<p>In the United States, heart failure is a leading cause of hospitalization. The medical industry places great emphasis on diagnosing heart disease through cardiac metrics like ejection fraction. Left ventricular ejection fraction is a commonly used diagnostic indicator for heart efficiency and is measured with echocardiography through different volume calculation techniques. However, ejection fraction results can drastically vary from one examiner to another. Generally cardiologists still give ejection fraction measurements a plus or minus 10 percent error range. </p><p>A program developed at Duke called 4DViz is robust enough for users to process 3D ultrasound data. 4DViz allows examiners to determine heart chamber volumes by constructing a surface model over an imaged heart chamber with many mouse click inputs. Through 4DViz programming, a viable approach for calculating ejection fraction is attempted in this thesis. Using feature tracking, surface drawing, and voxel filling, the new approach aims to reduce examiner input and improve ejection fraction consistency. Water filled balloons were used to calibrate the algorithm's parameters. In testing, several volunteers were asked to use the 4DViz. Their results are compared to volume measurements where user input was standard. The results show promise and may remove some of the inconsistency behind ejection fraction measurements.</p> / Thesis

Increased demand for smaller electronics is driving the electronic packaging industry to develop smaller, more efficient component level packages. Surface mounted components, such as flip chips, ball grid arrays (BGAs), and chip-scale packages (CSPs), are being developed for use in high-volume production. All of these technologies use solder bumps to attach the active silicon to the substrate, and traditional nondestructive methods such as machine vision, acoustic microscopy or x-ray inspection cannot easily find solder bump defects. Therefore, a system, consisting of an Nd:YAG laser that delivers pulses of infrared energy to the surface of the chip, a laser interferometer to record surface vibrations, and a high-speed data acquisition system to record the signals, was developed. The pulsed laser generates ultrasound on the chips surface, exciting the whole chip into a vibration motion, and the interferometer measures the vibration displacement of the chips surface at several points. Changes in the quality of the device or its attachment to the board produce changes in the free vibration response. Characterization of the differences between good devices and devices with defects, both in time domain and frequency domain, is performed using signal analysis. The system has inspected flip chips and chip scale packages for missing and misaligned solder balls, but to characterize the resolution of the system for open solder joints, a study of the vibration modes excited by the laser source in a flip chip was performed on specimens with intentionally created defects. Experimental measurements of excited modes were compared with a modal analysis model created in ANSYS, and defects were detected as small changes in the mode shape on the surface of the chips. Current inspection methods have also been inadequate for inspecting multi-layer ceramic capacitors (MLCCs). Flex cracks, caused by manufacturing processes, often cause the capacitors to fail in-service. Samples that have been cracked intentionally were compared with reference samples to determine the feasibility of using this technique to monitor the condition of MLCCs on an assembly line. Currently, there is no on-line inspection method for controlling this problem, but this technique was able to differentiate between good and damaged capacitors.

The aim of this study was to characterize the interaction between a pulsed ultrasonic wave and a paper forming screen for potential development of a smart paper forming sensor to measure velocity profile of the forming jet as it impinges on the wire. To achieve this goal, a Signal-Processing DOP 2000 pulsed ultrasonic Doppler velocimeter was used to generate a pulsed ultrasonic signal. The signal was transmitted and received using four different ultrasonic transducers: a 2 MHz 10 mm, 4 MHz 5 mm, 4MHz 8 mm focused, and 8 MHz 5 mm. The ultrasonic signals were then analyzed in order to determine the ultrasonic beam echo amplitude and shape. These tests were performed with and without various paper forming screens placed between the ultrasonic transducer and an ultrasonic signal target. Two different paper forming screens were utilized to study the interaction of the ultrasonic beam with the forming screens. The tests showed that the ultrasonic signal passing through the forming screens is greatly attenuated causing a sharp decrease in echo amplitude. To overcome the attenuation of the signal, a much higher amplification of the signal was used causing an increase in the saturation region around the forming screen. This increased the minimum distance that a target had to be away from the forming screen. The closest distance from the plastic sphere to the screen over the widest range of transducer-screen-distances that produced detectable echoes was achieved with the 4 MHz 5 mm transducer. The tests showed for both screens that there is more variation in beam width when the screen is moved laterally than when it is not moved at all. They also show that even though the pores in the forming screen are very small, they seem to have a great effect on the beam width measurements of the ultrasonic transducer.

The inability to transport molecules efficiently and easily into cells and across tissues is one of the major limitations of developing drug delivery systems. A novel approach to overcoming this problem could be the use of low-frequency ultrasound to make cell membranes and tissues more permeable. Previous studies show that normally impermeant molecules can be transported into cells exposed to ultrasound; however, the mechanism by which this occurs is not well understood. Our hypothesis is that low frequency ultrasound can reversibly disrupt membrane structure, thus allowing diffusion-driven intracellular delivery of molecules through a breach in the cell membrane. The effects of ultrasound are not limited to uptake of molecules; there can also be significant loss of cell viability after sonication. Therefore, the focus of this work is to determine the mechanisms by which molecular uptake and cell death occur from ultrasound exposure. The long-term goal of this work is to increase the number of viable cells that experience uptake by controlling the effects that cause cell death. Our data have show that large molecules (r ≤ 28 nm) can be taken into cells after exposure to 24 kHz (10% duty cycle for 2 s of exposure time at 0.1 pulse length over a range of pressures) ultrasound and that uptake of these molecules can occur even after sonication ended. In experiments developed to isolate the mechanism(s) of uptake, DU145 prostate cancer cells depleted of ATP energy and intracellular calcium showed no uptake of calcein, a small fluorescent molecule (MW = 623 Da), nor did sonicated lipid bilayers (red blood cell ghosts), suggesting that uptake is calcium mediated and requires active mechanisms in viable cells. Multiple types of microscopy, including electron and laser scanning confocal, showed evidence of large plasma membrane disruptions which support the hypothesis that transport of molecules into cells occurs through repairing wounds. Microscopy studies also indicated that much if the sonication-mediated death can occur by instantaneous cellular lysing and rapid cell death (within minutes post-exposure) due to wound-instigated necrosis; in addition, characteristics of rapidly induced controlled death modes were seen and found to be non-caspase-mediated within an hour after sonication ended.

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world and Taiwan. The major factors involved in the molecular pathogenesis for the development of HCC had been explored in recent years. An extensive array of growth factors and their receptors had been identified and may act as positive and negative modulators in different stages of hepatocarcinogenesis. Current therapeutic approaches for HCC include surgical resection (include liver transplantation), trans-arterial embolization (TAE), alcohol injection, etc. However, the effect is limited due to most of the HCC patients present with advanced stages of the disease. Therefore, this underscores the need for the development of novel therapeutic strategies. It is pivotal to set up an orthotopic hepatoma model for the development of novel intervention strategies for HCC. Under the guidance of ultrasound, we are able to create hepatoma in the liver lobe of Sprague-Dawley (SD) rats by injection of Novikoff (N1-S1) hepatoma cells. In addition, sonographic technique was employed for the monitoring of tumor growth in this animal model in the following subprojects. The continuous, non-invasive measurement of orthotopic hepatoma development will be a valuable tool for the evaluation of effects of drugs for treatment of HCC. In Chapter 1, the study employed a relatively non-invasive approach to establish an orthotopic HCC model in immune-competent rats. This was done by ultrasound-guided implantation of cancer cells and the model was used to evaluate the therapeutic efficacy of short-term and low-dose epirubicin chemotherapy. Ultrasound-guided implantation of Novikoff hepatoma cells led to the formation of orthotopic HCC in 60.4% of the SD rats. Moreover, tumor sizes measured by ultrasound significantly correlated with those measured by calipers after sacrificing the animals (P < 0.00001). The rate of tumor induction by ultrasound-guided implantation was comparable to that of laparotomy (55/91, 60.4% vs. 39/52, 75%) and no significant difference in sizes of tumor was noted between the two groups. Moreover, there was a significant correlation in tumor size measurement by ultrasound and computerized tomography. In tumor-bearing rats, short-term and low-dose epirubicin chemotherapy caused a significant reduction in tumor growth, and was found to be associated with enhanced apoptosis and attenuated proliferation as well as a decrease in microvessel density in tumors. In chapter 2, we investigated the chemopreventive effects of celecoxib in the growth of orthotopic rat HCC and the possible signal pathways involved. The status of COX-2 expression in rat Novikoff HCC was consistent with that in human HCC. Both Western blot and PCR tests had proved that N1-S1 was a HCC model presenting with low COX-2 enzymes in tumor cells. Then, low doses of celecoxib was shown to effectively inhibited the proliferation and increased the apoptosis of N1-S1 cells in vitro, which were also safe to the normal hepatocytes. Moreover, chemoprevention by celecoxib inhibiting the HCC tumor growth was shown in rat orthotropic HCC model. Tumor incidence was not affected by the celecoxib prevention, but, tumor weight was found significantly suppressed by the drug. Possible mechanisms of chemoprevention by celecoxib seen in the animal model were thought to be related to the anti-angiogenic, anti-proliferative and anti-hCSC characters of the drug. In chapter 3, we tried to test the combined inhibitory effects of low doses of celecoxib and epirubicin on the growth of HCC. Combined low doses of epirubicin and celecoxib was effective in inhibiting the hepatic cancer stem cells, tumor angiogenesis, tumor cell proliferation, as well as promoting cancer apoptosis. These are compatible with the effects of the individual drugs on HCC growth shown in the previous two chapters. In general, combination therapy expressed more effectiveness in tumor suppression and less bone marrow suppression than the individual drugs used alone. Taken together, ultrasound-guided implantation of Novikoff hepatoma cells is an effective means of establishing orthotopic HCC in SD rats, which is suitable and convenient for therapeutic trial of anti-HCC treatment. In the current study, we had proved the efficacies of low doses of two drugs, epirubicin and celecoxib, acting individually, as well as the combined effects of them in treating HCC in this model.

Fairy shrimp is an anostraca plankton which is raised for watching and scientific study. In recent year, due to the large requirement of fairy shrimp in the market, to increase the hatching rate of fairy shrimp is an important topic. It is found that when an Artemia Cysts hatched by light, the pigment absorption spectra in the Cysts match with the optical wavelength of the experimental incubators. Furthermore, the effect of ultrasound can stimulate the growth or activation of the fairy shrimp, when the ultrasonic parameters of frequency, intensity, exposure time and exposure period are properly controlled in the hatching experiments. This thesis is then focusing on the biological activities to increase the hatching rate of fairy shrimp by light and ultrasound exposure. This work investigates the light effect on the hatching experiment using different wavelength and intensity of LED light; in addition, Cysts is exposed to ultrasound by ultrasonic cleaner and transducer. The resonant frequency of the Cysts is obtained from Rayleig ¡VPlesset bubble activation formula. The radiation of the resonant and non-resonant regions during the hatching experiments are then set up by this resonant frequency for comparison. Finally, according to the experimental results, the correlations of hatching rate with light wavelength, light intensity, resonant frequency and ultrasound intensity are studied by Taguchi Method to understand the play role of the light and ultrasound. The research results show that the hatching rate is 25 % by lamp irradiation, and the maximum hatching rate is 42.5 % by blue light in the light experiment. In ultrasound experiment, the highest incubate percentage, 35 %, is obtained by ultrasound frequency 0.25 MHz and ultrasound intensity 39.2 mW/cm2. In the confirmed test, the blue light plus ultrasound frequency of 0.25 MHz plus ultrasound intensity of 30.9 mW/cm2 can let the incubate percentage up to 48.3%. This is the highest incubate percentage one can get from these experiments. Finally, the results of Taguchi analysis shows that the Confidence level of light affecting the hatching rate is 100%; thus, light source is the most critical factor to affect the hatching procedure. The results of this research can be referred by an endangered species or high economic value of species to increase the rate of hitching.

Bos indicus influenced primiparous heifers (n = 300) and yearling Beefmaster heifers (n = 172) were evaluated to determine relationships between serial carcass ultrasound traits and ability to breed in short (45 to 90 d) breeding seasons. Data collected included carcass ultrasound traits: ribeye area (REA), intramuscular fat (IMF), rump fat (UFAT), ribfat, weight, and body condition score taken at yearling age, pregnancy determination, before breeding, and after the breeding season when pregnancy status was recorded. A logistic regression analysis was used to determine the influence of ultrasound traits and body condition on pregnancy status. Odds ratios suggested the likelihood of primiparous cattle rebreeding would have been increased by 93% if IMF would have averaged 3.5% instead of 2.5% as yearlings, or an increase in the average ribfat as yearlings from 0.287 to 0.387 cm would have increased the odds of rebreeding by 88%. Increased average body condition score of 6.5 rather than 5.5 at 30 days postpartum in primiparous cows was estimated to have increased rebreeding 367%. The odds of yearling Beefmaster heifers successfully breeding during a 45-day season would have been increased by 73% (year 1) or 274% (year 2) by increasing REA 6.4 to 6.5 cm^2 at a year of age. Steers were serially scanned beginning at approximately 265 kg of body weight through harvest in 56 day +/- 6 intervals. Data collected included ultrasound measurements (ribeye area (REA), 12th rib fat thickness (RibFat), percent intramuscular fat (IMF), and rump fat (UFAT)), weight, and carcass data. Days to choice was calculated for each steer based on a linear regression. The IMF deposition was quantified as quadratic from scans 1-6 and linear when cattle were on full feed. Prediction models at scans 1, 2, 3, 4, 5, and 6 yielded R-square values of 0.20, 0.25, 0.41, 0.48, 0.59, and 0.49, respectively for days to choice. Odds ratios suggested that if steers in this study had averaged 3.78% at day 0 rather than 2.78, the odds of cattle grading premium choice or greater would have been increased by 300%.

This thesis demonstrates the practicability of using Resonant Ultrasound Spectroscopy (RUS) in combination with Finite Element Analysis (FEA) to determine the size and location of a defect in a material of known geometry and physical constants. Defects were analyzed by comparing the actual change in frequency spectrum measured by RUS to the change in frequency spectrum calculated using FEA. FEA provides a means of determining acceptance/rejection criteria for Non-Destructive Testing (NDT). If FEA models of the object are analyzed with defects in probable locations; the resulting resonant frequency spectra will match the frequency spectra of actual objects with similar defects. By analyzing many FEA-generated frequency spectra, it is possible to identify patterns in behavior of the resonant frequencies of particular modes based on the nature of the defect (location, size, depth, etc.). Therefore, based on the analysis of sufficient FEA models, it should be possible to determine nature of defects in a particular object from the measured resonant frequency. Experiments were conducted on various materials and geometries comparing resonant frequency spectra measured using RUS to frequency spectra calculated using FEA. Measured frequency spectra matched calculated frequency spectra for steel specimens both before and after introduction of a thin cut. Location and depth of the cut were successfully identified based on comparison of measured to calculated resonant frequencies. However, analysis of steel specimens with thin cracks, and of ceramic specimens with thin cracks, showed significant divergence between measured and calculated frequency spectra. Therefore, it was not possible to predict crack depth or location for these specimens. This thesis demonstrates that RUS in combination with FEA can be used as an NDT method for detection and analysis of cracks in various materials, and for various geometries, but with some limitations. Experimental results verify that cracks can be detected, and their depth and location determined with reasonable accuracy. However, experimental results also indicate that there are limits to the applicability of such a method, the primary one being a lower limit to the size of crack – especially thickness of the crack - for which this method can be applied.

New elastographic techniques such as poroelastography and viscoelasticity imaging aim at imaging the temporal mechanical behavior of tissues. These techniques usually involve the use of curve fitting methods as applied to noisy data to estimate new elastographic parameters. As of today, however, image quality performance of these new elastographic imaging techniques is still largely unknown due to a paucity of data and the lack of systematic studies that analyze performance limitations of estimators suitable for these novel applications. Furthermore, current elastographic implementations of poroelasticity and viscoelasticity imaging methods are in general too slow and not optimized for clinical applications. In this paper, we propose a new elastographic time constant (TC) estimator, which is based on the use of the Least Square Error (LSE) curve-fitting method and the Levenberg-Marquardt (LM) optimization rule as applied to noisy elastographic data obtained from a tissue under creep compression. The estimator's performance is analyzed using simulations and quantified in terms of accuracy, precision, sensitivity, signal-to-noise ratio (SNR) and speed. Experiments are performed as a proof of principle of the technical applicability of the new estimator on real experimental data. The results of this study demonstrate that the new elastographic estimator described in this thesis can produce highly accurate, sensitive and precise time constant estimates in real-time and at high SNR. In the future, the use of this estimator could allow real-time imaging of the temporal behavior of complex tissues and provide advances in lymphedema and cancer imaging.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成21年3月25日 靍見有史氏の博士論文として提出された