微泡对高强度聚焦超声焦域影响的研究

微泡对高强度聚焦超声(HIFU)治疗具有增效作用,而HIFU治疗中不同声学条件下微泡对HIFU治疗焦域的影响尚不清楚。本文基于声传播方程、Yang-Church气泡运动方程、生物热传导方程、时域有限差分法(FDTD)、龙格-库塔(RK)法数值仿真研究输入功率、激励频率和气泡初始半径对HIFU在含气泡体模中形成焦域的影响,并利用含Sono Vue造影剂的仿组织体模研究进行实验验证。结果表明,增大输入功率、气泡初始半径和升高激励频率均可增大焦域,随着输入功率的增大,焦域形状可能发生变化,而随着激励频率升高和气泡初始半径的增大,焦域会向远离换能器的方向移动。     

声驻波场中空化泡的动力学特性

以水为工作介质, 考虑了液体的可压缩性, 研究了驻波声场中空化泡的运动特性, 模拟了驻波场中各位置处空化泡的运动状态以及相关参数对各位置处空化泡在主Bjerknes力作用下运动方向的影响. 结果表明: 驻波声场中, 空化泡的运动状态分为三个区域, 即在声压波腹附近空化泡做稳态空化, 在偏离波腹处空化泡做瞬态空化, 在声压波节附近, 空化泡在主Bjerknes 力作用下, 一直向声压波节处移动, 显示不发生空化现象; 驻波场中声压幅值增加有利于空化的发生, 但声压幅值增加到一定上限时, 压力波腹区域将排斥空化泡, 并驱赶空化泡向压力波节移动, 不利于空化现象的发生; 当声频率小于初始空化泡的共振频率时, 声频率越高, 由于主Bjerknes 力的作用将有更多的空化泡向声压波节移动, 不利于空化的发生, 尤其是驻波场液面的高度不应是声波波长的1/4; 当声频率一定时, 空化泡初始半径越大越有利于空化现象的发生, 但当空化泡的初始半径超过声频率的共振半径时, 由于主Bjerknes力的作用将有更多的空化泡向声压波节移动, 不利于空化的发生.     

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     

超声场中单气泡的平移和非球形振动

基于摄动理论和广义伯努利方程,推导出单气泡在超声场中径向振动方程、平移方程和气泡形变方程.数值计算这3个方程,可以得到气泡半径、气泡中心的位移和气泡形变随时间的演化图.计算结果表明:当气泡初始半径和驱动声压不变时,气泡中心初始平移速度增大,气泡径向振动几乎不变,但气泡中心位移和形变量增大,气泡非球形振动愈加明显.当初始平移速度比较小时,气泡的R_0-p_a相图中,不稳定区域仅集中在高驱动声压区域.随着气泡中心初始平移速度不断增大,半径和驱动声压均较小的区域开始呈现不稳定性,且整体不稳定空间范围逐渐增大.另外,气泡在声驻波场中不同位置呈现出不同的振动特征.离波腹点越近的气泡,其径向振动幅度越大,但气泡的平移和形变量变化很小,R_0-p_a相图中不稳定性区域平面分数之间的误差小于4%.     

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。     

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     

声场作用下两空化泡相互作用的研究

建立了声场作用下两空化泡泡壁的运动方程,得出了双空化泡的共振频率,振动半径及空化噪声声压．由频率方程,振动半径和声压方程可以看出两气泡的运动情况与单气泡的运动情况有着明显的不同．共振频率,共振振幅及声压与两气泡之间的间距有关．在一定的简化条件下,运用MATLAB语言对共振频率,共振振幅及空化噪声声压进行了数值求解,发现共振频率和共振振幅随空泡间距的增大而增大,空化噪声声压随距离增大先增大后减小． 关键词： 超声 空化 频率 声压     

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.     

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.     

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。     

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。     

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.     

Resonance behaviors of encapsulated microbubbles oscillating nonlinearly with ultrasonic excitation

The resonance behaviors of a few lipid-coated microbubbles acoustically activated in viscoelastic media were comprehensively examined via radius response analysis. The size polydispersity and random spatial distribution of the interacting microbubbles, the rheological properties of the lipid shell and the viscoelasticity of the surrounding medium were considered simultaneously. The obtained radius response curves present a successive occurrence of linear resonances, nonlinear harmonic and sub-harmonic resonances with the acoustic pressure increasing. The microbubble resonance is radius-, pressure- and frequency-dependent. Specifically, the maximum bubble expansion ratio at the main resonance peak increases but the resonant radius decreases as the ultrasound pressure increases, while both of them decrease with the ultrasound frequency increasing. Moreover, compared to an isolated microbubble case, it is found that large microbubbles in close proximity prominently suppress the resonant oscillations while slightly increase the resonant radii for both harmonic and subharmonic resonances, even leading to the disappearance of the subharmonic resonance with the influences increasing to a certain degree. In addition, the results also suggest that both the encapsulating shell and surrounding medium can substantially dampen the harmonic and subharmonic resonances while increase the resonant radii, which seem to be affected by the medium viscoelasticity to a greater degree rather than the shell properties. This work offers valuable insights into the resonance behaviors of microbubbles oscillating in viscoelastic biological media, greatly contributing to further optimizing their biomedical applications.     

Modeling subharmonic response from contrast microbubbles as a function of ambient static pressure

Variation of subharmonic response from contrast microbubbles with ambient pressure is numerically investigated for non-invasive monitoring of organ-level blood pressure. Previously, several contrast microbubbles both in vitro and in vivo registered approximately linear (5-15 dB) subharmonic response reduction with 188 mm Hg change in ambient pressure. In contrast, simulated subharmonic response from a single microbubble is seen here to either increase or decrease with ambient pressure. This is shown using the code BUBBLESIM for encapsulated microbubbles, and then the underlying dynamics is investigated using a free bubble model. The ratio of the excitation frequency to the natural frequency of the bubble is the determining parameter--increasing ambient pressure increases natural frequency thereby changing this ratio. For frequency ratio below a lower critical value, increasing ambient pressure monotonically decreases subharmonic response. Above an upper critical value of the same ratio, increasing ambient pressure increases subharmonic response; in between, the subharmonic variation is non-monotonic. The precise values of frequency ratio for these three different trends depend on bubble radius and excitation amplitude. The modeled increase or decrease of subharmonic with ambient pressure, when one happens, is approximately linear only for certain range of excitation levels. Possible reasons for discrepancies between model and previous experiments are discussed.     

多层膜磁性微泡的非线性声振动特性

超顺磁性氧化铁纳米粒子与造影剂微泡结合形成磁性微泡,用于产生多模态造影剂,以增强医学超声和磁共振成像.将装载有纳米磁性颗粒的微泡包膜层看作由磁流体膜与磷脂膜组合而成的双层膜结构,同时考虑磁性纳米颗粒体积分数a对膜密度及黏度的影响,从气泡动力学基本理论出发,构建多层膜结构磁性微泡非线性动力学方程.数值分析了驱动声压和频率等声场参数、颗粒体积分数、膜层厚度以及表面张力等膜壳参数对微泡声动力学行为的影响.结果表明,当磁性颗粒体积分数较小且a≤0.1时,磁性微泡声响应特性与普通包膜微泡相似,微泡的声频响应与其初始尺寸和驱动压有关;当驱动声场频率f为磁性微泡共振频率f0的2倍(f=2f0)时,微泡振动失稳临界声压最低;磁性颗粒的存在抑制了泡的膨胀和收缩但抑制效果非常有限;磁性微泡外膜层材料的表面张力参数K及膜层厚度d也会影响微泡的振动,当表面张力参数及膜厚取值分别为0.2—0.4 N/m及50—150 nm时,可观察到气泡存在不稳定振动响应区.     

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.     

Modeling of high-intensity focused ultrasound-induced lesions in the presence of cavitation bubbles

The classical "Bio Heat Transfer Equation (BHTE)" model is adapted to take into account the effects of oscillating microbubbles that occur naturally in the tissue during high-intensity focused ultrasound (HIFU) treatment. First, the Gilmore-Akulichev model is used to quantify the acoustic pressure scattered by microbubbles submitted to HIFU. Because this scattered pressure is not monochromatic, the concept of harmonic attenuation is introduced and a global attenuation coefficient is estimated for bubble-filled tissues. The first results show that this global attenuation coefficient varies significantly with respect to several parameters such as the frequency and the density of microbubbles in the medium, but also with respect to the incident acoustic pressure which thus becomes a transcendental function. Under these conditions, a layer-by-layer modeling, in the direction of propagation, is proposed to calculate the ultrasonic beam. Finally, the BHTE is solved and the HIFU-induced lesions are estimated by the calculation of the thermal dose. Using this model, it can be observed first that, when the firing power increases, the lesion develops clearly in the direction of the transducer, with a shape agreeing with in vivo experimentation. Next, it is observed that the lesion can be significantly modified in size and position, if an interface (skin or inner wall) is simulated as a zone with multiple cavitation nuclei. With a firing power increase, it is also shown how a secondary lesion can appear at the interface and how, beyond a certain threshold, this lesion develops at the main lesion expense. Finally, a better in-depth homogeneity of lesions is observed when the acoustic frequency of HIFU is increased.