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。     

声场中球形空化云中气泡的耦合谐振

本文从泡群中气泡动力学方程出发,对泡壁运动方程进行线性约化,得到球状泡群中气泡谐振频率的表达式,并给出了泡群中气泡谐振频率与单泡Minnaert频率的修正系数.讨论了泡群中气泡初始半径、气泡数量、气泡之间距离对谐振频率的影响.研究结果表明:考虑到气泡的相互作用后,球状泡群中气泡的谐振频率明显小于单泡的Minnaert频率.随着泡群中气泡数量的减少、气泡之间距离增大,泡群中气泡之间的相互作用减弱,气泡的谐振频率回归到Minnaert单泡谐振频率.同时泡群中气泡的谐振频率随气泡之间距离、气泡数量的影响变化梯度也不相同.泡群中气泡数量越多、气泡距离近越近,气泡之间相互作用强,谐振频率变化幅度快.     

超声波声孔效应中气泡动力学的研究

在超声快速制取组织细胞病理切片的过程中，发现激励信号对切片制取效果有明显的影响.为了掌握超声激励信号对组织细胞的影响规律，达到快速制取病理切片的最佳状态，从气泡空化模型入手，通过改变激励信号频率、声压、气泡初始半径和液体黏滞系数等参量，研究了声孔效应中气泡动力学激励机制.数值计算表明：空化泡振动随激励声压增强而升高，随液体黏滞系数增强而减弱；一定频率范围内空化泡振动能保持在膨胀、收缩和振荡的稳定空化状态，存在空化泡稳态振动的最佳激励频率；一定初始半径能保证空化泡产生稳定的振动，存在空化泡稳态振动幅度最大的初始半径.实际操作中，在频率、声压、初始半径和黏滞系数综合作用的若干空化阈内，声孔效应使超声快速法制取细胞组织切片获得最佳效果. 关键词： 声孔效应 超声空化 气泡振动 稳态空化域     

单泡声致发光中气泡运动特性的Mie散射测量

运用光学Mie散射测量,实验研究了声致发光单泡的运动状态和发光光强受激励声场频率f及声压Pa变化的影响,结合动力学R-P方程拟合得到不同声压Pa下气泡半径随时间变化的动力学特征曲线——R(t)曲线,定量确定了气泡平衡半径Ro和压缩比Rmax/Ro,并通过气泡振子模型给出的势能方程估算了气泡塌缩阶段的能量损耗。结果表明:适当控制谐振频率(△f/fo-10-4,fo=21 kHz)和声压(1.2 atm-1.5 atm)可实现稳定的单泡声致发光;并且随着Pa的增大,气泡压缩比增大,回弹势能占总能量的比值逐渐减小(10-1-10-3),气泡在膨胀相聚集的大部分声能很可能以激波和热能形式释放。     

超声场下刚性界面附近溃灭空化气泡的速度分析

为了揭示刚性界面附近气泡空化参数与微射流的相互关系, 从两气泡控制方程出发, 利用镜像原理, 建立了考虑刚性壁面作用的空化泡动力学模型. 数值对比了刚性界面与自由界面下气泡的运动特性, 并分析了气泡初始半径、气泡到固壁面的距离、声压幅值和超声频率对气泡溃灭的影响. 在此基础上, 建立了气泡溃灭速度和微射流的相互关系. 结果表明: 刚性界面对气泡振动主要起到抑制作用; 气泡溃灭的剧烈程度随气泡初始半径和超声频率的增加而降低, 随着气泡到固壁面距离的增加而增加; 声压幅值存在最优值, 固壁面附近的气泡在该最优值下气泡溃灭最为剧烈; 通过研究气泡溃灭速度和微射流的关系发现, 调节气泡溃灭速度可以达到间接控制微射流的目的.     

超声波作用下泡群的共振声响应

从球状泡群气泡动力学方程出发, 考虑泡群间次级声辐射的影响, 得到了声场中两泡群共同存在时气泡振动的动力学方程, 并以此为基础探讨声波驱动下双泡群振动系统的共振响应特征. 由于泡群间气泡间的相互作用, 系统存在低频共振和高频共振现象, 两不同共振频率的数值与泡群内气泡的本征频率相关. 泡群内气泡的本征频率又受到初始半径、泡群大小和泡群内气泡数量的影响. 气泡自由振动和驱动声波的耦合激起泡群内气泡的受迫振动, 气泡初始半径、气泡数密度和驱动声波频率等都会影响泡群内气泡的振动幅值和初相位. 关键词： 气泡群 共振 声响应 超声空化     

低频超声空化场中柱状泡群内气泡的声响应

本文在气泡群振动模型的基础上,考虑气泡间耦合振动的影响,得到了均匀柱状泡群内振动气泡的动力学方程,以此为基础分析了低频超声空化场中柱形气泡聚集区内气泡的非线性声响应特征.气泡间的耦合振动增加了系统对每个气泡的约束,降低了气泡的自然频率,增强了气泡的非线性声响应.随着气泡数密度的增加,气泡的自然共振频率降低,受迫振动气泡受到的抑制增强.数值分析结果表明:1)驱动声波频率越低,气泡的初始半径越小,气泡数密度变化对气泡最大半径变化幅度的影响越大;2)气泡振动幅值响应存在不稳定区,不稳定区域分布与气泡初始半径、驱动声波压力幅值、驱动声波频率等因素有关.在低频超声波作用下,对初始半径处在1—10μm之间的空化气泡而言,气泡初始半径越小,气泡最大半径不稳定区分布范围越大,表明小气泡具有更强的非线性特征.因此,气泡初始半径越小,声环境变化对空化泡声响应稳定性影响越显著.     

考虑水蒸气蒸发和冷凝的球状泡群中泡的动力学特性

为了深入探究空化泡群中气泡的动力学特性,建立了超声驱动下考虑水蒸气的蒸发和冷凝的泡群中泡的动力方程.基于该方程,研究了泡群中泡的位置、泡的数量、泡的初始半径对其动力学特性的影响,探究了超声作用下球状泡群中气泡半径、能量、温度、压力和气泡内水蒸气分子数的变化规律.结果表明:泡群中泡的运动受到周围气泡的抑制作用;泡群中泡的初始半径大小对泡群中泡的半径、能量、温度、压力和气泡内水蒸气分子数有显著影响;泡群中泡的位置距离泡群中心越远,泡的膨胀半径越大;随着泡群中泡的数目增加,泡的振幅减小;超声频率增加,泡群中泡的空化效应减弱;超声声压增加,泡群中泡的空化效应增加.研究结果为超声空化泡群的研究提供了理论参考.     

调频超声脉冲驱动微气泡运动偏移的研究

提出调频超声辐射力技术驱动微泡群,以加强微泡的吸附效率.基于改进的RP方程及粒子轨迹方程研究了微泡群整体的运动位移与调频信号的中心频率、调频范围、信号声压,以及微泡半径分布关系.研究结果表明调频信号在驱动半径具有宽泛分布的气泡群,以及半径分布远离谐振半径的气泡群时,作用效果好于传统正弦波信号.例如中心频率1 MHz、调频范围0.75 MHz的调频脉冲作用高斯分布（平均半径3.5 μm、均方差为1）的微泡群200 μs,可比同等声压的正弦波多约12%的微气泡产生位移30 μm. 关键词： 超声辐射力 调频波 高斯分布     

基于换能器驱动信号特征的高强度聚焦超声焦域损伤实时监测

高强度聚焦超声(high intensity focused ultrasound,HIFU)焦域的实时监测是聚焦超声临床治疗面临的关键问题,目前临床常采用B超图像强回声的变化实现焦域组织损伤的监测,而B超图像出现的强回声大多与焦域处的空化及沸腾气泡相关,无法准确、实时地监测治疗状态.HIFU治疗中焦域组织会伴随温度升高、空化、沸腾和组织特性等变化,换能器表面的声学负载也在不断变化,针对该问题,本文构建了换能器电压电流实时检测平台,通过测量换能器电学参数来感知焦域组织的状态变化.以离体牛肝组织作为HIFU辐照对象,并将相位差变化的结果与离体牛肝组织损伤的结果进行了对照,实验结果表明,在HIFU辐照过程中,换能器电压与电流的相位会出现由相对平稳到大幅波动的过程,此时停止辐照可见焦域出现明显损伤,而此时B超图像灰度无明显变化;此外,当焦域出现空化时,其波动幅度与范围将较之更大.此方法可为HIFU焦域组织损伤监测提供一种新的研究方案和手段.     

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。      

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.     

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.     

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。     

Control of the dynamics of a boiling vapour bubble using pressure-modulated high intensity focused ultrasound without the shock scattering effect: A first proof-of-concept study

Boiling histotripsy is a promising High-Intensity Focused Ultrasound (HIFU) technique that can be used to induce mechanical tissue fractionation at the HIFU focus via cavitation. Two different types of cavitation produced during boiling histotripsy exposure can contribute towards mechanical tissue destruction: (1) a boiling vapour bubble at the HIFU focus and (2) cavitation clouds in between the boiling bubble and the HIFU source. Control of the extent and degree of mechanical damage produced by boiling histotripsy is necessary when treating a solid tumour adjacent to normal tissue or major blood vessels. This is, however, difficult to achieve with boiling histotripsy due to the stochastic formation of the shock scattering-induced inertial cavitation clouds. In the present study, a new histotripsy method termed pressure-modulated shockwave histotripsy is proposed as an alternative to or in addition to boiling histotripsy without inducing the shock scattering effect. The proposed concept is (a) to generate a boiling vapour bubble via localised shockwave heating and (b) subsequently control its extent and lifetime through manipulating peak pressure magnitudes and a HIFU pulse length. To demonstrate the feasibility of the proposed method, bubble dynamics induced at the HIFU focus in an optically transparent liver tissue phantom were investigated using a high speed camera and a passive cavitation detection systems under a single 10, 50 or 100 ms-long 2, 3.5 or 5 MHz pressure-modulated HIFU pulse with varying peak positive and negative pressure amplitudes from 5 to 89 MPa and −3.7 to −14.6 MPa at the focus. Furthermore, a numerical simulation of 2D nonlinear wave propagation with the presence of a boiling bubble at the focus of a HIFU field was conducted by numerically solving the generalised Westervelt equation. The high speed camera experimental results showed that, with the proposed pressure-modulated shockwave histotripsy, boiling bubbles generated by shockwave heating merged together, forming a larger bubble (of the order of a few hundred micron) at the HIFU focus. This coalesced boiling bubble then persisted and maintained within the HIFU focal zone until the end of the exposure (10, 50, or 100 ms). Furthermore, and most importantly, no violent cavitation clouds which typically appear in boiling histotripsy occurred during the proposed histotripsy excitation (i.e. no shock scattering effect). This was likely because that the peak negative pressure magnitude of the backscattered acoustic field by the boiling bubble was below the cavitation cloud intrinsic threshold. The size of the coalesced boiling bubble gradually increased with the peak pressure magnitudes. In addition, with the proposed method, an oval shaped lesion with a length of 0.6 mm and a width of 0.1 mm appeared at the HIFU focus in the tissue phantom, whereas a larger lesion in the form of a tadpole (length: 2.7 mm, width: 0.3 mm) was produced by boiling histotripsy. Taken together, these results suggest that the proposed pressure-modulated shockwave histotripsy could potentially be used to induce a more spatially localised tissue destruction with a desired degree of mechanical damage through controlling the size and lifetime of a boiling bubble without the shock scattering effect.     

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。     

声场中双空化泡的运动特性

空化泡的运动特性是声场作用下的动力学行为,受空化泡初始半径,声压幅值,驱动声压频率,液体特性等众多因素的影响,是个复杂工程。本文从双空化泡运动方程出发,考虑到液体粘滞系数、空化泡辐射阻尼项的影响,研究了不同初始半径、驱动声压频率、驱动声压幅值、液体粘滞系数下空化泡泡壁的运动情况,研究结果表明不同初始半径、外界驱动声压频率、驱动声压幅值、液体粘滞系数均会对空化泡的膨胀比和空化泡的溃灭时间有一定影响。     

Difference frequency and its harmonic emitted by microbubbles under dual frequency excitation

Vibro-acoustography is an elasticity imaging method that uses two ultrasound beams of slightly different frequency to excite an object and detects the resulting acoustic emission (AE) at the difference frequency. This method is especially sensitive to bubbles due to their nonlinearity. This study explores the harmonic acoustic emission (HAE) at twice the difference frequency emitted from bubbles. A perturbation method based on the dynamic bubble equation is used to derive the AE and HAE from a single bubble excited by dual frequency waves. Simulation shows that HAE is generated only by microbubbles whose resonant frequencies match the incident ultrasound frequencies. In contrast, AE is more sensitive to resonance at the difference frequency, which is relevant to sub-millimeter bubbles. This finding was confirmed by experiments where HAE was produced from Optison microbubbles, but not from larger air bubbles which are off resonance at the incident ultrasound frequency. In conclusion, harmonic acoustic emission is present for microbubbles. It is very sensitive to the size of the bubble and may be used for selective detection of microbubbles.