A prototype acoustic streaming pump for microfluidic applications was developed. A novel integration scheme was devised based on the acoustic reflector concept. Numerical simulations were conducted to predict the flow patterns around the transducer. Ultrasound transducers using P(VDF-TrFE) as the piezoelectric element were fabricated using lithography-based microfabrication technology. Silicon channels were fabricated using anisotropic etching. A heat-press bonding technique was adopted to bond the transducers with the silicon chips using CYTOP fluoropolymer as the adhesive. The piezoelectric transducers were characterized to have a resonance frequency of 82 MHz. Micro-PIV experiments were performed in the near and far-fields of the ultrasonic transducer/pump. The near field experiments showed complex flow patterns that could enhance mixing. Estimates of the pumping pressure were obtained using transient flow velocities in the far-field. Conservative estimates indicate the total back pressure the micropump can pump against is 39 Pa. Future research directions were suggested.

Cleft lip and/or palate is a craniofacial condition that can lead to complex speech disorders. In particular, the auditory-perceptual speech assessments of individuals with cleft palate can be difficult because cleft-type compensatory articulations may be outside of English phonology. Therefore, it is desirable to supplement auditory-perceptual assessments with instrumental measurements. In the first study, thirteen participants with cleft-type compensatory articulations completed ultrasound speech exams. The stimuli were repeated VCV combinations (target consonants: [t], [k], [s], [sh], [n], [ng]; vowel contexts: [a], [i], [u]). Ultrasound imaging confirmed auditory-perceptual impressions and revealed covert articulatory movements. In the second study, six participants were assessed after a course of speech therapy. Outcomes were recorded on a severity metric with categories describing auditory-perceptual and motor aspects of speech errors. The severity metric quantified the incremental changes in both dimensions. Based on the research presented, further investigations of cleft palate speech using ultrasound are warranted.

Diagnostic ultrasound is a non-invasive image modality commonly used to diagnose multiple diseases. Sonographers and physicians have to devote a substantial amount of time learning how the combination of the various parameters of the ultrasound system affects the resulting ultrasound information among its different modalities. The primary objective of this thesis is to create a mechanistic ultrasound simulation method that could achieve near real-time performance to teach and train sonographers and physicians. A major bottleneck for achieving real-time performance with available tools was the transducer field simulation method that uses the impulse response technique. To address this problem a new simulation approach was developed. This project was realized in a three-phase approach, specifically to simulate spectral Doppler. In first place, it was shown that is possible to mechanistically simulate the sample volume power distribution using a novel method based on an array of point sources to represent the transducer geometry. Secondly, by comparison with the Field II results, it was demonstrated that the time-domain signal could be closely reproduced using point sources. Finally, by treating the array of point sources as point receivers, the received signal was compared with the results from Field II, and again, good agreement was achieved. Simulation results were compared against the standard simulation method for a number of examples involving steady and pulsatile flow, for which the spectrograms were compared against Field II. Also presented are preliminary results obtained using the point source approach to simulate B-mode images. As well, methods are described for generating Doppler spectrograms from the results of computation fluid dynamics velocity fields obtained in realistic arterial geometrical models. It is pointed out that the successful simulation of the time domain signal opens the possibility for real-time simulation of other ultrasound modes.

Capacitive micromachined ultrasonic transducers (CMUTs) have proven themselves to be excellent candidates for medical ultrasonic imaging applications. The use of semiconductor fabrication techniques facilitates the fabrication of high quality arrays of uniform cells and elements, broad acoustic bandwidth, the potential to integrate the transducers with the necessary electronics, and the opportunity to exploit the benefits of batch fabrication. In this thesis, the design, fabrication and testing of one- and two-dimensional CMUT arrays using a novel wafer bonding process whereby the membrane and the insulation layer are both silicon nitride is reported. A user-grown insulating membrane layer avoids the need for expensive SOI wafers, permits optimization of the electrode size, and allows more freedom in selecting the membrane thickness, while also enjoying the benefits of wafer bonding fabrication. Using a row-column addressing scheme for an NxN two-dimensional array permits three-dimensional imaging with a large reduction in the complexity of the array when compared to a conventional 2D array with connections to all N2 elements. Only 2N connections are required and the image acquisition rate has the potential to be greatly increased. A simplification of the device at the imaging end will facilitate the integration of a three-dimensional imaging CMUT array into either an endoscope or catheter which is the ultimate purpose of this research project. To date, many sizes of transducers which operate at different frequencies have been successfully fabricated. Initial characterization in terms of resonant frequency and, transmission and reception in immersion has been performed on most of the device types. Extensive characterization has been performed with a linear 32 element array transducer and a 32x32 element row-column transducer. Two- and three-dimensional phased array imaging has been demonstrated.

Gas Metal Arc welding (GMAW) is one of the primary techniques used to join structural components together. The major obstacle precluding full closed-loop control of GMAW has been the lack of robust techniques using non-destructive and non-contact sensors capable of operating in high temperature and harsh environments typical of GMAW processes. This research uses laser generated ultrasound and electromagnetic acoustic transducer (EMAT) to receive ultrasound. Previous research has focused on ultrasonic shear wave time of flight (TOF) techniques to determine weld penetration depth, a key measure of weld quality. The objective of this research was to use a new technique, frequency modulation of a laser phased array (FMLPA), to determine weld penetration depth. Theoretical background of the FMLPA was developed. An analytical model of the FMLPA was derived and validated through experimentation. The FMLPA was experimentally validated. However, both the FMLPA and shear wave TOF techniques have proven to be impractical for real-time control. These techniques are impractical because the required ultrasonic waves are difficult to acquire due to attenuation and interference from other waves. A new type of wave called the RGLS wave was discovered during the course of this research. The RGLS wave was used to create a new RGLS TOF method for measuring weld penetration depth. The RGLS TOF method for measuring weld penetration depth has proven to be highly accurate, precise, and repeatable. The RGLS TOF method for measuring weld penetration depth has been demonstrated to work both off-line after welding and real-time during welding. Although the FMLPA and shear wave TOF technique was proven to be impractical, the RGLS TOF method has met the ultimate goal of this research area. Other new methods such as the RGSL, RGLL, and RGSS TOF methods related to the RGLS TOF method was also developed. The RGLS TOF method is suited for non-destructive and non-contact sensing. It will help future researchers achieve closed-loop control and automation of the GMAW process, which will help to improve quality and efficiency of welding, and also reduce waste and cost of welding parts together.

Abstract The objective of this thesis is to study the biological effects of larvae of Aedes albopictus induced by ultrasound exposure. Ultrasound is widely used in medical and biological techniques, most of them are cell killing or tumor eliminating by high-intensity ultrasound. In order to analyse the influences of ultrasound biological effects in vivo, the larvae of mosquito, in this research, were exposed to continuous-wave ultrasound. Some preliminary observations were made with 0-day larvae. The oscillation of the trachea in larvae in response to the ultrasound radiation is simulated using Miller¡¦s cylindrical-bubble activation theory. Dimensions of tubes in the respiratory system of larvae were measured by microscope. The resonant frequency of the tracheae were calculated, and its range is about 0.6¡ã1.5 MHz. It was observed that the tracheae in 0-day larvae were ruptured by ultrasound exposure, and the larvae were dead in the duration of growth, some fourth instar larvae failed to mature into pupae. The maximum mosquito larvae mortality was with 1 MHz irradiation, and it¡¦s in good agreement with the resonant frequency calculated in this paper.

I experimentally studied ultrasound-modulated optical tomography, which holds the promise for biomedical diagnosis. I measured the degree of polarization of laser speckles generated by scattered light transmitted through turbid media, investigated three signal-detection schemes for extracting the intensity of the ultrasound-modulated light, carried out experiments to image thick biological-tissue samples, and studied two techniques providing resolution in the cross-sections containing the ultrasonic axis. The study of degree of polarization presented results important for the understanding of polarization phenomena in turbid media. I explored an optical-filtering based signal detection scheme, improved the parallel-lock-in speckle detection scheme and proposed a speckle-contrast detection scheme. With the speckle-contrast detection scheme, I successfully obtained images of biological-tissue samples up to 50 mm thick. Further I studied frequency-swept ultrasound-modulated optical tomography for sub-millimeter resolution imaging, and developed ultrasound-modulated optical computed tomography that was based on a back-projection image reconstruction method and obtained clear images of biological-tissue samples.

Hepatocellular carcinoma (HCC) is one of deadliest cancers worldwide and ranking the third among all cancer-related mortalities. Current effective therapeutic approaches for HCC include surgical resection and trans-arterial embolization (TAE). Chemotherapy remains largely ineffective, and most popular used agents are epirubicin, doxorubicin, cisplatin and 5-FU. Besides, these chemotherapic drugs had potential serious side-effects such as low blood count, hair loss, vomiting, and they rarely present good anti-HCC effect in clinical practice. Our previous studies found that epirubicin injection attenuated the tumor burden of orthotopic Novikoff hepatoma, but caused serious side effects to hosts including reduction in spleen weight, white count, and body weight and high GOT level. Therefore, we aimed to evaluate possible alternative treatment such as COX-2 inhibitor for HCC. Celecoxib is a highly selective COX-2 inhibitor and less toxic than the traditional non-selective NSAIDs. Celecoxib showed relatively low cytotoxicity in Novikoff N1-S1 hepatoma cells and Clone 9 normal hepatocytes with an IC50 of up to 100 microM. Expression analysis revealed that COX-2 expression is very low in N1-S1 cells at protein and mRNA levels. Thus, N1-S1 is a kind of hepatoma cell line with low COX-II level. Interestingly, celecoxib upregulated PTEN expression and decreased AKT phosphorylation in vitro by COX-2 independent pathway, and then oral administration of celecoxib (30 mg/kg) for 7 days showed tendency of tumor suppression of Novikoff hepatoma in rats revealed by ultrasound and computed tomography (CT) scan. Histological analysis revealed that CD31-positive neo-vascularization¡BKi-67-positive cell-proliferation and FOXP3-positive regulatory T cells were found to reduce in celecoxib-treated rats, and then TUNEL-positive apoptotic cells were found to increase in celecoxib-treated rats. Besides, celecoxib-treated rats exhibited no significant side effect. Therefore, oral celecoxib may be a suitable chose of adjuvant therapy in combination with epirubicin or other chemotherapeutic agents for the treatment of HCC.

Medical ultrasound imaging is ubiquitous in clinics due to its safety, low cost, portability, and imaging depth. The development of technologies to assist ultrasound in the diagnosis of diseases thus have a potentially broad clinical impact. More recently, photoacoustics has emerged as a complementary, high contrast modality for imaging optical absorption. Injectable dyes and nanoparticles locally amplify ultrasound and photoacoustic signal, helping to identify disease markers and track its progression. We have constructed a dual ultrasound and photoacoustic contrast agent that can be activated using an external optical trigger. In response to pulsed laser irradiation, the particle undergoes a liquid to gas phase change, or vaporization, which emits a strong acoustic wave and results in an echogenic microbubble, simultaneously enhancing contrast for both modalities. We designed and developed several iterations of particles, altering parameters to optimize biocompatibility, cost, and image contrast enhancement, and we then characterized key traits of the particles. Next, we imaged the contrast agents in phantom, ex vivo, and in vivo models to validate the image enhancement, developing image process algorithms to maximize image quality. These optically triggered contrast agents are a valuable tool for minimally invasive, highly specific, early identification of cancer. / text

Η παρούσα διατριβή πραγματεύεται τον σχεδιασμό, την ανάπτυξη και υλοποίηση νέων μεθόδων επεξεργασίας εικόνας βασισμένες στον μετασχηματισμό μικροκυματιδίων (Wavelet Transform) με σκοπό την αφαίρεση θορύβου και την τμηματοποίηση των όζων καθώς και ανάλυσης εικόνας με σκοπό την αυτόματη ταξινόμηση των όζων σε όζους υψηλού και χαμηλού κινδύνου. / The aim of the present thesis was the design and implementation of new image processing and analysis methods in ultrasound thyroid images. The research procedure comprised two main concepts towards optimization of thyroid ultrasonography. The design and implementation of wavelet-based image processing methods towards speckle suppression and thyroid nodule segmentation and image analysis methods in order to evaluate the thyroid nodules malignancy risk factor.