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Focused ultrasound therapy can be enhanced with microbubbles by thermal and cavitation effects. However, localization of treatment becomes difficult as bioeffects can occur outside of the target region. Spatial control of gas bubbles can be achieved with acoustic vaporization of perfluorocarbon droplets. This study was undertaken to determine the acoustic parameters for bubble production by droplet vaporization and how it depends on the acoustic conditions and droplet physical parameters. Droplets of varying sizes were sonicated in vitro with a focused ultrasound transducer and varying frequency and exposure. Simultaneous measurements of the vaporization and inertial cavitation thresholds were performed. The results show that droplets cannot be vaporized at low frequency without inertial cavitation occurring. However, the vaporization threshold decreased with increasing frequency, exposure and droplet size. In summary, we have demonstrated that droplet vaporization is feasible for clinically-relevant sized droplets and acoustic exposures.

abstract: Neurostimulation methods currently include deep brain stimulation (DBS), optogenetic, transcranial direct-current stimulation (tDCS), and transcranial magnetic stimulation (TMS). TMS and tDCS are noninvasive techniques whereas DBS and optogenetic require surgical implantation of electrodes or light emitting devices. All approaches, except for optogenetic, have been implemented in clinical settings because they have demonstrated therapeutic utility and clinical efficacy for neurological and psychiatric disorders. When applied for therapeutic applications, these techniques suffer from limitations that hinder the progression of its intended use to treat compromised brain function. DBS requires an invasive surgical procedure that surfaces complications from infection, longevity of electrical components, and immune responses to foreign materials. Both TMS and tDCS circumvent the problems seen with DBS as they are noninvasive procedures, but they fail to produce the spatial resolution required to target specific brain structures. Realizing these restrictions, we sought out to use ultrasound as a neurostimulation modality. Ultrasound is capable of achieving greater resolution than TMS and tDCS, as we have demonstrated a ~2mm lateral resolution, which can be delivered noninvasively. These characteristics place ultrasound superior to current neurostimulation methods. For these reasons, this dissertation provides a developed protocol to use transcranial pulsed ultrasound (TPU) as a neurostimulation technique. These investigations implement electrophysiological, optophysiological, immunohistological, and behavioral methods to elucidate the effects of ultrasound on the central nervous system and raise questions about the functional consequences. Intriguingly, we showed that TPU was also capable of stimulating intact sub-cortical circuits in the anesthetized mouse. These data reveal that TPU can evoke synchronous oscillations in the hippocampus in addition to increasing expression of brain-derived neurotrophic factor (BDNF). Considering these observations, and the ability to noninvasively stimulate neuronal activity on a mesoscale resolution, reveals a potential avenue to be effective in clinical settings where current brain stimulation techniques have shown to be beneficial. Thus, the results explained by this dissertation help to pronounce the significance for these protocols to gain translational recognition. / Dissertation/Thesis / Ph.D. Biology 2011

Ultrasound is one of the primary technologies used for clinical purposes. Ultrasound systems have favorable real-time capabilities, are fast and relatively inexpensive, portable and non-invasive. Recent interest in using ultrasound imaging for tongue motion has various applications in linguistic study, speech therapy as well as in foreign language education, where visual-feedback of tongue motion complements conventional audio feedback. Ultrasound images are known to be difficult to recognize. The anatomical structure in them, the rapidity of tongue movements, also missing segments in some frames and the limited frame rate of ultrasound systems have made automatic tongue contour extraction and tracking very challenging and especially hard for real-time applications. Traditional image processing-based approaches have many practical limitations in terms of automation, speed, and accuracy. Recent progress in deep convolutional neural networks has been successfully exploited in a variety of computer vision problems such as detection, classification, and segmentation. In the past few years, deep belief networks for tongue segmentation and convolutional neural networks for the classification of tongue motion have been proposed. However, none of these claim fully-automatic or real-time performance. U-Net is one of the most popular deep learning algorithms for image segmentation, and it is composed of several convolutions and deconvolution layers. In this thesis, we proposed a fully automatic system to extract tongue dorsum from ultrasound videos in real-time using a simplified version of U-Net, which we call sU-Net. Two databases from different machines were collected, and different training schemes were applied for testing the learning capability of the model. Our experiment on ultrasound video data demonstrates that the proposed method is very competitive compared with other methods in terms of performance and accuracy.

Diante das vantagens do uso do ultra-som na confecção de cavidades retrógradas, o presente estudo avaliou pontas lisas, diamantadas e despolidas quanto ao tempo usado para confecção das cavidades, presença de sujidade e infiltração do corante rodamina a 0,2%. Após os tratamentos endodônticos e apicectomias dos trinta e quatro dentes uniradiculares estudados, estes foram divididos em três grupos de 10; de acordo com a ponta usada para o retropreparo. A confecção das cavidades retrógradas consistiu de duas fases: fase 1 (a ponta de ultra-som deveria atingir 3mm de profundidade, não visualização de sujidade a “olho nu”, preparo com características de classe I), e fase 2 (uso da ponta de ultra -som correspondente a cada grupo por mais 40 segundos). Ao final de cada fase, os espécimes foram avaliados sob microscópio óptico com aumento de 20X e fotografados. Quatro examinadores analisaram a presença de sujidade nas superfícies retropreparadas. O tempo gasto para a confecção da fase 1 foi anotado. Em seguida, todos os espécimes submeteram-se a retrobturação com MTA. Passado período de 72 horas, foram imersos em solução de rodamina a 0,2% e clivados após 24 horas. A hemi-parte que continha maior infiltração de cada espécime, foi a considerada. Os resultados mostraram que as pontas despolidas necessitam de menos tempo para confecção de cavidades retrógradas. Após mais 40 segundos de preparo (fase 2), houve diminuição na quantidade de sujidade, em todos os grupos, não havendo diferença estatística significante entre os grupos. Em relação a infiltração do corante rodamina a 0,2%, os resultados mostraram não haver diferença estatística significante, quando da comparação entre os preparos confeccionados por pontas lisas, diamantadas e despolidas e retrobturados pelo MTA. Concluímos, portanto, que o tipo de ponta de ultra-som influencia no tempo de preparo, apesar de não exercer influência na infiltração do MTA. Vale ressaltar que a presença de sujidade é intensamente minimizada quando da complementação dos preparos por mais 40 segundos. / Given the advantages of the use of ultrasound in the preparation of retrograde cavities, the present study evaluated the smooth, diamond -coated and use of no polished tips regarding the time required for the preparation of cavities, the presence of dirt and the penetration of the 0,2% rhodamine dye solution. After the apicectomy and endodontic treatment of the thirty-four single -rooted teeth studied, we divided them into 3 groups of 10 according to the tip used in the rootend preparation. Four roots were used as positive and negative controls. The preparation of the retrograde cavities consisted of two phases: phase 1 (the ultrasound tip should reach 3mm of depth; dirt should not be spotted by the naked eye; preparation with class I characteristics), and phase 2 (use of the ultrasound tip corresponding to each group for more than 40 seconds). At the end of each phase, the specimens were evaluated under an optical microscope that enhanced them 20X, and were then photographed. Four examiners analyzed the presence of dirt in the root-end preparation surfaces. The time spent in phase 1 was recorded. All the specimens were then root-end filling with MTA. After 72 hours, they were submerged in a 0,2% rhodamine solution and cleaved after 24 hours. We then analyzed the hemi-part that contained the highest penetration. The results showed that the no polished tips require shorter time in the preparation of retrograde cavities. After over 40 seconds of preparation (phase 2), there was a reduction in the amount of dirt in all the groups studied, with no signify cant differences between the groups. As regards the penetration of the rhodamine dye at 0,2%, the results did not show statistically significant differences as regards preparations with smooth, diamondcoated and no polished tips, and root-end filling with MTA. Therefore , we concluded that the type of ultrasound tip influences the preparation time, even though it has no influence on the penetration of MTA. It is important to stress that the presence of dirt is highly minimized when the preparation is complemented by 40 more seconds.

Objective: In this study, I have directly tracked the progression of angiogenesis for three different types of breast cancer cell lines; MDA-MB-231, MCF-7, and MDA-MB-468. Each of these cell lines is known to overexpress different receptors, which may affect a tumor’s growth rate and perhaps its ability to undergo angiogenesis. Here, I measure and compare the growth, extent, and time of onset for angiogenesis. Methods: I used SCID mice to profile each of the different breast cancer cell lines. The growth rate of each tumor, along with its blood vessel development, was monitored and imaged using lipid-coated microbubbles and contrast-enhanced ultrasound (CEUS). A Vevo 2100 pre-clinical ultrasound machine was used for the imaging experiments. To track development of angiogenesis, mice were injected with perfluorobutane gas microbubbles of 1-2 microns diameter. Bubble perfusion into the tumor is an indicator of the presence of blood vessel formation. A custom image analysis program was developed in Matlab™ to eliminate breathing artifacts and track microbubble motion based on their high temporal frequency signature ("flicker"). Results: My experiments demonstrated that, although different cell lines grow at different rates, microbubbles begin to penetrate the tumor when it reaches approximately a size of approximately 3 mm in diameter. Therefore, the onset of angiogenesis occurred at different times (MCF-7 occurring first at around 9 days, MDA-MB-468 occuring at 12 days post inoculation, and MDA-MB-231 occurring at 17 days post tumor cell inoculation). Matlab™ analysis demonstrates consistent angiogenic behavior among the three cell lines. Conclusion: For all cell lines, angiogenesis started when the volume of the tumor was approximately 21.76 mm³, consistent with previous studies. As angiogenesis progressed, there was a drop in tumor blood flow. This can be explained by the sudden influx of oxygen when angiogenesis first begins. This momentarily inhibits new blood vessel formation while the tumor continues to steadily grow. After this sudden drop, tumor vascularization resumes a steady increase.

The main goal of the project was to develop new experimental techniques to further investigate the phase diagram of the ferromagnetic superconductor UGe2 at high pressures. Of particular interest is the metamagnetic transition (FM1-FM2) which is thought to play the key role in the unconventional superconductivity in UGe2. The project attempted to detect experimentally the critical ferromagnetic fluctuations associated with the FM1-FM2 transition. The development of the experimental equipment constitutes a substantial part of the project and includes: (1) a 2-axis Rotation Stage for High Pressures, (2) an Ultrasonic Sapphire Anvil Cell and (3) a High Pressure Pulse Echo Setup. (1) allows transport measurement on single crystal samples with simultaneous two-axis rotation at temperatures down to 2 K, magnetic fields up to 9T and pressures up to 5GPa to be made. (2) employs Resonant Ultrasound Spectroscopy on a sample in the anvil type cell with an optical access at cryogenic temperatures. (3) uses the Pulse Echo Technique inside a cylinder type cell allowing for ultrasonic measurements on samples with a well-defined orientation. The design, technical challenges and tests results are presented and discussed. The existing techniques, used in the project, included Inelastic Neutron Scattering. A single crystal of UGe2 was studied at 12 kbar with a large volume two-layered piston-cylinder cell. No critical fluctuations were detected at Tx associated with the FM1-FM2 transition. Instead, a small inelastic signal below this transition temperature was observed at the threshold of the instrument sensitivity. The fluctuations at TC associated with the paramagnetic-to-ferromagnetic transition (PM-FM) were detected and the energy scale of these fluctuations was found to have decreased, as compared to the ambient pressure case, in proportion to the resistivity - a result supporting recent theory. The elastic constant c11 of a single crystal of UGe2 was measured as a function of temperature using (3) at ambient pressure as well as pressures up to 11 kbar. The elastic constant exhibits clear features associated with the two transitions, PM-FM and FM1-FM2. The temperature dependence of the elastic constant at ambient pressure was modelled with two main contributions (Schottky-like and Wiess-like) to the magnetic heat capacity coming from the two energy scales, Tx and TC, as well as two corresponding Gruneisen parameters, Ωx and ΩC. The values of Gruneisen parameters obtained from the data fitting were in good agreement with the values determined from the slope of the phase transition lines on the phase diagram. The temperature dependence of the elastic constant at high pressures was modelled according to the two-component system with coupled moments. The behaviour of the fitting parameters (including the Ωx and ΩT ) was consistent with the phase diagram of UGe2 and captured important features of c11 temperature evolution. The way forward would be to continue the measurements of c11 at higher pressures but also to repeat the measurements at different ultrasonic frequencies in order to obtain the temperature dependence of the ultrasonic attenuation which will provide more insight on the FM1-FM2 transition.

Anaerobic digestion is a useful method for stabilizing and reducing the waste activated sludges (WAS) produced from biological secondary treatment. Pretreatments can make anaerobic digestion more efficient. However, the study of anaerobic digestion and pretreatments is limited to a focus in treating conventional WAS. Therefore, WAS from three non-conventional municipal wastewater treatment systems, a rotating biological contactor (RBC), a lagoon, and a moving bed bioreactor (MBBR), were digested anaerobically to determine the sludges’ biogas potentials compared to a conventional WAS. All three WAS had lower biogas potential normalized per volatile solids than conventional sludge by 46% + 6 (MBBR), 63% + 6 (RBC), and 77% + 7 (lagoon). The four sludges were pretreated with ultrasonic energies of 800 - 6550 kJ/kg TS to illustrate impact of sludge type on biogas production, solubilization, and digestion kinetics. All four sludge types responded uniquely to the same levels of sonication energies. The greatest increase in biogas production over the control of pretreated sludge did not coincide consistently with greater sonication energy but occurred within a solubilization range of 2.9 – 7.4% degree of disintegration (DD) and are as follows: 5% + 3 biogas increase for conventional sludge, 12% + 9 for lagoon, 15% + 2 for MBBR and 20% + 2 for RBC. The yield of biogas production related to soluble COD decreases with increased sonication energy. Hence it is likely that sonication produces refractory COD or causes inhibition in biogas production. The effect of sonication on digestion kinetics was inconclusive with the application of Modified Gompertz, Reaction Curve, and First Order models to biogas production. Diauxic growth patterns of biogas production of sonicated conventional waste demonstrates that the active time of digestion can be decreased through the conversion of less preferential substrates into existing, preferential substrates.

Location tracking on mobile devices like smartphones has already begun to revolutionize personal navigation. Unfortunately, these services perform poorly indoors when GPS signals are no longer available. Highly accurate indoor location tracking would enhance a wide variety of applications including: building navigation (malls, factories, airports), augmented reality, location-aware pervasive computing, targeted advertising, social networking, participatory sensing and could even support next generation beam forming MIMO wireless networks. Current indoor localization systems for smartphones often use RF signal strength from WiFi access points or Bluetooth Low Energy (BLE) beacons to fingerprint indoor locations. Such systems are sensitive to environmental changes and obstructions, require extensive training procedures and are limited in both absolute as well as semantic localization accuracy. We propose using audio signals in the ultrasound spectrum, just above the human hearing range, to provide ranging and localization for many off-the-shelf mobile devices that are equipped with microphones. Ultrasonic ranging provides several advantages over RF-based ranging and fingerprinting approaches, which make it attractive for indoor localization. A relatively low propagation speed and carrier frequency allow for precise propagation time measurements in software using commodity hardware. Acoustic signals also have a low penetration depth, which confines them to target areas for accurate semantic localization. In this dissertation we address several challenges related to acoustic localization, including system scalability, ranging and localization accuracy, energy efficiency, robustness to noise, elimination of human perceivable audio artifacts, efficient use of limited acoustic bandwidth and rapid deployment strategies.

Le but de cette étude était d'évaluer la faisabilité et la reproductilité de l'élastographie ShearWave par voie transabdominale d’organes fœtaux et du placenta chez les babouines gestantes.Matériels et méthodes: Les échographies fœtales de tous les babouines gestantes ont été réalisées prospectivement pendant 9 mois dans un seul centre de recherche sur les primates. La visualisation des organes foetaux cibles (foie, poumons proximal et distal, substance blanche du cerveau et matière grise périventriculaire) et du placenta a été initialement effectuée en utilisant l'échographie 2D pour le repérage des organes, puis le mode élastographique a été activé. Pour chaque organe, trois mesures ont été effectuées par deux opérateurs. On a calculé les coefficients de corrélation intra-classe (CCI) intra-observateur et inter-observateur.Résultats: Au cours de la période d'étude (03/2013 - 12/2013), 21 babouines gestantes ont été inclus correspondant à 21 foetus. Une à trois échographies ont été réalisées pour chaque fœtus. Les mesures ont été réalisables par les deux opérateurs dans tous les cas. Le CCI intra-observateur et inter-observateur était de 0,654 - IC 95% (0,606 à 0,699) et 0,645 - IC 95% (0,553 à 0,721), respectivement.Conclusion: L’élastographie ShearWave par voie transabdominale des organes fœtaux et du placenta peut être réalisée chez les babouines gestantes. La reproductibilité intra-observateur et inter-observateur est correcte mais varie selon les organes visés. / The purpose of this study was to assess the feasibility and reproducibility of transabdominal ShearWaveTM elastography of fetal organs and placenta in pregnant baboons.Materials and methods: Fetal ultrasounds of all pregnant baboons in a single primate research center were performed prospectively during 9 months. The visualization of fetal targeted organs (liver, proximal and distal lungs, brain white substance and periventricular gray substance) was initially performed using 2D ultrasound, and then elastography mode was activated. For each organ, three measurements were carried out by two operators. Intra-observer and inter-observer intra-class correlation coefficients (ICC) were calculated.Results: During the study period (03/2013–12/2013), 21 pregnant baboons (21 fetuses) were included. One to three ultrasound scans were performed for each fetus. The measurements were feasible by the two operators in all cases. The intra-observer and inter-observer ICC were 0.654, 95% CI (0.606 to 0.699) and 0.645, 95% CI (0.553 to 0.721) respectively.Conclusion: Transabdominal ShearWaveTM Elastography of fetal organs can be achieved in pregnant baboons. The intra-observer and inter-observer reproducibility is correct but vary according to the targeted organs.ves: The purpose of this study was to assess the feasibility and reproducibility of transabdominal ShearWaveTM elastography of fetal organs and placenta in pregnant baboons.