Low intensity and low frequency ultrasound has been shown to modulate ion channel currents, membrane capacitive currents, and as a result, neuronal activity. Ultrasound has been used as a non-invasive way to modulate neuronal activity in vivo using mice as well as human subjects. Ultrasound with acoustic frequency as low as 0.35 MHz can be focussed on a region as small as 2 mm with reversible effects and no increase in temperature. In this study, two ultrasound transducers with different resonant frequency have been used to excite neuronal cultures. The resulting changes in the network properties such as synchronised network burst frequency, density, clustering and path length have been analysed. The study shows that ultrasound stimulation at acoustic frequency 450 kHz (ISPPA =11.3 mW/cm2) significantly modulates the above mentioned parameters and causes deviations from small world network properties of the control network.

Palatalization refers to a type of coarticulation in which the place of articulation of some sound is closer to the palate than otherwise expected, very often triggered by adjacent palatal segments. It has been known as one of the most dynamic phonological phenomena in phonetic and phonological research, but the articulatory nature of palatalization still merits further investigation. This dissertation investigates the articulatory patterns of palatalization in Korean, English, and Scottish Gaelic (Gàidhlig), all of which are typologically distinct from one another and exhibit both language-universal and language-specific palatalization processes. The main question asked in this dissertation is which articulatory properties of palatalization are universal across languages, and specific to languages or to individuals. Three production experiments using ultrasound imaging technology were conducted to capture tongue gestures of speakers from three different language groups. The results from 30 speakers in the three language groups show that both phonemic and phonetic plain vs. palatalized differences manifest gesturally. Furthermore, the results show that there is a significant amount of articulatory variability across languages and speakers, yielding no clear universal "palatal" gesture, but some articulatory strategies seem to be shared by speakers from different languages. The theoretical and empirical implications of the findings are discussed.

Cardiovascular diseases (CVDs) constitute a leading cause of death, including premature death, in the developed world. The early diagnosis and treatment of CVDs is therefore of great importance. Modern imaging modalities enable the quantification and analysis of the cardiovascular system and provide researchers and clinicians with valuable tools for the diagnosis and treatment of CVDs. In particular, echocardiography offers a number of advantages, compared to other imaging modalities, making it a prevalent tool for assessing cardiac morphology and function. However, cardiac ultrasound images can suffer from a range of artifacts reducing their image quality and diagnostic value. As a result, there is great interest in the development of processing techniques that address such limitations. This thesis introduces and quantitatively evaluates four methods that enhance clinical cardiac ultrasound data by utilising information which until now has been predominantly disregarded. All methods introduced in this thesis utilise multiple partially uncorrelated instances of a cardiac cycle in order to acquire the information required to suppress or enhance certain image features. No filtering out of information is performed at any stage throughout the processing. This constitutes the main differentiation to previous data enhancement approaches which tend to filter out information based on some static or adaptive selection criteria. The first two image enhancement methods utilise spatial averaging of partially uncorrelated data acquired through a single acoustic window. More precisely, Temporal Compounding enhances cardiac ultrasound data by averaging partially uncorrelated instances of the imaged structure acquired over a number of consecutive cardiac cycles. An extension to the notion of spatial compounding of cardiac ultrasound data is 3D-to-2D Compounding, which presents a novel image enhancement method by acquiring and compounding spatially adjacent (along the elevation plane), partially uncorrelated, 2D slices of the heart extracted as a thin angular sub-sector of a volumetric pyramid scan. Data enhancement introduced by both approaches includes the substantial suppression of tissue speckle and cavity noise. Furthermore, by averaging decorrelated instances of the same cardiac structure, both compounding methods can enhance tissue structures, which are masked out by high levels of noise and shadowing, increasing their corresponding tissue/cavity detectability. The third novel data enhancement approach, referred as Dynamic Histogram Based Intensity Mapping (DHBIM), investigates the temporal variations within image histograms of consecutive frames in order to (i) identify any unutilised/underutilised intensity levels and (ii) derive the tissue/cavity intensity threshold within the processed frame sequence. Piecewise intensity mapping is then used to enhance cardiac ultrasound data. DHBIM introduces cavity noise suppression, enhancement of tissue speckle information as well as considerable increase in tissue/cavity contrast and detectability. A data acquisition and analysis protocol for integrating the dynamic intensity mapping along with spatial compounding methods is also investigated. The linear integration of DHBIM and Temporal Compounding forms the fourth and final implemented method, which is also quantitatively assessed. By taking advantage of the benefits and compensating for the limitations of each individual method, the integrated method suppresses cavity noise and tissue speckle while enhancing tissue/cavity contrast as well as the delineation of cardiac tissue boundaries even when heavily corrupted by cardiac ultrasound artifacts. Finally, a novel protocol for the quantitative assessment of the effect of each data enhancement method on image quality and diagnostic value is employed. This enables the quantitative evaluation of each method as well as the comparison between individual methods using clinical data from 32 patients. Image quality is assessed using a range of quantitative measures such as signal-to-noise ratio, tissue/cavity contrast and detectability index. Diagnostic value is assessed through variations in the repeatability level of routine clinical measurements performed on patient cardiac ultrasound scans by two experienced echocardiographers. Commonly used clinical measures such as the wall thickness of the Interventricular Septum (IVS) and the Left Ventricle Posterior Wall (LVPW) as well as the cavity diameter of the Left Ventricle (LVID) and Left Atrium (LAD) are employed for assessing diagnostic value.

Ultrasound contrast agents have the ability to provide locally increased echogenicity, improving the sensitivity and specificity of images. Due to the unique interaction of microbubbles with the imaging ultrasound field, contrast ultrasonography offers both improved diagnostic techniques, and the potential therapeutic uses of gene and drug delivery through the use of targeted agents. By enhancing the contrast at the tissue-blood interface, an improved image of the structure of organs can be achieved, which is useful in many areas of medical ultrasound imaging. Monitoring the flow of contrast agent in the blood stream also offers information on the degree of blood perfusion into an organ or microvasculature. Present knowledge of the interaction of microbubbles with ultrasound is far from complete. The full potential of contrast agents in improving diagnostic and therapeutic techniques has therefore not yet been achieved. The nonlinear and dynamic properties of microbubble response offer potentially large improvements in contrast to tissue ratio, through intelligent pulse sequence design and/or improved signal processing. Due to various drawbacks of populations studies, only by studying the response from single microbubbles can the interaction be fully understood. The variations of microbubble size and shell parameters within a typical sample of contrast agent dictate that a large number of single scatterer data are necessary to obtain information on the variability of microbubble response, which is not possible with current optical systems. This thesis aims to be a contribution to the understanding of contrast behaviour in response to medical imaging ultrasound pulses. A fully characterized microacoustic system, employing a wide-band piezoelectric transducer from a commercial ultrasound imaging system, is introduced, which enables the measurement of single scattering events. Single microbubble signals from two commercially available contrast agents, Definity R and biSphereTM, have been measured experimentally in response to a range of clinically relevant imaging parameters. The data has been analyzed, together with the results from appropriate theoretical models, in order to gain physical insight into the evolution and dynamics of microbubble signals. A theoretical model for the lipid shelled agent Definity has been developed, and the predicted response from a real sample of single microbubbles investigated. Various characteristics of resonant scatter have been identified, and used to distinguish resonant scatter in experimental acoustic single bubble data for the first time. A clear distinction between the populations of resonant and off-resonant scatter has been observed for a range of incident frequencies and acoustic pressures. Results from consecutive imaging pulses have been used to gain understanding of how initial size, shell material and encapsulated gas may effect the lifetime of a microbubble signal. The response to a basic pulse sequence is also investigated, and an alternative processing method which takes advantage of observed behaviour is presented. Improved understanding of the contrast-ultrasound interaction will provide the basis for improved signal processing tools for contrast enhanced imaging, with potential benefits to both diagnostic techniques and microbubble manufacture.

Recent advances in medical imaging have greatly improved the success of cardiovascular and intracardiac interventions. This research aims to improve capacitive micromachined ultrasonic transducers (CMUT) based imaging catheters for intravascular ultrasound (IVUS) and intra-cardiac echocardiography (ICE) for 3-D volumetric imaging through integration of high-k thin film material into the CMUT fabrication and array design. CMUT-on-CMOS integration has been recently achieved and initial imaging of ex-vivo samples with adequate dynamic range for IVUS at 20MHz has been demonstrated; however, for imaging in the heart, higher sensitivities are needed for imaging up to 4-5 cm depth at 20MHz and deeper at 10MHz. Consequently, one research goal is to design 10-20MHz CMUT arrays using integrated circuit (IC) compatible micro fabrication techniques and optimizing transducer performance through high-k dielectrics such as hafnium oxide (HfO2). This thin film material is electrically characterized for its dielectric properties and thermal mechanical stress is measured. Experiments on test CMUTs show a +6dB improvement in receive (Rx) sensitivity, and +6dB improvement in transmit sensitivity in (Pa/V) as compared to a CMUT using silicon nitride isolation (SixNy) layer. CMUT-on-CMOS with HfO2 insulation is successfully integrated and images of a pig-artery was successfully obtained with a 40dB dynamic range for 1x1cm2 planes. Experimental demonstration of side looking capability of single chip CMUT on CMOS system based FL dual ring arrays supported by large signal and FEA simulations was presented. The experimental results which are in agreement with simulations show promising results for the viability of using FL-IVUS CMUT-on-CMOS device with dual mode side-forward looking imaging. Three dimensional images were obtained by the CMUT-on-CMOS array for both a front facing wire and 4 wires that are placed perpendicular to the array surface and ~4 mm away laterally. For a novel array design, a dual gap, dual frequency 2D array was designed, fabricated and verified against the large signal model for CMUTs. Three different CMUT element geometries (2 receive, 1 transmit) were designed to achieve ~20MHz and ~40MHz bands respectively in pulse-echo mode. A system level framework for designing CMUT arrays was described that include effects from imaging design requirements, acoustical cross-talk, bandwidths, signal-to-noise (SNR) optimization and considerations from IC limitations for pulse voltage. Electrical impedance measurements and hydrophone measurements comparisons between design and experiment show differences due to inaccuracies in using SixNy homogenous material in simulation compared to fabricated thin-film stacks (HfO2-AlSi-SixNy). It is concluded that for “thin” membranes the effect of stiffness and mass of HfO2 and AlSi (top electrode) cannot be ignored in the simulation. Also, it is understood that aspect ratio (width to height) <10 will have up to 15% error for center frequency predicted in air when the thin-plate approximation is used for modelling the bending stiffness of the CMUT membrane.

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Spine needle injections are widely applied to alleviate pain and to remove nerve sensation through anesthesia. Current treatment is performed either blindly having no image guidance or using fluoroscopy or computed tomography (CT). Both CT and fluoroscopy guidance expose patients to ionizing radiation. Alternatively, ultrasound (US) guidance for spine needle procedures is becoming more prevalent since US is a non-ionizing and more accessible image modality. An inherent challenge to US imaging of the spine is the acoustic shadows created by the bony structures of the vertebra limiting visibility. It is challenging to use US as the sole imaging modality for intraoperative guidance of spine needle injections. However, it is possible to enhance the anatomical information through a preoperative diagnostic CT. To achieve this, image registration between the CT and the US images is proposed in this thesis. Image registration integrates the anatomical information from the CT with the US images. The aligned CT augments anatomical visualization for the clinician during spinal interventions. To align the preoperative CT and intraoperative US, a novel registration pipeline is presented that involves automatic global and multi-vertebrae registration. The registration pipeline is composed of two distinct phases: preoperative and intraoperative. Preoperatively, artificial spring points are selected between adjacent vertebrae. Intraoperatively, the lumbar spine is first aligned between the CT and US followed by a multi-vertebrae registration. The artificial springs are used to constrain the movement of the individually transformed vertebrae to ensure the optimal alignment is a pose of the lumbar spine that is physically possible. Validation of the algorithm is performed on five clinical patient datasets. A protocol for US data collection was created to eliminate variability in the quality of acquired US images. The registration pipeline was able to register the datasets from initial misalignments of up to 25 mm with a mean TRE of 1.17 mm. From these results, it is evident that the proposed registration pipeline offers a robust registration between clinical CT and US data. / Thesis (Master, Computing) -- Queen's University, 2013-08-19 12:50:54.521

The growing worldwide use of clinician-performed ultrasound (CPU) marks a dramatic change in bedside medicine and patient care. With steadily improving portability, accessibility and technology, ultrasound use continues to grow amongst many medical specialties. Likewise, the application of CPU in emergency medicine is increasing. Emergency Medicine (EM) is a medical specialty “based on the knowledge and skills required for the prevention, diagnosis and management of acute and urgent aspects of illness and injury…” (International Federation for Emergency Medicine, 1991). Increasingly, emergency physicians are using emergency department ultrasound (ED U/S) to enhance their assessment of critically-ill patients (American College of Emergency Physicians, 2008). The purpose of this study was to evaluate and describe those aspects of ultrasound simulation (during HFS) that contribute to the development of critical care ED U/S skills. Secondly, it was of interest to assess how a novel ultrasound simulator (edus2) compared to video playback on a laptop in terms of the above-mentioned aspects. The population of interest included both EM trainees and faculty. This investigation was a randomized, prospective, crossover study with two intervention treatments for all participants. In Phase I, EM trainees and faculty from London, UK, were invited to participate in one of four day-long critical-care HFS sessions during which they participated in four critical-care scenarios. Faculty were involved in assisting with session debriefing and feedback. All participants completed two cases with each intervention. In Phase II, faculty in Saskatoon, SK, Canada, were invited to review video recordings of the sessions from Phase I and evaluate the educational merits of the two ED U/S simulation interventions. iii This study produced both quantitative and qualitative data. As this study looked at two interventions and how they could contribute to the development of ED U/S skills, pre- and postintervention changes were analysed for statistically significant differences between them. T-test analyses were used for comparisons. Effect sizes (Cohen’s d) were calculated where statistically significant findings were observed. Qualitative data was assessed through emergent thematic analysis and triangulation. The findings of the study support the integration of ED U/S simulation into HFS. Integration was found to be of value to both trainees and faculty by allowing trainees to demonstrate knowledge of indications as well as correct image interpretation and general integration of ED U/S into critical care (p<0.05). Trainees described an increased motivation to develop their ED U/S skills as well as greater desire to use ED U/S in everyday practice. Furthermore, the edus2 was identified as being the preferred training intervention. The edus2 met functional fidelity through its real time and hands-on applicability. Faculty preferred the edus2 as it allowed for better assessment of trainee skills that then influenced session debriefing and formative feedback. Faculty in Phase II found the edus2 intervention sufficient in offering basic insights into trainee ED U/S skills and mastery (p<0.05). Implications of the study include support for the use of ultrasound simulation during HFS for the development of critical care ED U/S skills amongst EM trainees. Further study on the effects of such hybrid simulation on clinical performance is warranted.