时间反转方法用于高强度聚焦超声的焦点偏移补偿

传统的高强度聚焦超声(HIFU)治疗中实际焦点和预设焦点容易出现偏移,为考察时间反转方法对HIFU治疗中焦点偏移的补偿效果,采用时域有限差分方法求解Westervelt方程,建立高强度聚焦声场数值模型。数值计算得到在人体软组织中进行HIFU治疗时,采用时间反转方法后焦点偏移距离最大仅为1.6 mm。脂肪层厚度及声源强度改变对时间反转聚焦精度影响不大,F数(焦点距离同换能器孔径的比值)降低时,焦点偏移减小。研究表明在人体软组织吸收系数和非线性系数范围内,时间反转方法可有效补偿焦点偏移,达到更好的聚焦效果。      

剪切波对HIFU经颅聚焦形成温度场影响的数值仿真研究

在高强度聚焦超声经颅治疗时,既有纵波又有剪切波,为了保障该治疗方法的安全有效性,有必要分析剪切波对HIFU治疗温度场的影响。该文基于人体头颅CT数据和曲率半径为150 mm的256阵元的半球相控换能器建立三维高强度聚焦超声经颅声波传播模型,利用时域有限差分法结合Westervelt声波非线性传播方程、动量方程、质量守恒方程和Pennes生物热传导方程数值仿真其形成温度场,研究在相同输入功率、不同聚焦角度条件下对应阵元数进行激励时,剪切波对换能器形成温度场的影响。结果表明,随换能器聚焦角度减小,在几何焦点处形成的焦域面积逐渐增大,考虑剪切波形成的温度场达到65?C所需时间逐渐延长,焦点前移程度越大;在相同聚焦角度条件下,考虑剪切波的温度场达到65?C所需时间更短,旁瓣更少,在颅骨处的温度更高,对焦点前移几乎没有影响;随换能器聚焦角度减小,考虑剪切波的模型形成的焦域面积变化范围更大;幂指数函数形式对不同聚焦角度下焦域面积大小的拟合优度高,可预测不同聚焦角度换能器形成的焦域面积。     

微泡对高强度聚焦超声声压场影响的仿真研究*

微泡对高强度聚焦超声(HIFU)治疗焦域具有增效作用,而HIFU治疗中不同声学条件下微泡对HIFU形成声压场的影响尚不清楚。本文基于气液混合声波传播方程、Keller气泡运动方程、时域有限差分(FDTD)法和龙格-库塔(RK)法数值仿真研究输入声压、激励频率、气泡初始空隙率和气泡初始半径对HIFU形成声压场的影响。研究结果表明,随着输入声压的增大,焦点处声压升高但焦点处最大声压与输入声压的比值减小,焦点位置几乎不变;随着激励频率和气泡初始半径的增大,焦点处声压升高且焦点位置向远离换能器方向移动;随着气泡初始空隙率的增大,焦点处声压降低且焦点位置向换能器方向移动。     

A feasibility study of temperature rise measurement in a tissue phantom as an alternative way for characterization of the therapeutic high intensity focused ultrasonic field

The feasibility that temperature field measurements in vitro as an alternative way to characterize the high intensity focused ultrasound (HIFU) field used in therapeutic applications has been explored in a phantom study. Thermocouples (copper-constantan, diameter 0.125 mm) are embedded in a phantom filled with tissue mimicking material that simulates the thermal and acoustic properties of soft-tissue. The temperature rises as a function of ultrasound exposure time near the focus of a HIFU transducer (1.1 MHz, active radius a = 32 mm, geometric focal length = 62 mm) of various acoustic powers up to 30 W are measured and compared with predicted values using a simple nonlinear Gaussian model. The experimental results can be explained well by the model if no acoustic cavitation takes place. When the acoustic power become higher (>5 W) and the local temperature elevation >15 °C and the local temperature is >40 °C at the focal point, cavitation vapor bubbles appear. The presence of the cavitation bubbles may increase the temperature rise rate initially. The bubble aggregates may form along the beam axis under sonication and then eventually makes the temperature elevation reach a saturated value. When acoustic cavitation occurs, the bubble-assisted enhancement of the initial temperature rise (exposure time t < 2 s) can still be predicted by the theory.     

Numerical simulations of partial elements excitation for hemispherical high-intensity focused ultrasound phased transducer

The hemispherical phased transducer maximizes the coverage of the skull and the ultrasonic energy per unit area of the skull is minimized, thereby reducing the risk of skull burns, but the transducer has a small focal area adjustment range, increasing the focal length of treatment is an urgent question for this type of transducer. In this paper, a three-dimensional high-intensity focused ultrasound (HIFU) transcranial propagation model is established based on the human head structure. The finite difference time domain (FDTD) is combined with the Westervelt acoustic wave nonlinear propagation equation and Penne's biological heat conduction equation for numerical simulation of the sound pressure field and temperature field. Forming a treatable focal area in a small-opening hemispherical transducer with a small amount of numerical simulation calculation focusing at a set position to determine the minimum partial excitation area ratio of focusing. And then, applying these preliminary results to a large-opening diameter hemispherical transducer and the temperature field formed by it or full excitation is studied. The results show that the focus area with the excitation area ratio of less than 22% moves forward to the transducer side when the excitation sound is formed. When the excitation area ratio is greater than or equal to 23%, it focuses at the set position. In the case of partial incentives, using 23% of the partial array, the adjustable range of the treatable focal area formed in the three-dimensional space is larger than that of the full excitation.     

High-speed observation of cavitation bubble cloud structures in the focal region of a 1.2 MHz high-intensity focused ultrasound transducer

Cavitation bubble clouds in the focal region of HIFU play important roles in therapeutic applications of HIFU. Temporal evolution and spatial distribution of cavitation bubble clouds generated in the focal region of a 1.2 MHz single element concave HIFU transducer in water are investigated by high-speed photography. It is found that during the initial 600 micro s insonation cavitation bubble clouds organize to the "screw-like structure" or "cap-like structure". The screw-like structure is characterized by a nearly fixed tip at the geometrical focus of the HIFU transducer, and the cap-like structure is marked by a dent formed in the direction of ultrasound transmission. After 600 micro s, another two structures are recorded - "streamer structure" and "cluster structure". The streamer structure is also featured by a nearly fixed bottom position at the focus, while the cluster structure is distinguished by agglomerations of bubbles around the focus.     

基于电阻抗层析成像的高强度聚焦超声温度监测技术

作为一种对正常组织无损伤且不易引起癌细胞转移的非入侵肿瘤治疗手段,高强度聚焦超声(HIFU)治疗过程中焦域的温度监测是实现剂量精准控制的关键.本文基于生物组织的温度-电阻抗的关系,将电阻抗层析成像(EIT)和HIFU治疗相结合,提出了一种利用组织焦平面的表面电压实现电阻抗重构的检测技术.建立了HIFU治疗和EIT综合系统模型,在考虑组织的声吸收条件下,对三维Helmholtz方程在柱坐标下的声场计算进行了二维简化,并引入Pennes生物热传导方程来计算HIFU焦域的声压和温升分布特性;引入生物组织的温度-电阻抗关系,基于麦克斯韦电磁场理论,建立了具有温度分布HIFU焦域的电流和电压计算模型,利用恒流注入的边界条件实现电场计算,获得焦平面的表面电压分布.在数值计算中,利用实验聚焦换能器参数,模拟了在固定声功率下组织焦域的声场和温度场分布,以及中心和偏心聚焦条件下不同治疗时刻的电导率分布;然后通过对称电极的循环电流注入,计算了组织模型焦平面内的电流密度和电势分布,获得了焦平面圆周分布的表面电极电压;进一步采用修正的牛顿-拉夫逊算法,利用32×32的表面电极电压实现了焦平面内电导率分布的重建.结果表明,基于温度-电阻抗关系的EIT电导率重建技术不但能准确定位HIFU焦域中心,还能恢复HIFU治疗中焦域的温度分布,证明了EIT用于HIFU治疗中温度监测的可行性,为其疗效评估和剂量控制提供了一种无创电阻抗测量和成像新方法.     

The interaction of shockwaves with a vapour bubble in boiling histotripsy: The shock scattering effect

Boiling histotripsy is a High Intensity Focused Ultrasound (HIFU) technique which uses a number of short pulses with high acoustic pressures at the HIFU focus to induce mechanical tissue fractionation. In boiling histotripsy, two different types of acoustic cavitation contribute towards mechanical tissue destruction: a boiling vapour bubble and cavitation clouds. An understanding of the mechanisms underpinning these phenomena and their dynamics is therefore paramount to predicting and controlling the overall size of a lesion produced for a given boiling histotripsy exposure condition. A number of studies have shown the effects of shockwave heating in generating a boiling bubble at the HIFU focus and have studied its dynamics under boiling histotripsy insonation. However, not much is known about the subsequent production of cavitation clouds that form between the HIFU transducer and the boiling bubble. The main objective of the present study is to examine what causes this bubble cluster formation after the generation of a boiling vapour bubble. A numerical simulation of 2D nonlinear wave propagation with the presence of a bubble at the focus of a HIFU field was performed using the k-Wave MATLAB toolbox for time domain ultrasound simulations, which numerically solves the generalised Westervelt equation. The numerical results clearly demonstrate the appearance of the constructive interference of a backscattered shockwave by a bubble with incoming incident shockwaves. This interaction (i.e., the reflected and inverted peak positive phase from the bubble with the incoming incident rarefactional phase) can eventually induce a greater peak negative pressure field compared to that without the bubble at the HIFU focus. In addition, the backscattered peak negative pressure magnitude gradually increased from 17.4 MPa to 31.6 MPa when increasing the bubble size from 0.2 mm to 1.5 mm. The latter value is above the intrinsic cavitation threshold of –28 MPa in soft tissue. Our results suggest that the formation of a cavitation cloud in boiling histotripsy is a threshold effect which primarily depends (a) the size and location of a boiling bubble, and (b) the sum of the incident field and that scattered by a bubble.     

Nonlinear absorption in biological tissue for high intensity focused ultrasound

In recent years the propagation of the high intensity focused ultrasound (HIFU) in biological tissue is an interesting area due to its potential applications in non-invasive treatment of disease. The base principle of these applications is the heat effect generated by ultrasound absorption. In order to control therapeutic efficiency, it is important to evaluate the heat generation in biological tissue irradiated by ultrasound. In his paper, based on the Khokhlov-Zabolotkaya-Kuznetsov (KZK) equation in frequency-domain, the numerical simulations of nonlinear absorption in biological tissues for high intensity focused ultrasound are performed. We find that ultrasound thermal transfer effect will be enhanced with the increasing of initial acoustic intensity due to the high harmonic generation. The concept of extra absorption factor is introduced to describe nonlinear absorption in biological tissue for HIFU. The theoretical results show that the heat deposition induced by the nonlinear theory can be nearly two times as large as that predicated by linear theory. Then, the influence of the diffraction effect on the position of the focus in HIFU is investigated. It is shown that the sound focus moves toward the transducer compared with the geometry focus because of the diffraction of the sound wave. The position of the maximum heat deposition is shifted to the geometry focus with the increase of initial acoustic intensity because the high harmonics are less diffraction. Finally, the temperature in the porcine fat tissue changing with the time is predicated by Pennes' equation and the experimental results verify the nonlinear theoretical prediction.     

HIFU治疗中换能器驱动电功率变化机制及规律*

高强度聚焦超声(HIFU)治疗中的驱动电功率对治疗效率起着非常关键的作用,驱动电功率控制的精准性势必会影响治疗的效率和安全性。前期研究表明：HIFU治疗过程中焦域瞬态物理特性的变化会导致换能器的负载阻抗发生变化,进而影响HIFU驱动电功率,但驱动电功率与焦域瞬态物理特性之间的影响关系及规律尚不明确。该文基于电压、电流传感器、空化检测探头和温度传感器等器件,构建了一种HIFU治疗中驱动电功率实时监测及焦域声空化、温度检测系统。基于该实验研究系统,以离体牛心组织作为HIFU辐照对象,分别研究了HIFU焦域温度变化、声空化及组织损伤与驱动电功率之间的变化关系及规律。研究结果表明：当焦域温度升高时,驱动电功率缓慢上升,驱动电功率与温度变化有良好的相关性;当空化产生时,驱动电功率出现明显的波动;当组织出现损伤时,驱动电功率呈陡然下降的变化。三种情景下,驱动电功率变化有明显区别,这有望为区分HIFU治疗过程中焦域处发生损伤和空化以及实时监测靶组织损伤程度提供一种新的解决方案。     

Low dimensional optimization for in vivo real-time porcine liver motion estimation using ultrasound imaging

This study presents a contribution to the tracking of a moving target during high-intensity focused ultrasound (HIFU) treatment. Indeed, HIFU has proved to be highly efficient in inducing homogeneous and reproducible tumor destruction by thermal coagulation necrosis. However, accurate targeting of human abdominal tumors is difficult to maintain due to the motion induced by breathing. An algorithm is presented to track a region of interest of fixed size in a sequence of images. This algorithm was evaluated on synthetic data and on in vivo sequences of ultrasound liver images acquired using 12 MHz ultrasound imaging probe at a rate of 16 frames/s.The algorithm presented here was derived from the non-linear constant brightness assumption. Since the motion was smooth it was possible to reduce the space of admissible displacements; hence the number of unknown parameters was small compared with the size of the data. The optimal displacement was estimated by a Gauss-Newton method, and the matrix required at each step was assembled by reading the data only once. This algorithm was applied to simulated data, where the true displacement was known and a precise evaluation was possible. The relative error was about 2%. The algorithm was also applied to a video sequence of sonograms acquired during in vivo experiments. These trials were conducted on porcine liver since its size and physiology are similar to humans. Movements were induced by breathing and heart-beating. Two particular frequencies representing breathing (0.26 Hz) and heart beat (1.14 Hz) were identified in the estimated displacement and were correlated with the monitored breathing (0.27 Hz) and electrocardiograms (1.28 Hz). In addition, a region of interest (ROI) modeling the focal zone of a HIFU transducer was tracked along time. Therefore this study provides a mean of determining the location of the targeted region in vivo during HIFU treatments. This can be applied to correct the location of the focal zone accordingly. This method can preferentially be applied to the liver or to any other moving organ.     

球形腔聚焦换能器的非线性声场建模

球形腔聚焦换能器是一种特殊形式的聚焦换能器。为理论证实球形腔聚焦换能器能突破传统超声聚焦在聚焦精度和聚焦增益上的限制,采用Westervelt非线性方程并结合时域有限差分法,建立了球形腔聚焦换能器的非线性声场的数值模型。数值计算了直径为120 mm的0.6 MHz球形腔聚焦换能器的非线性声场,并与传统球壳形聚焦换能器进行了对比。当激励声压为100 kPa时,球形腔聚焦换能器与同尺寸壳形聚焦换能器相比,焦点正声压增益提高约8.5倍,且焦域精度更高,-6 dB聚焦区域在z方向减小约20倍,达到次波长尺度。研究表明球形腔聚焦换能器在高强度聚焦超声精细治疗上具有潜在的应用前景。      

B模式实时成像定量监控超声空化时空行为的研究

提出一种采用B超图像实现高强聚焦超声(HIFU)治疗时声空化的时空量化监控的方法。首先,采用B模式实时成像系统对不同声辐照能量下的HIFU在凝胶仿体中引发的超声空化进行实验监测;接着,利用二维数字图像处理算法消除高强聚焦超声(HIFU)在B超图像中产生的干涉条纹,并在此基础上,对B超成像中观察到的高亮区域的面积变化情况进行量化分析;最后,进一步讨论了驱动声压或脉冲宽度对超声空化产生的高亮区域的生成速度和面积大小的影响。结果显示该方法可以有效去除B超图像中的干涉条纹,并对HIFU引发的空化现象进行实时监测。实验结果还表明辐照声能量的提高将引发更强烈的声空化行为,并且显著缩短HIFU引发的空化泡群的初始生成时间。研究结果对进一步优化HIFU治疗有重要意义。      

自聚焦换能器的声场研究

高强度聚焦超声（HIFU）治疗局部肿瘤是一项无创伤的新技术,有着很好的应用前景,因此对其声场的研究是有实际的价值的。对声场的研究不仅有利于换能器的设计,提高治疗的效果;而且有助声场测量方案的设计,提高对治疗超声剂量的安全保证。本文采用时域有限差分法研究了自聚焦换能器的声场,分别对简谐波,脉冲波进行了研究。比较清楚地看出在焦区的声场可以认为是平面波,这对光纤端面法声场测量提供了有力的支持。     

A derating method for therapeutic applications of high intensity focused ultrasound

Current methods of determining high intensity focused ultrasound (HIFU) fields in tissue rely on extrapolation of measurements in water assuming linear wave propagation both in water and in tissue. Neglecting nonlinear propagation effects in the derating process can result in significant errors. A new method based on scaling the source amplitude is introduced to estimate focal parameters of nonlinear HIFU fields in tissue. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK-type equation and are compared to those simulated for propagation in water. Focal wave-forms, peak pressures, and intensities are calculated over a wide range of source outputs and linear focusing gains. Our modeling indicates, that for the high gain sources which are typically used in therapeutic medical applications, the focal field parameters derated with our method agree well with numerical simulation in tissue. The feasibility of the derating method is demonstrated experimentally in excised bovine liver tissue.     

基于分数导数研究高强度聚焦超声的非线性声场

在高强度聚焦超声(high intensity focused ultrasound, HIFU) 的研究中, 生物组织的衰减和色散性质会对声能量的空间分布产生影响. 本文提出应用分数导数修正非线性Khokhlov-Zabolotskaya-Kuznetsov (KZK)方程, 研究生物组织中非线性HIFU声场. 对三种生物仿体的衰减和声速色散的理论实验研究表明分数导数应用的可行性, 在此基础上通过数值仿真分析研究了衰减及声速随频率的变化对HIFU焦域分布的影响. 研究结果表明, 在计算强非线性聚焦超声时, 由于高次谐波的强色散作用, 引入分数导数来解决生物组织特殊的衰减以及色散问题可进一步提高HIFU治疗的安全性. 关键词： 分数导数 声衰减 色散 高强度聚焦超声     

The Relationship of Cavitation to the Negative Acoustic Pressure Amplitude in Ultrasonic Therapy

The relationship between the cavitation and acoustic peak negative pressure in the high-intensity focused ultrasound(HIFU)Held is analyzed in water and tissue phantom.The peak negative pressure at the focus is determined by a hybrid approach combining the measurement with the simulation.The spheroidal beam equation is utilized to describe the nonlinear acoustic propagation.The waveform at the focus is measured by a fiber optic probe hydrophone in water.The relationship between the source pressure amplitude and the excitation voltage is determined by fitting the measured ratio of the second harmonic to the fundamental component at the focus,based on the model simulation.Then the focal negative pressure is calculated for arbitrary voltage excitation in water and tissue phantom.A portable B-mode ultrasound scanner is applied to monitor HIFU-induced cavitation in real time,and a passive cavitation detection(PCD)system is used to acquire the bubble scattering signals in the HIFU focal volume for the cavitation quantification.The results show that:(1)unstable cavitation starts to appear in degassed water when the peak negative pressure of HIFU signals reaches 13.5 MPa;and(2)the cavitation activity can be detected in tissue phantom by B-mode images and in the PCD system with HIFU peak negative pressures of 9.0 MPa and 7.8 MPa,respectively,which suggests that real-time B-mode images could be used to monitor the cavitation activity in two dimensions,while PCD systems are more sensitive to detect scattering and emission signals from cavitation bubbles.     

正交电磁场中粒子束的质量聚焦及粒子轨迹

<正>交电磁场中粒子的运动轨迹在拐点处按指数规律变化,使不同质量离子的轨迹有明显区别,由此可创建新的电磁核素分离法。从牛顿运动方程出发,基于单粒子轨道法阐述被分离核素在正交电磁场中的运动规律,重点找出轨迹的拐点。给出了多质量粒子束在正交电磁场中的质量聚焦特性,以Li离子为例,应用MATLAB模拟粒子束的运动轨迹,结果表明正交电磁场中可实现多质量束流的质量分离。总结出粒子轨迹方程的特点,为多质量束流分离结构的工程化实现提供参数。研究成果可应用到质量分离器、质谱分析仪及材料提纯等装置的研制中,同时对于特殊位形电磁场控制多质量束流等相关领域的研究亦有一定的参考价值。     

Quantitative estimation of ultrasound beam intensities using infrared thermography-Experimental validation

Infrared (IR) thermography is a technique that has the potential to rapidly and noninvasively determine the intensity fields of ultrasound transducers. In the work described here, IR temperature measurements were made in a tissue phantom sonicated with a high-intensity focused ultrasound (HIFU) transducer, and the intensity fields were determined using a previously published mathematical formulation relating intensity to temperature rise at a tissue/air interface. Intensity fields determined from the IR technique were compared with those derived from hydrophone measurements. Focal intensities and beam widths determined via the IR approach agreed with values derived from hydrophone measurements to within a relative difference of less than 10%, for a transducer with a gain of 30, and about 13% for a transducer with a gain of 60. At axial locations roughly 1 cm in front (pre-focal) and behind (post-focal) the focus, the agreement with hydrophones for the lower-gain transducer remained comparable to that in the focal plane. For the higher-gain transducer, the agreement with hydrophones at the pre-focal and post-focal locations was around 40%.     

A novel method for estimating the focal size of two confocal high-intensity focused ultrasound transducers

Estimating the focal size and position of a high-intensity focused ultrasound (HIFU) transducer remains a challenge since traditional methods, such as hydrophone scanning or schlieren imaging, cannot tolerate high pressures, are directional, or provide low resolution. The difficulties increase when dealing with the complex beam pattern of a multielement HIFU transducer array, e.g., two transducers facing each other. In the present study we show a novel approach to the visualization of the HIFU focus by using shockwave-generated bubbles and a diagnostic B-mode scanner. Bubbles were generated and pushed by shock waves toward the HIFU beam, and were trapped in its pressure valleys. These trapped bubbles moved along the pressure valleys and thereby delineated the shape and size of the HIFU beam. The main and sidelobes of 1.1- and 3.5 MHz HIFU beams were clearly visible, and could be measured with a millimeter resolution. The combined foci could also be visualized by observing the generation of sustained inertial cavitation and enhanced scattering. The results of this study further demonstrate the possibility of reducing the inertial cavitation threshold by the local introduction of shock wave-generated bubbles, which might be useful when bubble generation and cavitation-related bioeffects are intended within a small region in vivo.