O câncer de tireoide é um dos mais comuns da região da cabeça e pescoço. Atualmente, o método mais eficaz no diagnóstico de lesões da tireoide é a técnica de biópsia conhecida por punção aspirativa por agulha fina (PAAF) guiada por ultrassom. As imagens de ultrassom são utilizadas como guia para inserção de uma agulha fina até a região da lesão, onde são retirados fragmentos de tecido para análise microscópica. O sucesso dos procedimentos de biópsias está diretamente ligado a experiência do médico desde guiar a agulha à lesão até a preparação das lâminas para análise microscópica. O treinamento médico proporciona, durante a realização dos procedimentos, maior confiança ao médico e maior conforto ao paciente. No entanto o número de pacientes disponíveis, bem como o estágio de graduação do profissional, limitam o número de treinamentos realizados. Com base nessas limitações, esse estudo teve por objetivo o desenvolvimento de um phantom de tireoide permitirá que os treinamentos sejam realizados em qualquer horário e local, minimizando a responsabilidade de alunos e professores. Phantoms para ultrassom, geralmente, são corpos de prova construídos para mimetizar propriedades mecânicas e acústicas dos tecidos biológicos que podem ser utilizados no treinamento de habilidades médicas. Para o desenvolvimento deste modelo, utilizou-se um material a base de hidrocarbonetos de cadeia longa com diferentes concentrações de agentes contraste (pó de vidro, cera de carnaúba, parafina granulada, borracha de silicone). Caracterizou-se amostras de diferentes composições com relação ao módulo elástico, velocidade e atenuação da onda ultrassônica, de modo à atingir valores próximos aos encontrados na literatura para as regiões a serem mimetizadas. Obteve-se valores entre 1385 e 1480 m/s, para velocidade; valores entre 0,4 e 4 dB/cm para atenuação; e uma faixa entre 40 e 750 kPa para o módulo elástico. Ao final da caracterização dos materiais, obteve-se um phantom morfológico de pescoço, contendo a mimetização da tireoide para procedimentos de biópsia de tireoide guiada por ultrassom. / The thyroid cancer is one of the most common of head and neck region. Currently, the most effective method in the diagnosis of thyroid lesions is biopsy technique, known by fine-needle aspiration (FNA) guided by ultrasound. Ultrasound images guides the fine needle insertion into the lesion for sampling and then examined under a microscope. The medical training provides greater confidence to physician and comfort to patient. However, the number of available patients as well as the doctor degree stage limit the number of trainings conducted. Therefore, this study aimed to develop a thyroid phantom to training everywhere at any time, minimizing the students and teachers responsibilities. Ultrasound Phantoms mimics mechanical and acoustic properties of biological tissue and can be used for medical training. To develop the phantom we used a hydrocarbon-based material with different concentrations of contrast agents (glass powder, Carnauba wax, paraffin wax and silicone rubber). We calculated the elastic modulus, velocity and ultrasonic wave attenuation of different mixtures to reach values, as close the literature as possible. Was obtained values from 1385 to 1480 m / s for ultrasound velocity, values from 0.4 to 4 dB/cm for attenuation and a range from 40 to 750 kPa for elastic modulus. This study present an anthropomorphic neck phantom containing the necessary structures for training ultrasound guided biopsy by fine-needle aspiration.

As opposed to current Intraoperative Ultrasound (IOUS) systems and their relatively large probes and limited superficial high frequency imaging, the use of a biopsy needle with an integrated transducer that is capable of minimally invasive and high-resolution ultrasound imaging is proposed. Such a design would overcome the compromise between resolution and penetration depth which is associated with the use of a probe on the skins surface. It is proposed that during interventional procedures, a transducer array positioned at the tip of a biopsy needle could provide real-time image guidance to the clinician with regards to the needle position within the tissue, and aid in the safe navigation of needles towards a particular target such as a tumour in tissues such as the breast, brain or liver, at which point decisions surrounding diagnosis or treatment via in vivo tissue characterisation could be made. With this objective, challenges exist in the manufacturing these miniature scale devices and theirincorporation into needle packages. The reliable realisation of miniature ultrasound transducer arrays on fine-scale piezoelectric composites, and establishing interconnects to these devices which also fit into suitably sized biopsy needles are two such hurdles. In this thesis, the fabrication of miniature 15 MHz ultrasound transducers is presented. The first stage of development involved the production of single element transducers in needles ~2 mm inner diameter, using various piezoelectric materials as the active material. These devices were tested andcharacterised, and the expertise developed during their fabrication was used as the foundation upon which to design a wafer-scale fabrication process for the production of multiple 15 MHz transducer arrays. This process resulted in a 16 element 15 MHz array connected to a flexible printed circuit board and integrated into a breast biopsy needle. Characterisation tests demonstrated functionality of each of the 16 elements, both individually and combined as an array. To explore potential applications for these devices, the single element transducers were tested in fresh and Thiel embalmed cadaveric brain tissue. Plasticine targets were embedded in these brain models and the needle transducers were tested as navigational real-time imaging tools to detect these targets within the brain tissue. The results demonstrated feasibility of such devices to determine the location of the target as the needle devices were advanced or withdrawn from the tissue, showing promise for future devices enabling neurosurgical guidance of interventional tools in the brain. The application of breast imaging was also considered. Firstly, Thiel embalmed cadaveric breasts were assessed as viable breast models for ultrasound imaging. Following this, anatomical features, with diagnostic significance in relation to breast cancer i.e. axillary lymph nodes and milk ducts, were imaged using a range of ultrasound frequencies (6 – 40 MHz). This was carried out to determinepotential design parameters (i.e. operational frequency) of an interventional transducer in a biopsy needle probe which would best visualise these features and aid current breast imaging and diagnosis procedures.

Two issues hindering the clinical application of image-guided transcostal focused ultrasound surgery (FUS) are the organ motion caused by cardiac and respiratory movements and the presence of the ribcage. Intervening ribs absorb and reflect the majority of ultrasound energy excited by an acoustic source, resulting in insufficient energy delivered to the target organs of the liver, kidney, and pancreas. Localized hot spots also exist at the interfaces between the ribs and soft tissue and in highly absorptive regions such as the skin. The aim of this study is to assess the effects of transmitted beam distortion and frequency-dependent rib heating during trans-costal FUS, and to propose potential solutions to reduce the side effects of rib heating and increase ultrasound efficacy. Direct measurements of the transmitted beam propagation were performed on a porcine rib cage phantom, an epoxy rib cage phantom and an acoustic absorber rib cage phantom, in order of their similarities to the human rib cage. Finite element analysis was used to investigate the rib cage geometry, the position of the target tissue relative to the rib cage, and the geometry and operating frequency of the transducer. Of particular importance, frequency-dependent heating at the target and the intervening ribs were estimated along with experimental verification. The ratio of ultrasonic power density at the target and the ribs, the time-varying spatial distribution of temperature, and the ablated focus of each sonication are regarded as key indicators to determine the optimal frequency. Following that, geometric rib-sparing was evaluated by investigating the operation of 2D matrix arrays to optimize focused beam shape and intensity at target. Trans-costal FUS is most useful in treating tumours that are small and near the surface of the abdominal organs, such as the liver, kidney and pancreas. However, for targets deep inside these organs, severe attenuation of acoustic energy occurs, suggesting that pure ultrasound thermal ablation with different heating patterns will have limited effects in improving the treatment efficacy. Results also demonstrate that the optimal ultrasound frequency is around 0.8 MHz for the configurations considered, but that it may shift to higher frequencies with changes in the axial and lateral positions of the tumours. In this work, I aimed to reduce the side effects of rib heating and increase the ultrasound efficacy at the focal point in trans-costal treatment. However, potential advanced techniques need to be explored for further enhanced localized heating in trans-costal FUS.

abstract: Medical ultrasound imaging is widely used today because of it being non-invasive and cost-effective. Flow estimation helps in accurate diagnosis of vascular diseases and adds an important dimension to medical ultrasound imaging. Traditionally flow estimation is done using Doppler-based methods which only estimate velocity in the beam direction. Thus when blood vessels are close to being orthogonal to the beam direction, there are large errors in the estimation results. In this dissertation, a low cost blood flow estimation method that does not have the angle dependency of Doppler-based methods, is presented. First, a velocity estimator based on speckle tracking and synthetic lateral phase is proposed for clutter-free blood flow. Speckle tracking is based on kernel matching and does not have any angle dependency. While velocity estimation in axial dimension is accurate, lateral velocity estimation is challenging due to reduced resolution and lack of phase information. This work presents a two tiered method which estimates the pixel level movement using sum-of-absolute difference, and then estimates the sub-pixel level using synthetic phase information in the lateral dimension. Such a method achieves highly accurate velocity estimation with reduced complexity compared to a cross correlation based method. The average bias of the proposed estimation method is less than 2% for plug flow and less than 7% for parabolic flow. Blood is always accompanied by clutter which originates from vessel wall and surrounding tissues. As magnitude of the blood signal is usually 40-60 dB lower than magnitude of the clutter signal, clutter filtering is necessary before blood flow estimation. Clutter filters utilize the high magnitude and low frequency features of clutter signal to effectively remove them from the compound (blood + clutter) signal. Instead of low complexity FIR filter or high complexity SVD-based filters, here a power/subspace iteration based method is proposed for clutter filtering. Excellent clutter filtering performance is achieved for both slow and fast moving clutters with lower complexity compared to SVD-based filters. For instance, use of the proposed method results in the bias being less than 8% and standard deviation being less than 12% for fast moving clutter when the beam-to-flow-angle is $90^o$. Third, a flow rate estimation method based on kernel power weighting is proposed. As the velocity estimator is a kernel-based method, the estimation accuracy degrades near the vessel boundary. In order to account for kernels that are not fully inside the vessel, fractional weights are given to these kernels based on their signal power. The proposed method achieves excellent flow rate estimation results with less than 8% bias for both slow and fast moving clutters. The performance of the velocity estimator is also evaluated for challenging models. A 2D version of our two-tiered method is able to accurately estimate velocity vectors in a spinning disk as well as in a carotid bifurcation model, both of which are part of the synthetic aperture vector flow imaging (SA-VFI) challenge of 2018. In fact, the proposed method ranked 3rd in the challenge for testing dataset with carotid bifurcation. The flow estimation method is also evaluated for blood flow in vessels with stenosis. Simulation results show that the proposed method is able to estimate the flow rate with less than 9% bias. / Dissertation/Thesis / Doctoral Dissertation Electrical Engineering 2018

Orientador: Wilter Ricardo Russiano Vicente / Coorientador: Frederico Ozanan Barros Monteiro / Banca: Rodrigo del Rio do Valle / Banca: Marcus Antonio Rossi Feliciano / Resumo: Realizou-se o exame ultrassonográfico de macacos-da-noite para avaliar os volumes uterino e ovariano e analisar a interação entre diferentes faixas etárias e número de partos. Foram realizados exames ultrassonográficos da região pélvica, a fim de comparar as dimensões uterinas com o peso, idade (infantil, juvenil, subadulta, adulta jovem e adulta) e número de partos (nulípara, primípara e multípara) e comparar as dimensões ovarianas com o peso e a idade. O volume uterino (VU) foi diretamente proporcional ao número de partos, fator mais importante no crescimento uterino das fêmeas adultas (p < 0,05). O peso e a idade demonstraram uma correlação positiva com o VU (r = 0.5354, r = 0.6489, p < 0.01), respectivamente. O volume dos ovários cresceu proporcionalmente a idade das fêmeas (p < 0,05). A puberdade foi o período de maior crescimento tanto do útero como do ovário / Abstract: We aimed to evaluate the uterine and ovarian volumes of owl monkeys in different age groups with different numbers of live births and to analyze the interaction between both. We performed pelvic ultrasound exams to compare the uterine measurements with weight, age (infant, juvenile, subadult, young adults, and adults) and the number of live births (nulliparous, primiparous, and multiparous) and to compare the ovarian measurements with weight and age. The uterine volume (UV) was directly proportional to the number of parturitions, which was the most important factor in the uterine growth of adult females (P < 0.05). The body weight and age of the animals showed a high positive correlation with UV (r = 0.5354, r = 0.6489, P < 0.01), respectively. The volume of the ovaries grew in proportion to the age of the females (P < 0.05). Puberty was the period of greatest uterine and ovarian growth / Mestre

Coronary artery disease is a leading cause of death in the Western world. Symptoms present only late in the progression of the disease, limiting treatment options; moreover, the inability to biopsy arterial tissue in a living patient makes it difficult to study the pathology effectively. 89 patients were imaged twice at a one year interval using x-ray angiography (the traditional modality for assessment of arterial stenosis) and intravascular ultrasound (IVUS), which yields a detailed image of the structure of the vessel wall. 32 of these 89 patients were made available for analysis in this study. The Volcano Corp.~IVUS acquisition systems include software that provides a \textit{virtual histology} (VH) characterization of plaque composition that provides information otherwise only available by biopsy. Using a geometric reconstruction method described in previous work, a full working model of wall shear stresses (WSS) produced by blood flow and vessel wall composition is created. Using these, the morphologic structural information gleaned from the 3-D reconstruction, and some additional composite indices, combined with demographic information collected at enrollment and serum biomarkers collected from each patient during imaging, a detailed portrait of each patient's disease state is created, with the objective of predicting disease evolution over a 1 year timescale. We have, in the course of this study, accomplished the following 5 aims towards the goal of predicting localized changes in disease state on a 1 year timescale: Aim 1: Develop and validate a method of compensating for rotational motion of the catheter within the vessel and its effect upon the 3-D orientation of the reconstruction. Aim 2: Develop and validate a method of registering the reconstructed vessels that permits identification of a point-to-point correspondence on all quantitative indices. Aim 3: Successfully reconstruct, register, and analyze image sets for each of as many patients as possible for analysis. Aim 4: Identify statistically significant indices in the data suitable for use as features in a classifier. Aim 5: Construct and assess performance of a classification system that can draw useful conclusions about the 1-year progression of the arterial pathology in a patient not used in the training set. Aim 2 was a complete success. Branches were reliably present in the IVUS data in sufficient quantities to facilitate reliable identification of the overlap and the requisite spatial transformation required to map points from one pullback onto another. Aim 1 was much more problematic. While a method was developed which showed promise, the image acquisition protocol did not provide for orientation of the angiograms with an eye towards bifurcation identification. With neither an analytic model, nor reasonable fiducials, the method developed could only be tested on a small subset of the data, limiting both our confidence in its validation, as well as its usability in this study. It is hoped that the method can be refined and used in any subsequent study, given proper planning during the acquisition of the images, and that in turn the spatial reliability of the reconstructions can be improved beyond what is possible today. Regarding aim 3, 32 patients were ultimately processed completely. Aims 4 and 5 were completed successfully. Meaningful correlations were identified in the data, and the results illustrate that while we were by no means able to obtain perfect classification, we were able to handily beat a both a random, and a maximum likelihood classifier.

Articular cartilage, also called shock absorber, is a complex living soft tissue that covers gliding surfaces of joint and enables the joint to withstand weight bearing from human. Since there is no direct blood supply in the articular cartilage, it is generally hard to be repaired itself when it is injured. Although there have been several approaches to the repair of injured articular cartilage, current medical treatment is not able to give patients satisfactory treatment. Ultrasound has been used as one of physical therapy tools. Recently, there have been frequent reports that ultrasound has beneficial effect on the repair of bone fracture and soft tissue healing including articular cartilage. Although there have been appreciation of beneficial effect of ultrasound therapeutically, its mechanism is not fully understood and under investigation. From literature review, several researches tried to find optimal conditions of ultrasound such as intensity, frequency and duration on the repair of articular cartilage and it was reported that more effective ultrasound dose was found. However, different reports have different optimized ultrasound dose. It might be due to the variations of the type of ultrasound wave, intensity, frequency and duration as well as the different condition of experimental samples. Therefore, low intensity pulsed ultrasound (LIPUS) was investigated on the repair of articular cartilage and chondrocyte migration from this study. Also, optimal conditions of LIPUS dose on chondrocyte migration were investigated for the repair of articular cartilage.

Ces travaux de thèse portent sur les récents progrès de l’imagerie fonctionnelle par ultrasons et ses nouvelles applications en ophtalmologie. Dans le cadre d’un projet mêlant physique des ondes, imagerie, neurosciences et ophtalmologie, nous avons appliqué cette technologie à l’imagerie du système visuel et à l’étude préclinique de thérapies le ciblant. Au cours de ce projet, nous avons accompagné nos études précliniques de progrès constants dans notre imagerie.Un dispositif permettant l’imagerie du cerveau en 3 dimensions a été conçu. Cette imagerie a été réalisée en temps réel, ou à une fréquence ultrasonore de 30 MHz grâce au procédé d’entrelacement. Grâce à une connaissance a priori de l’architecture vasculaire cérébrale et de l’effet Doppler, il est possible de réaliser une décomposition spectrale des écoulements sanguins cérébraux selon leurs vitesses et de leurs orientations.Ceci a permis une étude des fonctions visuelles du rat et du primate non-humain. Nous avons imagé la rétine du primate en Doppler de puissance, mais sa forte mobilité en fait un organe délicat à imager en imagerie fonctionnelle. En revanche, nous avons réalisé une imagerie fonctionnelle de la rétine de rat à 30 MHz. Nous avons caractérisé en détail le système visuel cérébral de ce rongeur. Nous avons mis en évidence ses principales structures et redémontré leurs caractéristiques les plus connues, comme leur organisation rétinotopique ou leur différence de temps de réponse neurovasculaire à un stimulus. Des animaux traités par des thérapies de restauration visuelle a été imagée. La première imagerie de primates non-humains anesthésiés puis éveillés et exécutant une tâche comportementale, et la détection de variations de flux sanguins dues à des erreurs uniques ont été réalisées. Enfin, une étude préclinique aiguë et une étude chronique de traitements ayant des effets neurovasculaires ont été menées grâce au suivi du flux sanguin par nos procédés. / This thesis focuses on recent improvements in the functional ultrasound imaging (fUS) technique and their applications in the field of ophthalmology. Within the framework of a synergetic project blending waves physics, medical imaging, neuroscience and ophthalmology, fUS was shown to be capable of imaging and studying the visual system of healthy and diseased animals for the purpose of preclinical studies. To tackle these issues, constant upgrades in the fUS technique had to support the preclinical studies.An experimental set-up was built to image the visual pathway in three dimensions with fUS. Using a new imaging facility, fUS was proven to be feasible in real time and at high ultrasound frequencies such as 30 MHz. Interleaved sampling had to be implemented in that case. Furthermore, the a priori knowledge of the vascular cerebral architecture and the Doppler Effect were exploited to spectrally decompose cerebral blood flux and vessels according to their velocities and orientations.Leveraging these improvements, functional ultrasound imaging of rats and non-human primates was performed. Primate retina was imaged with Power Doppler, but proved to be too mobile to be functionally imaged. However, fUS has been performed on rat retina after 30 MHz fUS imaging had been implemented. The rat visual pathway has then been characterised with fUS. Some of its known features where highlighted such as its retinotopic organisation or the time response differences between some of its structures. The same set-up has been leveraged to map the cerebral activity of animal that underwent visual restauration therapies. These tools were then used to map cerebral activity in anesthetized and awake and behaving monkeys. Unique blood volume variations due to unique mistakes were detected. These tools were finally applied to two preclinical trials on a depressive state of the brain vascular contractility. Blood volume and blood velocity changes were highlighted throughout an acute and a chronical study.

L’encrassement des équipements a lieu dans de nombreux secteurs industriels. Parexemple, la contamination des surfaces de contact avec les aliments, provoquée par un encrassement, entrainent des pertes économiques considérables et augmentent les risques de santé publique. Le nettoyage de l’encrassement est généralement réalisé à l’aide de produits chimiques très polluants. Par conséquent, il est important de développer des dispositifs permettant de surveiller la formation/l’élimination des encrassements sur ces surfaces (sans perturber la production) afin de réduire les risques microbiologiques, les impacts environnementaux et économiques liés aux processus de nettoyage. Dans ce travail, on s’intéresse à la détection du facteur d’encrassement à l’aide d’une méthode ultrasonore non invasive, dite “interférométrie d’ondes de coda”, abrégée en anglais (CWI). Cette technique a été testée pour différents types d’applications (Nettoyage de cire, détection de la formation de biofilm et nettoyage de dépôts protéiques). Les résultats obtenus sont très prometteurs et montrent que la CWI est capable de déceler même un léger changement du facteur d’encrassement. En particulier, l’évolution du coefficient de décorrélation pour chaque application montre une bonne concordance avec l’état d’encrassement réel de la surface. Dans l’ensemble, ces travaux fournissent un ensemble de preuves montrant que la méthode CWI, est applicable au suivi du facteur d’encrassement de dépôts sur des surfaces solides. / Fouling of equipment occurs in many industrial sectors. For example, contamination of surfaces in contact with foodstuff, caused by fouling, causes considerable economic losses and increases public health risks. The cleaning of the fouled surface is generally carried out using highly polluting chemicals. Therefore, it is important to develop devices to monitor the formation / removal of fouling on these surfaces (without disrupting production) in order to reduce the microbiological risks and environmental/economic impacts associated with the cleaning processes. In this work, the detection of fouling factor using a noninvasive ultrasonic method, called "coda wave interferometry", abbreviated in English (CWI), was investigated. This technique has been tested for various types of applications (wax cleaning, biofilm formation detection and protein deposit cleaning). The results obtained are very promising and show that the CWI is able to detect even a slight change in the fouling factor. In particular, the evolution of the decorrelation coefficient for each application shows good agreement with the actual fouling factor. Overall, this work has provided evidence that the CWI method is applicable to the monitoring of fouling factor of solid surfaces.

acase@tulane.edu / Introduction: High-Intensity Focused Ultrasound (HIFU) is the only noninvasive method available today for thermal ablation of tumors. HIFU-induced rapid heating and mechanical disruption of tissue, not only has a direct destructive effect on tumors, but also provides a noninvasive way for targeted release of chemotherapeutic drugs from drug delivery vehicles such as temperature sensitive liposomes (SfTSLs). The objective of this work was to evaluate the synergistic treatment of Sorafenib-loaded TSLs (SfTSLs) and HIFU via in vitro analysis of cell viability and proliferation using an aggressive human liver cancer cell line and corresponding in vivo analysis of tumor growth and survival using a human xenograft mouse model. Materials and Methods: Liposomes were developed using 70% Dipalmitoylphosphatidylcholine, 20% L-a-Phosphatidylcholinehydrogenated Soy, and 10% Cholesterol using thin film hydration method to encapsulate Sorafenib at 10μM. Pellets of Hep3B human liver cancer cells (100 μl, 2.7 million cells/ml) were placed in a 0.2 ml thin-wall PCR tube to mimic dense tumor aggregation. Cell pellets were then inoculated with HIFU alone, SfTSLs, or exposed to a combination of HIFU and SfTSLs. The focused ultrasound signal was generated by a 1.1 MHz transducer with acoustic power ranging from 4.1 W to 12.0 W. Cell viability and proliferation experiments were conducted to measure cancer cell damage at 24, 48, 72, and 96 h post treatment via Annexin V/PI and WST-8 staining. In our in vivo study, 1.0×106 Hep3B cells in Matrigel were injected into left and right flanks of athymic nude mice. Tumors were allowed to grow to 8-10 mm size and then separated into the following treatment groups: HIFU alone, SfTSLs (50 μl) alone, SfTSLs + HIFU, and sham. Tumor sizes were measured by caliper every day and a diagnostic ultrasound system was used pre-treatment, 5 days, 14 days, and prior to sacrificing. Tumors were grouped and processed at 5 days, 14 days, or placed in a survival study to evaluate whether treatment facilitated longer lifespans. Tumor tissues were collected for H&E staining and evaluated by a blinded pathologist post euthanasia. Results and Discussion: Our in vitro data indicate that Hep3B cells exposed to both SfTSLs and HIFU have a significantly lower viability and proliferation rate than untreated cells or the cells treated with only SfTSLs or HIFU. According to our in vivo study, tumor growth in the SfTSLs + HIFU group was reduced as compared to Sham, SfTSLs only, or HIFU only groups. Conclusions: The results of our in vitro and in vivo experiments clearly indicate that chemotherapeutic drug-loaded SfTSLs and HIFU can be an effective therapy for locally aggressive liver cancer. This combination treatment leads to more cellular damage, reduction in tumor growth, and better survival. / 1 / Gray Halliburton