ainsi que la morphologie de la fissure réelle sont présentés. La notion de contacts entre ses lèvres est introduite pour définir la problématique de sa caractérisation. La bibliographie montre que les méthodes acoustiques standards ne sont pas adaptées à la caractérisation d'une fissure dans le béton. Deux pistes sont alors identifiées : les ultrasons diffus et l'acoustique non linéaire. Nous présentons dans un second temps la caractérisation de la fissure par analyse du transport de l'énergie suivant une équation de diffusion. Les paramètres associés (diffusivité et dissipation) sont déterminés expérimentalement sur des éprouvettes fissurées sur différentes profondeurs. Nous introduisons et définissons le temps d'arrivée du maximum de l'énergie (ATME) qui s'avère être le paramètre le plus sensible à la partie ouverte d'une fissure. Son évolution au regard des incertitudes de mesure ne permet toutefois pas de caractériser totalement la partie fermée. Une simulation numérique en différences finies est réalisée. Elle met en évidence le rôle des contacts au sein de la partie fermée de la fissure et confirme les observations expérimentales. / The various processes of deterioration of the building structures lead to a micro and macro-cracking of the concrete. Consequently, the mechanical properties of the structure are reduced and, eventually, the building is no longer airtight. It is therefore necessary to supply information regarding the presence and size of cracks to carry out the necessary repairs and keep the integrity of the structure. First, the control of concrete as well as the morphology of the actual crack are presented. The notion of contacts between its lips is introduced to define the problem of its characterization. The bibliography shows that the standard acoustic methods are not adapted for characterizing of a crack in concrete. Two tracks are then identified: the diffuse ultrasound and the nonlinear acoustics. Subsequently, we present the characterization of the crack by analyzing the transport of the energy with a diffusion equation. The associated parameters (diffusivity and dissipation) are experimentally determined on test tubes cracked at different depths. We introduce and define the arrival time of the maximum energy (ATME), which turns out to be the most sensitive parameter to the open part of a crack. Its evolution with regard to the measurement uncertainties does not allow a full characterization of the closed part. A digital modeling in finite differences is performed. It highlights the role of the contacts within the closed part of the crack and confirms the experimental observations. Then, we present the nonlinear acoustics and the associated methods applied to concrete.

Le traitement par ultrasons focalisés (HIFU) associé au contrôle par l’Imagerie de Résonance Magnétique (IRM) est une méthode prometteuse pour les thermothérapies de type non invasive sur patient en respiration libre. Une solution technologique pour l’amélioration du transfert de puissance électrique vers le transducteur ultrason autour d’un système d’adaptation d’impédance ajustable a été réalisée. Un chapitre a été consacré à la caractérisation des transducteurs par la mesure et simulation du champ acoustique spatial. Les deux derniers chapitres, concernent le développement d’outils logiciels autour de l’IRM. Une méthode de caractérisation des paramètres thermiques des tissus chauffés, utile pour une qualité d’asservissement de température optimale, a été développée. Enfin, une étude de faisabilité a été menée sur le couplage des mesures de déplacements rapides par ultrasons avec les mesures robustes fournies par IRM, ceci pour un meilleur suivi du mouvement des organes mobiles. / Treatment with Focused Ultrasound (HIFU) combined with Magnetic Resonance Imaging (MRI) control is a promising method for xxx thermotherapy on patient free breathing. A technological solution for improving the transfer of electrical power to the ultrasonic transducer around a adjustable impedance matching system has been achieved. A chapter was devoted to the characterization of transducers acoustic field by measure and simulation. The last two chapters concern the development of software tools around the MRI. A method to determinate the thermal parameters of tissues heated, useful to compute an optimal temperature control was developed. Finally, a feasibility study has been conducted on the combination of fast ultrasound motion estimation with robust MRI motion estimation, this to improve the quality of the motion tracking.

Resumo: O exame ultra-sonográfico dos testículos é um método não invasivo e rápido, que aliado aos dados de exame clínico, pode conduzir ao diagnóstico precoce de desordens desse órgão, no entanto, a análise da imagem é subjetiva, pois depende do examinador. Sendo assim, instituir valores aos diferentes tons da escala de cinza possibilita a determinação quantitativa do padrão de normalidade para o parênquima testicular. O objetivo do trabalho é avaliar o aspecto ultra-sonográfico e analisar quantitativamente as imagens dos testículos de bovinos jovens da raça Nelore, e estabelecer parâmetros e padrões fisiológicos normais. Foram realizados exames ultrasonográficos dos testículos de 130 bovinos hígidos da raça Nelore, sendo 19 animais da fazenda 1 e 111 animais da fazenda 2. Os animais da fazenda 1 foram avaliados em cinco momentos: aos nove, 11, 13, 15 e 18 meses; ao passo que os da segunda foram avaliados aos nove, 13 e 15 meses. Com o auxílio do software "Echo Image Viewer" (EIV), foram selecionadas regiões de interesse (RI) em cada plano de varredura, assim denominadas: frontal direita (RIFD); frontal esquerda (RIFE); transversal direita (RITD); transversal esquerda (RITE). Automaticamente o software EIV calculou a média da escala de cinzas, a qual variou de 0 a 100%, sendo 0% preto (menor ecogenicidade) e 100% branco (maior ecogenicidade). O teste de Tukey foi empregado para comparar as médias das RI dentro e entre cada momento (p<0,05) utilizando-se o programa estatístico SAS (2001). A ecogenicidade testicular aumentou com o passar da idade nos animais de ambas as fazendas. Touros púberes apresentaram maior ecogenicidade testicular que os impúberes com a mesma idade. A cauda do epidídimo mostrou-se menos ecogênica que o parênquima testicular. A espessura do mediastino testicular, o volume testicular e o perímetro escrotal aumentaram com o passar da idade...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The ultrasononographic examination of testicles is a noninvasive and rapid method that, allied to clinical examination, can lead to an early diagnostic of testicles disorders, however, the image's analysis is subjective, because it depends on the professional. To institute values to different tones of gray scale aloud, then, a quantitative determination of normality's standard to testicular parenchyma. The aim of that study is to evaluate the ultrasonographic's aspect and analyse in a quantitative way the images of young Nelore bovine's testicles, and to establish normal and physiological parameters and standards. Ultrasonographic examinations of 130 healthy Nelore bovines were realized, 19 in farm 1 and 111 in farm 2. The animals of farm 1 were evaluated in five moments: at nine, 11, 13, 15 and 18 months; and the animals of farm 2 were evaluated at nine, 13 and 15 months. With the support of the software "Echo Image Viewer" (EIV), interesting areas (IA) were selected in each plane, forward denominated: right frontal (IArf), left frontal (IAlf), right transversal (IArt), left transversal (IAlt). Automatically the EIV software calculated the gray scale average, on a scale of 0 (black, the less echogenicity) to 100% (white, the most echogenicity). The Tukey test were used to compare the IA's averages in and between each moments (p<0,05) using the SAS statistic program (2001). The testicular echogenicity increased along the ages on both farm's animals. Bulls at puberty showed bigger testicular echogenicity than bulls not at puberty with the same age. The tail of epididymis showed less echogenicity than testicular's parenchyma. The thickness of mediastinum testis, testicular volume and scrotal circumference increased along the ages and positive correlations were found between testicular echogenicity, testicular volume and scrotal circunference. / Orientador: Gilson Helio Toniollo / Coorientador: Júlio Carlos Canola / Coorientadora: Maria Eugênia Zerlotti Mercadante / Banca: Francisco Guilherme Leite / Banca: Sony Dimas Bicudo / Mestre