Sabe-se que o aumento na temperatura do tecido tumoral pode aumentar a eficiência de técnicas convencionais de combate ao câncer (radioterapia e quimioterapia). Além disso, a variação de temperatura em tumores pode ser uma forma de tratamento alternativo à cirurgia, feito por meio do fornecimento de calor direcionado às células cancerosas e preservando o tecido sadio. Para maior eficácia e segurança no emprego de técnicas que utilizam fornecimento de calor ao tecido biológico, é necessário o monitoramento da temperatura tecidual para garantir que a morte celular por ablação térmica seja limitada ao tecido alvo, minimizando os danos aos tecidos adjacentes. A imagem fotoacústica é uma técnica baseada no efeito fotoacústico, o qual consiste na absorção de radiação eletromagnética pelo tecido e, devido à expansão termoelástica, na geração de ondas acústicas. A amplitude da onda de pressão gerada pelo efeito fotoacústico possui dependência com a temperatura do meio pelo parâmetro de Grueneisen, que depende das propriedades mecânicas do material. Portanto, mudanças na amplitude do sinal fotoacústico carregam informações a respeito da variação na temperatura do material. Neste trabalho, a dependência da amplitude do sinal fotoacústico com a temperatura foi estudada em um material simulador de tecido biológico (phantom) em condições similares a de tratamentos por hipertermia Nesse caso, imagens fotoacústicas foram adquiridas para cada grau de temperatura em uma faixa de 36 até 41 ºC durante o procedimento de aquecimento por banho térmico. Mudanças na amplitude e fase do sinal fotoacústico foram avaliadas através da aplicação de algoritmos de speckle tracking. Para estimar a variação na amplitude do sinal também foram utilizados e avaliados diferentes métodos de comparação. Os resultados são apresentados por imagens fotoacústicas termais produzidas pela aplicação de um fator de calibração aos mapas de variação relativa da amplitude do sinal em função da temperatura do meio. Finalmente, avaliamos um experimento de hipertemia por ultrassom focalizado de alta intensidade (High Intensity Therapeutic Ultrasound - HITU) em uma amostra de músculo suíno. Nesse caso foram geradas imagens termais fotoacústicas e imagens termais produzidas pela mudança de fase do sinal pulso-eco de ultrassom. Os resultados sugerem uma maneira não invasiva de calcular a distribuição da variação de temperatura do meio que pode ser aplicada para monitoramento durante tratamentos que utilizam o fornecimento de calor ao tecido biológico. / Several studies have shown that elevating the temperature of tumoral tissue improves standard cancer treatments success rate (radiotherapy and chemotherapy). This procedure can also be a therapy to cancer by delivering heat and killing cancer cells while healthy tissues are preserved. For improved efficiency and security in heat applications, it is important to monitor tissue temperature during treatments. Photoacoustic (PA) pressure wave amplitude has a temperature dependence given by the sample mechanical properties (Gruenesein parameter). These changes in photoacoustic signal amplitude carry information about temperature variation in tissue. Therefore, PA has been proposed as an imaging technique to monitor temperature during hyperthermia. In this study, PA images were acquired for temperatures ranging from 36ºC to 41ºC using a tissue-mimicking phantom immersed in a temperature controlled thermal bath. Relative amplitude variation was calculated using speckle tracking algorithms using four different methods to estimate these variations in PA signal amplitude. The results are presented as PA-based thermal images, generated using a calibration factor to the percentage variations in the amplitude maps. Finally, PA-based and ultrasound-based thermal images were acquired during heating by high intensity focused ultrasound (High Intensity Therapeutic Ultrasound - HITU) in a porcine muscle. The results suggest a non-invasive way to monitor temperature during hyperthermia procedures.

Os equipamentos de imagens por ultrassom com varredura eletrônica usam transdutores que não se moldam à superfície a ser examinada, pois são rígidos. Há transdutores com curvaturas fixas para aplicações específicas. Em aplicações médicas, esse não é um problema na maioria dos casos, pois os tecidos do corpo humano tomam a forma da face do transdutor. Isso não ocorre quando há estruturas ósseas próximas às camadas externas de tecidos moles. Nas aplicações industriais as superfícies são sólidas e, portanto, não se ajustam à superfície do transdutor, sendo necessário uma camada variável de acoplamento acústico. A possibilidade de uso de um transdutor flexível exige que sua curvatura seja conhecida para o direcionamento correto do feixe acústico usado na formação de imagens. Assim sendo, um transdutor multielemento flexível apresentaria a vantagem de poder ser acoplado na superfície curva diretamente, tanto em aplicações médicas quanto industriais. Os transdutores flexíveis relatados na literatura científica não são compactos e dispõe de complicados sistemas de sensoriamento usados na determinação de curvaturas, além de demandar por sofisticados sistemas de aquisição e processamento dos sinais. Este trabalho propõe o desenvolvimento de transdutores multielementos flexíveis compactos para serem acoplados diretamente em superfícies curvas de peças mecânicas ou do corpo humano. Neste trabalho os sensores de curvatura responsáveis pela medição da curvatura foram desenvolvidos segundo os princípios básicos de extensômetria e resistência dos materiais para serem embebidos nas camadas do transdutor flexível de ultrassom. No desenvolvimento, foram fabricadas quatro versões de transdutores, com frequências de 1 e 2,25MHz. Todos os materiais usados na fabricação dos protótipos foram especificados segundo suas propriedades mecânicas e acústicas. Os protótipos fabricados foram caracterizados tendo sido medidas a largura de banda de cada elemento do transdutor, o comprimento e a duração dos pulsos, e uma medida da resolução axial. Para o protótipo de 2,25MHz, uma medida estimada da resolução lateral foi feita pela simulação do campo acústico, considerando o transdutor curvado em uma superfície cilíndrica. Para se testar o desempenho dos protótipos, foram realizados diferentes testes de formação de imagem. A versão de transdutor flexível de 1MHz e sem sensor de curvatura foi curvado sobre um cilindro e imerso em um tanque com água para a realização de testes de formação de imagem usado na detecção de objetos e obstáculos. Para as versões de transdutores médicos com sensor de curvatura, construiu-se duas versões de phantom simulando uma interface óssea cortical densa dentro de um tecido mole humano. O phantom usado para testar o protótipo de 2,25MHz foi concebido por uma amostra de tíbia bovina fraturada embebida dentro de um material com propriedades acústicas muito próximas a da água. Os testes de imagem foram realizados com o transdutor de 2,25MHz curvado sobre a superfície cilíndrica do phantom. As imagens de ultrassom das regiões fraturadas do osso foram detectadas, e uma comparação entre as técnicas de varredura setorial e STA usadas na obtenção das imagens foram feitas. Mostrou-se que é possível fabricar, de uma forma simples, transdutores multielementos flexíveis mais compactos e dotados de sensor de curvatura, e sem a necessidade de se usar tecnologias sofisticadas e caras ou de se valer de sistemas complexos de formação e processamento de sinais. As imagens obtidas pelos protótipos mostraram que os protótipos podem ser usados em diferentes aplicações NDT na indústria. Em especial, o protótipo de 2,25MHz mostrou ainda que tem potencial no uso médico para a obtenção de imagens de fraturas em contornos ósseos mais densos. / Ultrasound image equipment with electronic scanning considers that transducers cannot take the shape of the surface to be examined because they are rigid. There are transducers with fixed curvatures for specific applications. In medical applications, this is not a serious problem in most cases, since the face of the transducer can be coupled to the soft tissues of the body. This does not occur when there are bone structures close to the external layers of soft tissue. In industrial applications, the surfaces are solid and therefore do not fit to the transducer surface, where a variable layer of acoustic coupling is necessary. The possibility of using a flexible transducer requires its curvature to be known in order to the correct the direction of the acoustic beam which will be used in imaging applications. Thus, a flexible array transducer would have the advantage of being directly coupled to the curved surface in medical and in industrial applications. Flexible ultrasound transducers reported in the scientific literature are not compact, having complex sensing systems used to determine curvature; furthermore, they require sophisticated signal acquisition and processing systems. The development of flexible compact ultrasound linear array transducers to be coupled directly onto curved surfaces of mechanical parts as well of the human body is proposed here. The bend sensors responsible for measuring the curvature were developed according to the basic principles of strain gauge in extensometry and strength of materials to be embedded in the layers of the flexible ultrasound transducer. During this development, four versions of transducers were manufactured, with frequencies of 1 and 2.25MHz. All the materials used in the prototypes manufacturing were selected based on their mechanical and acoustic properties. The manufactured prototypes were characterized in terms of measured parameters, such as the bandwidth of each transducer element, the length and duration of the pulses, and a measure of axial resolution. For the 2.25MHz prototype, the value of the lateral resolution was estimated by simulating the acoustic field considering the transducer curved over a cylindrical surface. In order to test the transducer prototypes, different ultrasound imaging tests were conducted. The 1MHz flexible transducer version without curvature sensor was bent over a cylinder and immersed in a water tank for performing image formation tests used to detect objects and obstacles. For the medical transducers version with curvature sensor, two versions of phantoms were constructed simulating a dense cortical bone interface located inside the soft human tissue. The phantom applied to test the 2.25 MHz prototype consists of a fractured sample of bovine tibia which was embedded within a material having acoustic properties very close to that of the water. Ultrasound imaging tests were performed with the 2.25MHz transducer curved over the cylindrical surface of the phantom. The regions of the fractured bone were detected in the ultrasound images, and a comparison between the STA and sector scanning techniques used for obtaining the images was made. The study showed that it is possible to manufacture flexible and more compact array transducers provided with curvature sensor, without the need of using sophisticated and expensive technologies or taking advantage of complex formation and signal processing systems. The images obtained by the prototypes showed that they can be employed in different NDT applications in the industry. Particularly, the 2.25MHz prototype also showed its potential for medical imaging fractures in dense bone contours.

The work deals with methods of measuring the parameters of the ultrasonic beam generated by piezoelectric sensors. The theoretical part contains a literature search of methods for the analysis of the ultrasonic beam generated by piezoelectric transducers with dimensions of units of millimeters. The problematics of measurement using piezoelectric or optical fiber hydrophones is investigated in more detail. The scope of the practical part of the work is the design and implementation of measuring equipment that allows spatial analysis of the beam during propagation by a complicated signal path, for automotive level and concentration sensors of the company Vitesco Technologies s.r.o. The system uses a hydrophone method to measure the ultrasonic beam. Due to test measurements, the repeatability of the measured results is confirmed, the results are discussed in the end.

This master's thesis is focused on measurement of the velocity profiles in liquids using ultrasound. The thesis describes two executed measurements both in the channel with free surface, both in the square shaped pipe. In the introductory part this work deals with clarifying the theoretical fundamentals associated with the measurement method UVP such as the Doppler effect, the speed of sound in the medium or the acoustic impedance of the environment. The next part describes the execution of the velocity profile measurement in the channel with free surface described and there is also the description of the results achieved during this measurement. In the last part the thesis deals with the measurement of the velocity profile in the square shaped pipe. There is also the comparison between the measured velocity profiles and the velocity profiles calculated using the analytical formula. In the conclusion there is the evaluation of achieved results.

The topic of this master’s thesis is design of a medical ultrasound diagnostic machine. The thesis focuses on a new perspective on composition and shaping of the ultrasound machine while respecting technical and ergonomic requirements. The goal of this thesis is addition of an aesthetic value and incorporation of new technologies so the product is able to compete on the current market.

An adequate vascular perfusion status is essential not only to maintain life, but to ensure the proper physiology of the different systems that form the animal’s body. Due to its role in the transport of oxygen and nutrients toward, and the removal of cellular waste products away from the body’s tissues, the circulatory system is responsible for the maintenance of body homeostasis. Production related functions in farm animals are not an exception, and directly depend on sufficient vascular physiology. In the past, the study of blood flow in large domestic species was restricted to highly invasive techniques. However, even when such techniques are the foundation for the actual understanding of vascular dynamics in these animals, their limited feasibility and potential impact over the normal vascular physiology represent significant limitations to these approaches. Recently, the development and application of non-invasive technologies (i.e., Doppler and B- mode ultrasound) to the area of animal sciences has provided the potential for the study of vascular dynamics while, the negative implications aforementioned are avoided. In our studies, these technologies were applied to assess the role of the circulatory system on different production related variables such as: temperament, reproduction, and milk production in the bovine. A tendency toward differences in jugular blood flow was associated with the temperament in beef calves in this study. Also, a significant increase in vasodilation in the uterine arteries of beef cows was found to be associated with a numerically higher reproductive efficiency (i.e., pregnancy rates). Moreover, an increase in blood flow towards the mammary gland in dairy cows was associated with administration of bovine somatotropin. In conclusion, B- mode and Doppler ultrasound resulted in tools able to reflect the essential role of an adequate vascular perfusion in the normal physiology and productive performance in the bovine. However, in real farm scenarios the feasibility of these techniques in large domestic species is limited. Therefore, further specialization of this instrument to the conditions existent in such farm scenarios are recommended to improve its feasibility and to significantly accelerate the rate of knowledge acquisition in this area.

Ultrasound-mediated drug delivery has been proposed as a safe and non-invasive method to achieve localized drug release. Drug-loaded microbubbles are injected in the vascular system and ultrasound waves are then used to localize and burst the microbubbles at a specific targeted area. The relatively large size of microbubbles however limits both their lifetime and their reach in the human body. Phase-change liquid droplets can extend the use of ultrasound contrast agents for localized drug delivery. Their smaller size provides several advantages. The droplets can reach smaller capillaries, such as those in tumors vasculature. Their lifetime is also considerably prolonged. Through the phenomenon of Acoustic Droplet Vaporization (ADV), triggered by ultrasound stimulation, the liquid-filled droplets experience a phase change and are converted into gas-filled microbubbles. The newly created microbubbles can then be disrupted by further stimulation and release their drug load in the tumor tissue. In this project, a protocol to image and burst perfluoropentane-based micro-sized droplets using a single transducer is developed using the Verasonics Ultrasound System. The pulse sequences are developed to allow close monitoring of the drug delivery by capturing a series of images before and after the vaporization or destruction of the droplets. The droplets response was assessed for different pulse voltages and durations. Mean pixel value was calculated for the regions of interest, using the images captured before and after delivery of the ultrasound pulse. Vaporization of the droplets can be achieved with low voltage (10V), whereas high voltage (50V) triggers their destruction. Combined with high voltage, pulse duration affects the rate at which droplets can be destructed.

The harmonic generation due to the nonlinear behavior of Ultrasound Contrast Agents (UCAs) must be exploited for improved efficiency when imaging vascular targets in the neighborhood of highly echogenic tissue. One may even further improve the efficiency by focusing on the subharmonic generation of the UCAs, which is an even more exclusive property than the generation of higher harmonics, for improved Contrast-to-Tissue ratio (CTR). The aim of this work was first, the design of a set-up for nonlinear imaging of Poly-Vinyl Alcohol (PVA) based UCAs on The Verasonics Research System with special focus on nondestructive Subharmonic Imaging. The second part of the work addressed the evaluation of the subharmonic response provided by the agents in the developed setup. Six different imaging techniques were developed. These were Fundamental B-mode imaging (FB), Pulse Inversion imaging (PI), and a Contrast Pulse Sequence based on three pulses (CPS3), with and without a focus on the subharmonic component by the implementation of a Linear Bandpass Filter (LBF). Experiments were performed on a tissue mimicking flow phantom and the performance of the agents for each technique was determined in terms of CTR and CNR. The PVA agents provided a backscattering enhancement of the order of 23 dB through FB imaging. However, the performance of the FB technique was unsatisfactory in terms of CTR. The CPS3 sequence performed best of the six techniques with an improvement of 14 dB and 13 dB in CTR and CNR, respectively, compared with the FB technique. Combining the LBF around the subharmonic component with the multi-pulse techniques of PI and CPS3 resulted in a degraded CTR performance due to significant amount of signals from tissue around the subharmonic component and insufficient subharmonic detection from the PVA agents.

No description available.

Tendon injuries are prevalent, debilitating and difficult to treat. Common interventions such as anti-inflammatory medication, growth factor injections and surgery are associated with short-term efficacy and long rehabilitation periods. Tendons possess an incomplete healing response which is reparative (scar-mediated) rather than regenerative, resulting in a 'healed' tissue that is mechanically inferior to the native tendon. While it is widely accepted that mechanical-loading based treatments offer long-term symptomatic resolution and improved functionality, the exact mechanisms of action of such mechanotransduction-based healing cascades remain unclear. Nevertheless, there is significant motivation for the development of non-invasive and efficient rehabilitative treatments that mechanically stimulate the injured tendons to achieve functional healing responses. Focused Ultrasound (FUS) methods are an attractive treatment option as they are non-invasive, utilize higher intensities for shorter durations and are targeted to a very specific treatment volume, hence inducing significant bio-effects in the tissue without affecting surrounding structures. Herein, we present a body of work that includes the development of FUS pulsing to precisely target murine Achilles tendons and emphasize distinct bioeffects (thermal-dominant and mechanical-dominant). We investigated the feasibility of applying FUS pulsing to murine Achilles tendons ex vivo and in vivo and demonstrated that FUS can be safely applied without any deleterious effects in the tendons and surrounding tissues. The animals showed no symptoms of distress after multi-session treatments. Overall, results suggest that tendon material properties are not adversely altered by FUS pulsing. Histological analyses showed mild matrix disorganization, suggesting the need for slight modifications in the ultrasound pulsing parameters and treatment durations. When applied to injured tendons, mechanical dominant schemes seemed to drive larger improvements in material properties compared to thermal-dominant pulsing, confirming our original hypothesis that mechanical stimulation may play a bigger role in tendon healing compared to purely thermal-dominant stimulation. Additionally, feasibility of histotripsy ablation in murine Achilles tendons was successfully investigated ex vivo and in vivo and experimentation to further optimize these methods are ongoing. Such (non-thermal) ablative paradigms will be extremely useful when conservative treatment options are unavailable and debridement of scar tissue is warranted to interrupt the degenerative process and stimulate healing. Finally, a pilot investigation into FUS-induced strains was performed to guide our parameter selection process and deliver controlled strains to achieve healing responses (similar to current clinical rehabilitation protocols). We were able confirm that strains between 1% and 6% (or higher) can be induced by manipulating ultrasound treatment parameters. Overall, or results reiterate the potential of FUS in eliciting the desired bioeffects and thus achieve healing in tendons and provide a snapshot of the expected effects of using such pulsing methods to treat tendon injuries. / Doctor of Philosophy / Tendons are tissues that connect muscles to bones, and are unfortunately prone to injuries. Such injuries are prevalent and difficult to treat. Effective treatment options remain limited, as common methods such as surgery, anti-inflammatory medications and corticosteroid injections do not provide long-term relief. One of the few treatments that has been proven to provide symptomatic relief and improved the functionality of chronically (over a long period of time) injured tendons is physical therapy. However, researchers are still investigating the reasons for this successful healing response. Some limitations of physical therapy are long rehabilitation and recovery periods, and the need for patient compliance (i.e., performing painful exercises while already being under significant pain). In this research, we explore the use of a non-invasive modality known as ultrasound to treat tendon injuries. Ultrasound is commonly thought of as a diagnostic tool, i.e., to detect injuries in musculoskeletal medicine. It, however, is also an attractive therapeutic (treatment) modality, as sound waves can be concentrated in the required area of interest which results in different types of effects in the chosen tissue, such as heating. A huge advantage is that ultrasound is non-invasive, painless, and safe, as the energy is only applied to the chosen volume of interest and surrounding structures are unaffected. To examine the utility of therapeutic ultrasound in treating tendon injuries, we used a mouse model that has been previously used in our lab, and designed different types of ultrasound treatments that elicit two main types of effects in the tissue, namely, thermal, or heating effects and mechanical, or physical therapy-like effects. Prior to applying these treatments, we measured how much heating is produced in mouse Achilles tendons via these treatments, to establish safety. Once we identified safe thermal and mechanical treatment sets, we treated mouse Achilles tendons ex vivo, i.e., after euthanasia. We tested the mechanical properties of the treated tendons and determined that treatments do not alter the mechanical properties of tendons, which is encouraging, given that we do not want treatments to interfere with the properties of native tendons. We also examined the influence of treatments on structure of Achilles tendons after treatments and deducted that the structure was not damaged due to treatments. We followed up these studies with treatments conducted in live mice, which received four treatment sessions in one week. These studies were conducted to further determine the safety and tolerance to these procedures and also examine the healing effects of treatments in injured Achilles tendons. Results suggest that focused ultrasound treatments are safe and tolerable to mice and seem to elicit improvements in tendon properties. In other studies, we also examined a different ultrasound method named histotripsy, as a non-invasive alternative to dry needling (which is another methodology used to treat tendon injuries) and scar debridement (removal of scar tissue to stimulate a new healing response). This research establishes that therapeutic ultrasound is a novel, non-invasive alternative with good potential to treat tendon injuries. Future studies will investigate the effects of ultrasound treatments over longer durations and also aim to clarify the exact type and magnitude of physical therapy-like forces that are produced by ultrasound treatments. This understanding will enhance our treatment design process to be able to mimic clinical treatments that are known to be effective.