Effects of gas pockets on high-intensity focused ultrasound field

The paper describes experimental and numerical studies of the effects of gas pockets on a high-intensity focused ultrasound (HIFU) field. Air bubbles ranging from 0.8 to 2.4 mm in radius were produced in transparent polyacrylamide tissue-mimicking gels. A single-element 3.5-MHz HIFU transducer was used to sonicate the gel phantoms. The changes in the HIFU beam pattern for air bubbles at different positions were visualized by the Schlieren method. Quantitative measurements of pressure at the HIFU focus by a calibrated needle hydrophone showed considerable reduction in the focal pressure with the presence of an air pocket. The presence of a single 1.2-mm-radius air bubble, at a 5 mm axial pre-focal position, reduced the focal intensity by 50% and increased the lateral focal dimension by 50%. For air bubbles at pre-focal position close to the focus, lesion formation was observed not at the theoretical focus, but in front of the air bubble and the air bubble became a barrier for the post-focal ultrasound propagation. The effects of reflection were simulated numerically and were compared with the experiments. The results can be used as guidelines for evaluation of potential safety concerns produced by trapped gas-pockets in various HIFU therapies.     

In vitro and in vivo brain ablation created by high-intensity focused ultrasound and monitored by MRI

In this paper, magnetic resonance imaging (MRI) is investigated for monitoring small and large lesions created by high-intensity focused ultrasound (HIFU) in freshly excised lamb brain and in rabbit brain in vivo. A single-element spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating at 1 MHz was used. A prototype MRI-compatible positioning device that is used to navigate the transducer is described. The effects of HIFU were investigated using T1-W and T2-W fast spin echo (FSE) and fluid-attenuated inversion recovery (FLAIR). T2-W FSE and FLAIR show better anatomical details within the brain than T1-W FSE, but with T1-W FSE, the contrast between lesion and brain is higher for both thermal and bubbly lesions. The best contrast between lesion and brain with T1-W FSE is obtained with TR above 500 ms, whereas with T2-W FSE, the best contrast is observed between 40 and 60 ms. The maximum contrast to noise ratio (CNR) measured with T1-W FSE was approximately 20. With T2-W FSE, the corresponding CNR was approximately 12. With this system, we were able to create large lesions (by producing overlapping lesions), and it was possible to monitor these lesions with MRI with excellent contrast. The length of the lesions in vivo brain was much higher than the length in vitro, indicating that the penetration in the in vitro brain is limited, possibly by reflection due to trapped bubbles in the blood vessels. This paper demonstrates that HIFU has the potential to treat brain tumors in humans. This could be done either using a single-element transducer with a frequency around 1 MHZ or using a multi-element transducer.     

Finite-element analysis of temperature rise and lesion formation from catheter ultrasound ablation transducers

A model using finite-element analysis (FEA) has been developed to calculate the temperature rise in tissue from intracardiac ultrasound ablation catheters and to predict if this temperature rise is adequate for producing a lesion in the tissue. In the model, acoustic fields are simulated with Field II, and heat transfer is modeled with an FEA program. To validate the model, we compare its results to experimental results from an integrated, real-time three-dimensional (3-D) ultrasound imaging and ultrasound ablation catheter. The ultrasound ablation transducer is a ring transmitting at 10 MHz capable of producing an acoustic intensity of 16 W/cm2. It was used to ablate four lesions in tissue, and temperature rise as a function of time was monitored by embedded thermocouples. The average absolute difference between final temperatures predicted by FEA and those measured is 1.95 +/- 0.72 degrees C. Additionally, model and experimental lesion size are in good agreement. The model then is used to design a new ultrasound catheter with a 7.5 MHz linear phased array for ablation. Eight designs are modeled, and acoustic intensity, temperature rise, and ablation ability are compared.     

Annular phased-array high-intensity focused ultrasound device for image-guided therapy of uterine fibroids

An ultrasound (US), image-guided high-intensity focused ultrasound (HIFU) device was developed for noninvasive ablation of uterine fibroids. The HIFU device was an annular phased array, with a focal depth range of 30-60 mm, a natural focus of 50 mm, and a resonant frequency of 3 MHz. The in-house control software was developed to operate the HIFU electronics drive system for inducing tissue coagulation at different distances from the array. A novel imaging algorithm was developed to minimize the HIFU-induced noise in the US images. The device was able to produce lesions in bovine serum albumin-embedded polyacrylamide gels and excised pig liver. The lesions could be seen on the US images as hyperechoic regions. Depths ranging from 30 to 60 mm were sonicated at acoustic intensities of 4100 and 6100 W/cm2 for 15 s each, with the latter producing average lesion volumes at least 63% larger than the former. Tissue sonication patterns that began distal to the transducer produced longer lesions than those that began proximally. The variation in lesion dimensions indicates the possible development of HIFU protocols that increase HIFU throughput and shorten tumor treatment times.     

Design and characterization of dual-curvature 1.5-dimensional high-intensity focused ultrasound phased-array transducer

A dual-curvature focused ultrasound phased-array transducer with a symmetric control has been developed for noninvasive ablative treatment of tumors. The 1.5-D array was constructed in-house and the electro-acoustic conversion efficiency was measured to be approximately 65%. In vitro experiments demonstrated that the array uses 256 independent elements to achieve 2-D wide-range high-intensity electronic focusing.     

Numerical simulations of heating patterns and tissue temperature response due to high-intensity focused ultrasound

The results of this paper show-for an existing high intensity, focused ultrasound (HIFU) transducer-the importance of nonlinear effects on the space/time properties of wave propagation and heat generation in perfused liver models when a blood vessel also might be present. These simulations are based on the nonlinear parabolic equation for sound propagation and the bio-heat equation for temperature generation. The use of high initial pressure in HIFU transducers in combination with the physical characteristics of biological tissue induces shock formation during the propagation of a therapeutic ultrasound wave. The induced shock directly affects the rate at which heat is absorbed by tissue at the focus without significant influence on the magnitude and spatial distribution of the energy being delivered. When shocks form close to the focus, nonlinear enhancement of heating is confined in a small region around the focus and generates a higher localized thermal impact on the tissue than that predicted by linear theory. The presence of a blood vessel changes the spatial distribution of both the heating rate and temperature.     

Large improvement of the electrical impedance of imaging and high-intensity focused ultrasound (HIFU) phased arrays using multilayer piezoelectric ceramics coupled in lateral mode

With a change in phased-array configuration from one dimension to two, the electrical impedance of the array elements is substantially increased because of their decreased width (w)-to-thickness (t) ratio. The most common way to compensate for this impedance increase is to employ electrical matching circuits at a high cost of fabrication complexity and effort. In this paper, we introduce a multilayer lateral-mode coupling method for phased-array construction. The direct comparison showed that the electrical impedance of a single-layer transducer driven in thickness mode is 1/(n2(1/(w/t))2) times that of an n-layer lateral mode transducer. A large reduction of the electrical impedance showed the impact and benefit of the lateral-mode coupling method. A one-dimensional linear 32-element 770-kHz imaging array and a 42-element 1.45-MHz high-intensity focused ultrasound (HIFU) phased array were fabricated. The averaged electrical impedances of each element were measured to be 58 Ω at the maximum phase angle of -1.2° for the imaging array and 105 Ω at 0° for the HIFU array. The imaging array had a center frequency of 770 kHz with an averaged -6-dB bandwidth of approximately 52%. For the HIFU array, the averaged maximum surface acoustic intensity was measured to be 32.8 W/cm2 before failure.     

Design and characterization of a real-time angular scatter ultrasound imaging system

A novel ultrasound imaging system has been implemented using two 32-element linear phased array transducers oriented at an angle of 40 degrees to one another. The system simultaneously acquires and displays, in real time, a conventional backscatter image and an angular scatter image formed using side-scattered echoes from the same region. The design of the system is shaped by the influence of the scatter angle on the spatial resolution and receive signal processing requirements of the instrument. The subtended scatter angles are restricted to values >90 degrees to ensure that the angular scatter receiver effectively tracks the transmitted pulse and that the spatial resolution in the two images is comparable. The system is sufficiently tolerant of small variations in the average acoustic velocity of the medium to guarantee reliable pulse tracking in biomedical applications. The angular scatter signal magnitude is significantly weighted by the directivity of the receive array. The imaging system will most effectively demonstrate angular variations in scattering at scatter angles between 125 and 145 degrees , where the angular response of the receiver is near its peak.     

Feasibility of noncontact intracardiac ultrasound ablation and imaging catheter for treatment of atrial fibrillation

Atrial fibrillation (AF) affects 1% of the population and results in a cost of 2.8 billion dollars from hospitalizations alone. Treatments that electrically isolate portions of the atria are clinically effective in curing AF. However, such minimally invasive catheter treatments face difficulties in mechanically positioning the catheter tip and visualizing the anatomy of the region. We propose a noncontact, intracardiac transducer that can ablate tissue and provide rudimentary imaging to guide therapy. Our design consists of a high-power, 20 mm by 2 mm, 128-element, transducer array placed on the side of 7-French catheter. The transducer will be used in imaging mode to locate the atrial wall; then, by focusing at that location, a lesion can be formed. Imaging of previously formed lesions could potentially guide placement of subsequent lesions. Successive rotations of the catheter will potentially enable a contiguous circular lesion to be created around the pulmonary vein. The challenge of intracardiac-sized transducers is achieving high intensities (300-5000 W/cm2) needed to raise the temperature of the tissue above 43 degrees C. In this paper, we demonstrate the feasibility of an intracardiac-sized transducer for treatment of atrial fibrillation. In simulations and proof-of-concept experiments, we show a 37 degrees C temperature rise in the lesion location and demonstrate the possibility of lesion imaging.     

MPEG compression of ultrasound RF channel data for a real-time software-based imaging system

Using software for beamforming in ultrasound systems provides high flexibility, and the large number of computations required in a software-based system can be performed in real time on a PC. However, the very large data transfer rate required from the ultrasound front-end to the PC host for real-time operation is a bottleneck which cannot be overcome without appropriate compression. Previous studies have examined JPEG compression of ultrasound RF channel data, but the schemes do not exploit temporal redundancy between adjacent frames. This study utilized MPEG technology to process the ultrasound RF data to increase the compression efficiency. Our results indicate that MPEG compression generally provides a better compression ratio than does JPEG compression. As an example, the compression ratio of MPEG compression in an 8-bit channel A/D data under 5 μm interframe displacement is smaller than 0.13, thus allowing real-time data transfer requirements to be met. Moreover, the compression efficiency for motions in different directions is shown to be highly dependent on the frame-to-frame correlation.     

用于高强度聚焦超声热消融的PAA模块:模块的制作及声学参数的测量

目的研制一种透明的用于高强度聚焦超声热消融的PAA模块,并对其声学参数进行测量。方法观察模块浓度的不同所致颜色与透明度的变化,并对PAA模块的声学特性包括密度、声速及声衰减进行测量。结果(1)PAA模块为透明的琥珀色,蛋白浓度越高,颜色越深,透明度越低。(2)PAA模块的密度与水相近,为1.0250g/cm3至1.0617g/cm3。声速与模块浓度之间有明显的相关性。声衰减从0.125dB/cm至0.329dB/cm,随着模块密度与探头频率的增加而增加。结论PAA模块是一种较好的用于高强度聚焦超声热消融的均质仿体,实验结果有较好的重复性。     

Near-infrared spectroscopic method for real-time monitoring of pharmaceutical powders during voiding

A near-infrared (NIR) spectroscopic method has been developed to monitor flowing pharmaceutical powders during their voiding and detect post-blending segregation. The method is capable of providing both chemical and physical information (particle size differences) on the flowing pharmaceutical powders. Particle size differences are widely recognized as the predominant driver for segregation. Pharmaceutical powders may segregate following blending as they are voided down pipes to compressing machines, increasing the variability of the drug content and dissolution of the final product tablets because of segregation. NIR diffuse reflectance spectra of pharmaceutical powders were obtained following voiding through a six-foot pipe. Spectral subtraction was used to eliminate baseline differences but maintain particle size differences. The NIR spectra indicated differences in the particle size of the flowing powder. Particle size differences were also tracked throughout the voiding of pharmaceutical powders by plotting the absorbance at 1536 nm. The method was also applied to the voiding of two layers of lactose particles with different particle sizes. The system described in this report provides an approach to study post-blending segregation in pharmaceutical powders and other relevant materials.     

High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts

Adult zebrafish is a well-known small animal model for studying heart regeneration. Although the regeneration of scars made by resecting the ventricular apex has been visualized with histological methods, there is no adequate imaging tool for tracking the functional recovery of the damaged heart. For this reason, high-frequency Doppler echocardiography using dual mode pulsed wave Doppler, which provides both tissue Doppler (TD) and Doppler flow in a same cardiac cycle, is developed with a 30 MHz high-frequency array ultrasound imaging system. Phantom studies show that the Doppler flow mode of the dual mode is capable of measuring the flow velocity from 0.1 to 15 cm s⁻¹ with high accuracy (p-value = 0.974 > 0.05). In the in vivo study of zebrafish, both TD and Doppler flow signals were simultaneously obtained from the zebrafish heart for the first time, and the synchronized valve motions with the blood flow signals were identified. In the longitudinal study on the zebrafish heart regeneration, the parameters for diagnosing the diastolic dysfunction, for example, E/Em < 10, E/A < 0.14 for wild-type zebrafish, were measured, and the type of diastolic dysfunction caused by the amputation was found to be similar to the restrictive filling. The diastolic function was fully recovered within four weeks post-amputation.     

Combined passive detection and ultrafast active imaging of cavitation events induced by short pulses of high-intensity ultrasound

The activation of natural gas nuclei to induce larger bubbles is possible using short ultrasonic excitations of high amplitude, and is required for ultrasound cavitation therapies. However, little is known about the distribution of nuclei in tissues. Therefore, the acoustic pressure level necessary to generate bubbles in a targeted zone and their exact location are currently difficult to predict. To monitor the initiation of cavitation activity, a novel all-ultrasound technique sensitive to single nucleation events is presented here. It is based on combined passive detection and ultrafast active imaging over a large volume using the same multi-element probe. Bubble nucleation was induced using a focused transducer (660 kHz, f-number = 1) driven by a high-power electric burst (up to 300 W) of one to two cycles. Detection was performed with a linear array (4 to 7 MHz) aligned with the single-element focal point. In vitro experiments in gelatin gel and muscular tissue are presented. The synchronized passive detection enabled radio-frequency data to be recorded, comprising high-frequency coherent wave fronts as signatures of the acoustic emissions linked to the activation of the nuclei. Active change detection images were obtained by subtracting echoes collected in the unnucleated medium. These indicated the appearance of stable cavitating regions. Because of the ultrafast frame rate, active detection occurred as quickly as 330 μs after the high-amplitude excitation and the dynamics of the induced regions were studied individually.     

Evaluation of accuracy of a theoretical model for predicting thenecrosed tissue volume during focused ultrasound surgery

The concept of thermal dose as a predictor for the size of the necrosed tissue volume during high-intensity focussed ultrasound surgery was tested. The sensitivity of the predicted lesion size to the uncertainties in the iso-dose constant, attenuation coefficient, and thermal dose threshold of necrosis was studied. The predicted lesion size appears to be independent of attenuation at some high attenuation values and certain depth in tissue. Thus, for a given target depth, a proper selection of frequency could minimize the lesion size variability due to uncertainty in the tissue attenuation. The predicted lesion size was less dependent on the uncertainties in the iso-dose constant and thermal dose of necrosis. The predictions of the model were compared with experimental data in rabbit muscle, and experimental data in cat and rat brain measured by others. The agreement was found to be good in most of the experiments. Similarly, the model was found to predict well the trends of increasing power and pulse duration     

Application of real-time holographic interferometry for analyzing samples and imaging processes during flat-capillary electrophoresis

Application of the real-time holographic interferometry technique to the analysis of liquid samples by means of electrophoresis in a flat capillary is demonstrated.     

Evaluation of thermal imaging system and thermal radiation detector for real-time condition monitoring of high power frequency converters

We have carried out at laboratory test to study the feasibility of using thermal radiation detectors for online thermal monitoring of electrical systems in wind
turbines. A 25 kW frequency converter is instrumented with a thermal camera, operating in the 8–14 lm wavelength range, and a single-pixel thermopile sensor, operating in the 4–8 lm wavelength range, to monitor the temperature development of the power electronics under various load sequences. Both systems performed satisfactorily with insignificant temperature deviations when compared to data from calibrated point contact sensor. With spatial averaging over a 7 mm 9 7 mm for the camera and temporal averaging over 60 s for the thermopile sensor, we reduce the root mean square noise to 45 mK
and 68 mK respectively. The low cost and simple operation of the thermopile sensor make it very attractive for condition monitoring applications, whereas the attractive feature of the camera is the possibility of multi-point or distributed temperature measurements.     

Insight of the optical property of laccase during polymerics formation for application in real-time biosensing

As a kind of biofunctional material, laccases with superior intrinsic optical property are garnering substantial interest in enzyme-based optical biosensing due to their great potential use in the field of food, environment and industry. However, it is still unclear as to the variation mechanism of enzyme intrinsic optical property, and thus limits the application. For exploring the variation mechanism, the current study presents the optical characterization of Agaricus bisporus laccase and focus on real-time monitoring polymerics formation, both theoretically and experimentally, in order to lay a foundation for laccase-based optical biosensing application. According to bioinformatics analysis, the results show that the target laccase has conserved copper binding site, and the related amino acid residues possibly have positive effect on the florescence of Typ in this region. On the basis of experimental characterization, the results show that the enzyme displays an obvious absorption peak at approximately 400 nm (optimal pH 7.0), and the strongest fluorescence of enzyme centers at around the excitation wavelength of 280 nm and emission wavelength of 340 nm (optimal pH 6.0); organic ethanol serves as an active enhancer toward the absorbance of enzyme, especially the high concentration ethanol (50%) can achieve above twofold enhancement on the enzyme absorbance compared to that of the non-addition in the examined condition, while Cu²⁺ acts as a strong inhibitor for the enzyme fluorescence due to the above 95% inhibition. Overall, the work suggests that the stably increased absorbance and decreased fluorescence of enzyme can serve as dual standard for optical biosensing which will benefit in improving the flexibility and accuracy of sensing.

     

A condition monitoring approach for real-time monitoring of degrading systems using Kalman filter and logistic regression

We present a new model for reliability analysis that is able to employ condition monitoring data in order to simultaneously monitor the latent degradation level and track failure progress over time. The method presented in this paper is a bridge between Bayesian filtering and classical binary classification, both of which have been employed successfully in various application domains. The Kalman filter is used to model a discrete-time continuous-state degradation process that is hidden and for which only indirect information is available through a multi-dimensional observation process. Logistic regression is then used to connect the latent degradation state with the failure process that is itself a discrete-space stochastic process. We present a closed-form solution for the marginal log-likelihood function and provide formulas for few important reliability measures. A dynamic cost-effective maintenance policy is finally introduced that can employ sensor signals for real-time decision-making. We finally demonstrate the accuracy and usefulness of our framework via numerical experiments.     

Application of in-line viscometer for in-process monitoring of microcrystalline cellulose-carboxymethylcellulose hydrogel formation during batch manufacturing

Physical stability and consistent dose delivery of pharmaceutical suspension formulations comprised of microcrystalline cellulose (MCC) and sodium carboxymethylcellulose (NaCMC) hydrogels is dependent on their rheological properties. To obtain the desired rheological characteristics, good control of the hydrogel dispersion in water is required. The goal of this study was to evaluate whether the XL7-100 Process Viscometer could be employed as a process analytical technology (PAT) tool to monitor the dispersion process in real time during batch manufacturing. Using this instrument, viscosity profiles were measured during the hydrogel processing for a range of operating conditions. It was confirmed that viscosity obtained by the XL7-100 Process Viscometer in the off-line mode, could be linearly correlated to that of the conventional Brookfield viscometer. In addition, the XL7-100 Process Viscometer was able to detect variations in the hydrogel concentrations as well as process conditions in real time. Under fixed operating conditions, the dynamic viscosity profile showed low variability and good inter-batch reproducibility for a properly dispersed hydrogel. For a well-validated mixing process, an off-trend in-line viscosity reading may be indicative of batch failure or poor dispersion homogeneity. Therefore, the in-line viscometer can be used in manufacturing to monitor the batch to batch consistency. However, it is not proven to be able to characterize the real-time structure formation of the hydrogel. It is recommended that the in-line viscometer be used as a complimentary tool along with the off-line rheometer for both efficient and effective in-process quality control of the MCC & NaCMC hydrogel dispersion.