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Our group has proposed the concept of subharmonic aided pressure estimation (SHAPE) utilizing microbubble-based ultrasound contrast agent signals for the noninvasive estimation of hydrostatic blood pressures. An experimental system for in vitro SHAPE was constructed based on two single-element transducers assembled confocally at a 60° angle to each other. Changes in the first, second and subharmonic amplitudes of five different ultrasound contrast agents were measured in vitro at static hydrostatic pressures from 0–186 mmHg, acoustic pressures from 0.35–0.60 MPa peak-to-peak and frequencies of 2.5–6.6 MHz. The most sensitive agent and optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Logiq 9 scanner (GE Healthcare, Milwaukee, WI). This implementation of SHAPE was then tested under dynamic-flow conditions and compared to pressure-catheter measurements. Over the pressure range studied, the first and second harmonic amplitudes reduced approximately 2 dB for all contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 9–14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations ( r2 = 0.98, p < 0.001). Optimal sensitivity was achieved at a transmit frequency of 2.5 MHz and acoustic pressure of 0.35 MPa using Sonazoid (GE Healthcare, Oslo, Norway). A Logiq 9 scanner was modified to implement SHAPE on a convex transducer with a frequency range from 1.5–4.5 MHz and acoustic pressures from 0–3.34 MPa. Results matched the pressure catheter ( r2 = 0.87). In conclusion, subharmonic contrast signals are a good indicator of hydrostatic pressure. Out of the five ultrasound contrast agents tested, Sonazoid was the most sensitive for subharmonic pressure estimation. Real-time SHAPE has been implemented on a commercial scanner and offers the possibility of allowing pressures in the heart and elsewhere to be obtained noninvasively.

Gate oxide and interface trap charges are critical parameters for device reliability and their generation and recovery are investigated under AC and DC oxide field stress on n-channel MOSFETs by C-V, I–V, and CP measurements. The interface traps generation is the same under both DC and AC stress but oxide charge trap generation is higher at AC stress than DC stress. The oxide charge and interface trap generation rate is independent of frequency from low to 10MHz but increase with stress time. The generated interface traps are positioned in the middle of the band gap and oxide traps are negatively charged and located in the upper half of the energy band gap due to the electron injection from the inversion layer. Both interface and oxide trap charges are characterized by high frequency and quasi-static C-V measurement.

Currently the feedback guidance of intracardiac radiofrequency ablation (RFA) is very limited, offering only a catheter electrode (not tissue) temperature estimation and a means to titrate radiofrequency (RF) power delivery to the tissue. Our “MicroLinear” (ML) forward imaging ultrasound catheter design, now at a true 9F (3mm) in size, has been optimized with several features to simultaneously permit a) high quality intracardiac steering and imaging, b) tracking of 3D position with electroanatomical mapping, c) RF ablation, and d) tissue thermal strain (TS) estimation for direct tissue temperature feedback. Two types of ML catheters have been built and tested in 3 porcine animal models. The first type, in its third generation, is based on a PZT transducer array; the second type, in its second generation, is based on a CMUT array with custom integrated interface circuitry. Both types of devices are true 9F in size and performed well in imaging tests in recent in vivo studies. Both the ML-PZT and ML-CMUT arrays, as described previously, have a fine pitch (65 and 63 micron respectively) 24 element phased arrays operating at 14 MHz which project a B-mode plane directly out from the tip of the catheter. Intracardiac imaging performance was documented to show that the very small array apertures of the ML design (1.2mm × 1.58mm, and 1.1mm × 1.4mm) permit good, high resolution imaging to depths as great as 4 cm. The ML-PZT catheter was equipped with a special low profile ablation tip which allowed simultaneous imaging and ablation at the distal end of the catheter. TS data were acquired during tissue ablations in right atrium (RA) and right ventricle (RV). The TS data of the RF ablations were processed off line. In vivo use of this new technology has shown for the first time the very substantial potential for a single, low profile catheter to simultaneously image within the heart and perform intracardiac ablation therapy with tissue temperature guidance produced from the incorporation of TS imaging. Work is underway to further assess the temperature estimation accuracy and to integrate the TS processing for real time displays.

A method to monitor ablative therapy by examining slope changes in the thermal strain curve caused by speed of sound with temperature is introduced. The variation of sound speed with temperature rise for most soft tissue follows a similar pattern to that of water. Unlike most liquids, the sound speed of tissue increases with temperature. However, at temperatures above about 50 °C, there is no further increase in the sound speed and the temperature coefficient may become slightly negative. For ablation therapy, an irreversible injury to tissue and a complete heart block occurs in the range of 48–50 °C for a short period in accordance with the well known Arrhenius equation. Using these two properties, we propose a potential tool to detect the moment when tissue damage occurs using the reduced slope in the thermal strain curve as a function of heating time. Using a prototype intracardiac echocardiography (ICE) array for imaging and a catheter for RF ablation, we were able to observe an obvious slope change in the thermal strain curve in an excised tissue sample. The method was further tested in-vivo, using a specially equipped ablation tip and an 11 MHz microlinear (ML) ICE array mounted on the tip of a catheter. As with in-vitro experiments, the thermal strain curve showed a plateau and a change in the sign of the slope.

A new and accurate approach to gate oxide reliability measurements for the determination of the gate oxide quality and lifetime estimation on MOSFET is presented. An accurate gate oxide thickness calculation by gate current provides oxide thickness variations better than conventional CV measurement. A gate oxide quality by gate current analysis is well correlated to the time dependent dielectric breakdown (TDDB) method. The results present that oxide lifetime is better at lower gate current in same oxide thickness where device process is same but different fabrication facilities (FAB).

The study of abrupt increases in magnetization with magnetic field known as metamagnetic transitions has opened a rich vein of new physics in itinerant electron systems, including the discovery of quantum critical end points with a marked propensity to develop new kinds of order. However, the electric analogue of the metamagnetic critical end point, a "metaelectric" critical end point has not yet been realized. Multiferroic materials wherein magnetism and ferroelectricity are cross-coupled are ideal candidates for the exploration of this novel possibility using magnetic-field (\emph{H}) as a tuning parameter. Herein, we report the discovery of a magnetic-field-induced metaelectric transition in multiferroic BiMn$_{2}$O$_{5}$ in which the electric polarization (\emph{P}) switches polarity along with a concomitant Mn spin-flop transition at a critical magnetic field \emph{H}$_{\rm c}$. The simultaneous metaelectric and spin-flop transitions become sharper upon cooling, but remain a continuous crossover even down to 0.5 K. Near the \emph{P}=0 line realized at $\mu_{0}$\emph{H}$_{\rm c}$$\approx$18 T below 20 K, the dielectric constant ($\varepsilon$) increases significantly over wide field- and temperature (\emph{T})-ranges. Furthermore, a characteristic power-law behavior is found in the \emph{P}(\emph{H}) and $\varepsilon$(\emph{H}) curves at \emph{T}=0.66 K. These findings indicate that a magnetic-field-induced metaelectric critical end point is realized in BiMn$_2$O$_5$ near zero temperature., Comment: 6 pages, 3 figures

Photoacoustic signals, detected by a transducer array, need to be beamformed for subsequent use in a limited view angle tomography such as B-scan imaging. In the presence of the light scattering or phase aberration, the spatial resolution and contrast in the photoacoustic images are degraded. Phase aberration due to tissues with inhomogeneous acoustic speeds is a major source for image degradation. However, a constant speed of sound (e.g., 1540 m/s) is typically assumed in photoacoustic imaging. Such an assumption can affect the quality of photoacoustic image since changes in sound velocity cause significant phase errors in beamforming. An adaptive weighting method such as coherence factor (CF) technique can improve the ultrasound and photoacoustic image quality significantly. In addition, photoacoustic images can be further improved by applying adaptive beamforming techniques developed for ultrasound imaging. In this study, an adaptive photoacoustic image reconstruction technique that combines an adaptive weighting factor (CF) and an adaptive apodization called minimum variance method (MV) is introduced. Although MV method calculates the optimal apodization weighting factors which minimize the variance of the beamformed signal, it can lead to unexpected weighting factors since it is data dependant. In this case, CF weighting can help to avoid this problem by weighting the output from the MV method based on signal coherence. Simulations were performed to analyze the spatial resolution using a point targets and to demonstrate improvement in phase aberration correction. Numerical studies demonstrated the superior performance of MV adaptive method combined with CF weighting.

Ultrasonography constructs pictures of areas inside the body needs in diagnosis by bouncing ultrasound off internal tissues or organs. In constructing an ultrasonographic image, the weakness of bounding signals induces noises and detailed differences of brightness, so that having a difficulty in detecting and diagnosing with the naked eyes in the analysis of ultrasonogram. Especially, the difficulty is extended when diagnosing muscle areas by using ultrasonographic images in the musculoskeletal test. In this paper, we propose a novel image processing method that computationally extracts a muscle area from an ultrasonographic image to assist in diagnosis. An ultrasonographic image consists of areas corresponding to various tissues and internal organs. The proposed method, based on features of intensity distribution, morphology and size of each area, extracts areas of the fascia, the subcutaneous fat and other internal organs, and then extracts a muscle area enclosed by areas of the fascia. In the extraction of areas of the fascia, a series of image processing methods such as histogram stretching, multiple operation, binarization and area connection by labeling is applied. A muscle area is extracted by using features on relative position and morphology of areas for the fascia and muscle areas. The performance evaluation using real ultrasonographic images and specialistspsila analysis show that the proposed method is able to extract target areas being approximate to real muscle areas.

Photothermal therapy is a noninvasive, targeted, laser-based technique for cancer treatment. During photothermal therapy, light energy is converted to heat by tumor-specific photoabsorbers. The corresponding temperature rise causes localized cancer destruction. For effective treatment, however, the presence of photoabsorbers in the tumor must be ascertained before therapy and thermal imaging must be performed during therapy. This study investigates the feasibility of guiding photothermal therapy by using photoacoustic imaging to detect photoabsorbers and to monitor temperature elevation. Photothermal therapy is carried out by utilizing a continuous wave laser and metal nanocomposites broadly absorbing in the near-infrared optical range. A linear array-based ultrasound imaging system is interfaced with a nanosecond pulsed laser to image tissue-mimicking phantoms and ex-vivo animal tissue before and during photothermal therapy. Before commencing therapy, photoacoustic imaging identifies the presence and spatial location of nanoparticles. Thermal maps are computed by monitoring temperature-induced changes in the photoacoustic signal during the therapeutic procedure and are compared with temperature estimates obtained from ultrasound imaging. The results of our study suggest that photoacoustic imaging, augmented by ultrasound imaging, is a viable candidate to guide photoabsorber-enhanced photothermal therapy.

In this study, we characterized the two-dimensional lattice of bovine serum albumin (BSA) as a chemical and physical barrier against bacterial adhesion, using fluorescence microscopy and atomic force microscopy (AFM). The lattice of BSA on glass surface was fabricated by micro-contact printing (microCP), which is a useful way to pattern a wide range of molecules into microscale features on different types of substrates. The contact-mode AFM measurements showed that the average height of the printed BSA monolayer was 5-6 nm. Escherichia coli adhered rapidly on bare glass slide, while the bacterial adhesion was minimized on the lattices in the range of 1-3 microm(2). Especially, the bacterial adhesion was completely inhibited on a 1 microm(2) lattice. The results suggest that the anti-adhesion effects are due by the steric repulsion forces exerted by BSA.

In photothermal therapy, a localized temperature increase is achieved by using a continuous wave laser and optically tuned metal nanoparticles. However, the successful outcome of therapy depends on identifying the presence of nanoparticles in the tumor before therapy and monitoring temperature rise during the photothermal procedure. In this paper, we investigate the utility of photoacoustic and ultrasound imaging to guide photothermal therapy. Differences in the optical properties of tissue, enhanced by the presence of nanoparticles, provide a contrast for photoacoustic imaging. Thus, an uptake of nanoparticles in the tumor can be detected by monitoring a photoacoustic image over time. A temperature rise causes the photoacoustic signal amplitude to increase. In addition, a temperature change also leads to time shifts in an ultrasound signal, primarily due to the change in speed of sound. Therefore, by measuring the change in the photoacoustic signal, and differential motion of ultrasound speckle, the temperature rise during photothermal therapy can be computed. Combined imaging was performed with a tunable pulsed laser and an array-based ultrasound transducer. Experiments were carried out on ex-vivo animal tissue injected with composite and broadly absorbing gold nanoparticles. The photoacoustic imaging identified the presence of nanoparticles in tissue. In addition, a localized temperature increase, obtained during therapy, was monitored using photoacoustic and ultrasound imaging. The temperature profiles, obtained by both imaging techniques, were spatially and temporally co-registered. Therefore, the experimental results suggest that photoacoustic and ultrasound imaging can be used to guide and monitor photothermal therapy.

Due to its excellent spatial resolution, fast and reliable performance, cost and wide availability, ultrasound should be considered the imaging modality of choice for many applications including molecular imaging. However, ultrasound imaging cannot image molecular content of tissue due to trade-off between spatial resolution and penetration depth. Consequently, contrast agents have been developed both to enhance the contrast of ultrasound images and to make the images molecularly specific. Most ultrasound contrast agents, however, are micrometer sized and may not be applicable to wide range of pathology-specific cellular and molecular imaging. We have developed an imaging technique - magneto-motive ultrasound (MMUS) imaging, capable of imaging magnetic nanoparticles subjected to time-varying magnetic field. The result of our studies indicate that magnetically excited nanoparticles can be used as contrast agents in magneto-motive ultrasound imaging thus expanding the role of ultrasound imaging to cellular scales and molecular sensitivity.

In elasticity imaging, the ultrasound frames acquired during tissue deformation are analyzed to estimate the internal displacements and strains. If the deformation rate is high, high-frame-rate imaging techniques are required to avoid the severe decorrelation between the neighboring ultrasound images. In these high-frame-rate techniques, however, the broader and less focused ultrasound beam is transmitted and, hence, the image quality is degraded. We quantitatively compared strain images obtained using conventional and ultrafast ultrasound imaging methods. The performance of the elasticity imaging was evaluated using custom-designed, numerical simulations. Our results demonstrate that signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and spatial resolutions in displacement and strain images acquired using conventional and ultrafast ultrasound imaging are comparable. This study suggests that the high-frame-rate ultrasound imaging can be reliably used in elasticity imaging if frame rate is critical.

To perform ultrasound imaging using an array transducer, a focused ultrasound beam is transmitted in a particular direction within the tissue and the received backscattered ultrasound wave is then dynamically focused at every position along the beam. The ultrasound beam is scanned over the desired region to form an image. The photoacoustic imaging, however, is distinct from conventional ultrasound imaging. In photoacoustic imaging the acoustic transients are generated simultaneously in the entire volume of the irradiated tissue – no transmit focusing is possible due to light scattering in the tissue. The photoacoustic waves are then r ecorded on every element of th e ultrasound tran sducer array at once and processed to form an image. Therefore, compared to ultrasound imaging, photoacoustic imaging can utilize dynamic receive focusing only. In this paper, we describe the image formation algorithms of the array-based photoacoustic and ultrasound imaging system and present me thods to improve the quality of photoacoustic images. To evaluate the performance of photoacoustic imaging using an array transducer, numerical simulations and phantom experiments were performed. First, to evaluate spatial resolution, a point source was imaged using a combined ultrasound and photoacoustic imaging system. Next, image quality was assessed by imaging tissue imaging phantoms containing a circular inclusion. Finally, the photoacoustic and ultrasound images from the combined imaging system were analyzed. Keywords: Photoacoustic imaging, ultrasound imaging, array transducer, beamforming, image formation, image reconstruction, delay and sum

Tissue engineering is an interdisciplinary field that combines various aspects of engineering and life sciences and aims to develop biological substitutes to restore, repair or maintain tissue function. Currently, the ability to have quantitative functional assays of engineered tissues is limited to existing invasive methods like biopsy. Hence, an imaging tool for non-invasive and simultaneous evaluation of the anatomical and functional properties of the engineered tissue is needed. In this paper we present an advanced in-vivo imaging technology - ultrasound biomicroscopy combined with complementary photoacoustic and elasticity imaging techniques, capable of accurate visualization of both structural and functional changes in engineered tissues, sequential monitoring of tissue adaptation and/or regeneration, and possible assistance of drug delivery and treatment planning. The combined imaging at microscopic resolution was evaluated on tissue mimicking phantoms imaged with 25 MHz single element focused transducer. The results of our study demonstrate that the ultrasonic, photoacoustic and elasticity images synergistically complement each other in detecting features otherwise imperceptible using the individual techniques. Finally, we illustrate the feasibility of the combined ultrasound, photoacoustic and elasticity imaging techniques in accurately assessing the morphological and functional changes occurring in engineered tissue.

A hybrid imaging system is proposed for cancer detection, diagnosis and therapy monitoring by integrating three complementary imaging techniques - ultrasound, photoacoustic and elasticity imaging. Indeed, simultaneous imaging of the anatomy (ultrasound imaging), cancer-induced angiogenesis (photoacoustic imaging) and changes in biomechanical properties (elasticity imaging) of tissue is based on many synergistic features of these modalities and may result in a unique and important imaging tool. To facilitate the design and development of a real-time imaging system for clinical applications, we have investigated the core components of the imaging system using numerical simulations. Differences and similarities between each imaging technique were considered and contrasted. The results of our study suggest that the integration of ultrasound, photoacoustic and elasticity imaging is possible using a custom designed imaging system.

An advanced in-vivo imaging technology; namely, combined ultrasound, elasticity and photoacoustic imaging, capable of visualizing both structural and functional properties of living tissue, is presented. This hybrid imaging technology is based on the fusion of the complementary imaging modalities and takes full advantage of the many synergistic features of these systems. To highlight fundamental differences and similarities between the imaging systems and to appreciate advantages and limitations of each imaging system, the basic physics of each imaging system is described. The experimental aspects of combined imaging including hardware, signal and image processing algorithms, etc. are presented. Noise and primary artifacts associated with each imaging modality and combined imaging system are analyzed, and techniques to increase and optimize contrast-to-noise and signal-to-noise ratios in the images are discussed. Finally, biomedical and clinical applications of the combined ultrasound, elasticity and photoacoustic imaging ranging from macroscopic to microscopic imaging of pathology are demonstrated and discussed

We investigated the performance of the conventional and high frame rate ultrasound imaging techniques for strain and elasticity imaging. High frame rate imaging is necessary to track fast deformation in elasticity imaging, but the ultrasound image quality is known to be compromised. Both numerical and experimental studies were performed using point targets and tissue mimicking phantoms. The results of our study confirm that the signal to noise ratio (SNR), contrast to noise ratio (CNR), and axial/lateral resolution of the displacement and strain images acquired using high frame rate ultrasound imaging are comparable with those obtained using the conventional imaging. Thus, the high frame rate ultrasound imaging can be reliably used for both static and dynamic elasticity imaging if the frame rate to capture the internal tissue motion is critical

Changes in tissue mechanical (elasticity, viscosity, etc.) properties are often associated with tissue pathology. In this paper, we present an ultrasound method capable of imaging the shear viscosity of soft tissue. This method is based on the measurement of creep function where tissue viscosity can be assessed by measuring slowly varying residual mechanical deformations induced by steady external forces rapidly applied at the surface. A finite element analysis of internal deformations of inhomogeneous viscoelastic medium was performed to investigate the capabilities of viscosity imaging. Then the ultrasound measurements of creep function were performed in the tissue sample (bovine muscle) to remotely assess viscoelastic properties of the tissue. The results of numerical and experimental studies suggest that time-dependent deformations can be measured with ultrasound to estimate and image both tissue elasticity and viscosity.

Objectives: Dental implants installation in patients with diabetes remains controversial as altered bone healing around implants has been reported. And little is known about the biological factors involved in bone healing around implants. The present study aimed to investigate the biological markers around immediately placed implants in rats with controlled and uncontrolled diabetes. Materials and Methods: Twenty rats (40 sites) were divided into the control, insulin-treated and diabetic groups. The rats received streptozotocin (60mg/kg) to induce diabetes; animals in the insulin-treated group also received three units of subcutaneous slow-release insulin. Two threaded titanium alloy implant (1.2×3 mm) were placed in the extraction socket of the both maxillary first molars and allowed for healing. Bone blocks including implant were harvested at 3 days, 1, 2 and 4 weeks. The levels of bone morphogenetic protein (BMP)-4, transforming growth factor (TGF)-β1, osteocalcin (OC) and osteonectin (ON) were measured in the peri-implant osseous samples by RT-PCR. Results: The BMP-4 level increased immediately in all groups by day 3, then decreased abruptly in the control and the insulin-treated groups. However, by week 4, all groups showed mostly the same amount of BMP-4 expression. The level of TGF-β1 also instantly increased by day 3 in the insulin-treated group. This level elevated again reaching the same values as the control group by week 4, but was not as high as the diabetic group. In addition, the expression of OC and ON in the control and insulin-treated groups was higher than that of the diabetic group at 2 weeks and 4 weeks, indicating active bone formation in these groups. Conclusion: The immediate placement of titanium implants in the maxilla of diabetic rat led to an unwanted bone healing response. Conclusively, the results of this study suggest that immediate implant insertion in patients with poorly controlled diabetes might be contraindicated.

An adaptive photoacoustic image reconstruction technique that combines coherence factor (CF) weighting and the minimum variance (MV) method is introduced. The backprojection method is widely used to reconstruct photoacoustic tomography images. Owing to the scattering of light, the quality of the photoacoustic imaging can be degraded. CF, an adaptive weighting technique, is known to improve the lateral resolution of photoacoustic images. In addition, an MV adaptive beamforming method can further improve the image quality by suppressing signals from off-axis directions. Experimental studies are performed to quantify the spatial resolution and contrast of the adaptive photoacoustic beamforming methods.

We report the extraction of silicon via a carbothermal reduction process using a CO2 laser beam as a heat source. The surface of a mixture of silica and carbon black powder became brown after laser beam irradiation for a few tens of seconds, and clear peaks of crystalline silicon were observed by Raman shift measurements, confirming the successful carbothermal reduction of silica. The influence of process parameters, including the laser beam intensity, radiation time, nitrogen gas flow in a reaction chamber, and the molar ratios of silica/carbon black of the mixture, on the carbothermal reduction process is explained in detail.

C-phycocyanin, a natural blue-colored pigment-protein complex was explored as a novel photosensitizer for use in low-level laser therapy under 625-nm laser illumination. C-phycocyanin produced singlet oxygen radicals and the level of reactive oxygen species (ROS) were raised in extended time of treatment. It did not exhibit any visible toxic effect in the absence of light. Under 625-nm laser irradiation, c-phycocyanin generated cytotoxic stress through ROS induction, which killed MDA-MB-231 breast cancer cells depending on concentrations. Different fluorescent staining of laser-treated cells explored apoptotic cell death characteristics like the shrinking of cells, cytoplasmic condensation, nuclei cleavage, and the formation of apoptotic bodies. In conclusion, phycocyanin is a non-toxic fluorescent pigment that can be used in low-level light therapy.