Modeling non-spherical oscillations and stability of acoustically driven shelled microbubbles

The oscillation and destruction of microbubbles under ultrasound excitation form the basis of contrast enhanced ultrasound imaging and microbubble assisted drug and gene delivery. A typical microbubble has a size of a few micrometers and consists of a gas core encapsulated by a shell. These bubbles can be driven into surface mode oscillations, which not only contribute to the measured acoustic signal but can lead to bubble destruction. Existing models of surface model oscillations have not considered the effects of a bubble shell. In this study a model was developed to study the surface mode oscillations in shelled bubbles. The effects of shell viscosity and elasticity on the surface mode oscillations were modeled using a Boussinesq-Scriven approach. Simulation was conducted using the model with various bubble sizes and driving acoustic pressures. The occurrence of surface modes and the number of ultrasound cycles needed for the occurrence were calculated. The simulation results show a significant difference between shelled bubbles and shell free bubbles. The shelled bubbles have reduced surface mode amplitudes and a narrower bubble size range within which these modes develop compared to shell free bubbles. The clinical implications were also discussed.     

A method for estimating time-dependent acoustic cross-sections of bubbles and bubble clouds prior to the steady state

Models for the acoustic cross-sections of gas bubbles undergoing steady-state pulsation in liquid have existed for some time. This article presents a theoretical scheme for estimating the cross-sections of single bubbles, and bubble clouds, from the start of insonation onward. In this period the presence of transients can significantly alter the cross-section from the steady-state value. The model combines numerical solutions of the Herring-Keller model with appropriate damping values to calculate the extinction cross-section of a bubble as a function of time in response to a continuous harmonic sound field (it is also shown how the model can be adapted to estimate the time-dependent scatter cross-section). The model is then extended to determine the extinction cross-section area of multiple bubbles of varying population distributions assuming no bubble-bubble interactions. The results have shown that the time taken to reach steady state is dependent on the closeness of the bubble to resonance, and on the driving pressure amplitude. In the response of the population as a whole, the time to reach steady state tends to decrease with increasing values of the driving pressure amplitude; and with the increasing values of the ratio of the numbers of bubbles having radii much larger than resonance to the number of resonant bubbles. The implications of these findings for the use of acoustic pulses are explored.     

Liquid compressibility effects during the collapse of a single cavitating bubble

The effect of liquid compressibility on the dynamics of a single, spherical cavitating bubble is studied. While it is known that compressibility damps the amplitude of bubble rebounds, the extent to which this effect is accurately captured by weakly compressible versions of the Rayleigh-Plesset equation is unclear. To clarify this issue, partial differential equations governing conservation of mass, momentum, and energy are numerically solved both inside the bubble and in the surrounding compressible liquid. Radiated pressure waves originating at the unsteady bubble interface are directly captured. Results obtained with Rayleigh-Plesset type equations accounting for compressibility effects, proposed by Keller and Miksis [J. Acoust. Soc. Am. 68, 628-633 (1980)], Gilmore, and Tomita and Shima [Bull. JSME 20, 1453-1460 (1977)], are compared with those resulting from the full model. For strong collapses, the solution of the latter reveals that an important part of the energy concentrated during the collapse is used to generate an outgoing pressure wave. For the examples considered in this research, peak pressures are larger than those predicted by Rayleigh-Plesset type equations, whereas the amplitudes of the rebounds are smaller.     

Nonlinear oscillation and acoustic scattering of bubbles

The scattered acoustic pressure and scattered cross section of bubbles is studied using the scattered theory of bubbles. The nonlinear oscillations of bubbles and the scattering acoustic fields of a spherical bubble cluster are numerically simulated based on the bubble dynamic and fluid dynamic. The influences of the interaction between bubbles on scattering acoustic field of bubbles are researched. The results of numerical simulation show that the oscillation phases of bubbles are delayed to a certain extent at different positions in the bubble cluster, but the radii of bubbles during oscillation do not differ too much at different positions. Furthermore, directivity of the acoustic scattering of bubbles is obvious. The scattered acoustic pressures of bubbles are different at the different positions inside and outside of the bubble cluster. The scattering acoustic fields of a spherical bubble cluster depend on the driving pressure amplitude, driving frequency, the equilibrium radii of bubbles, bubble number and the radius of the spherical bubble cluster. These theoretical predictions provide a further understanding of physics behind ultrasonic technique and should be useful for guiding ultrasonic application.     

Radial and translational oscillations of an acoustically levitated bubble in aqueous ethanol solutions

The radial and translational oscillations of a single cavitation bubble in a standing ultrasound wave were investigated experimentally at various driving acoustic pressures for aqueous ethanol solutions with different bulk molar fractions of ethanol range of 0-1.3 × 10(-3). The results show that both the lower and upper stability thresholds of the acoustic driving pressure decreased as the concentration of ethanol was increased. At a given driving pressure the ambient and maximum bubble sizes increased with increasing ethanol concentration. In addition, as the ethanol was increased, the sonoluminescence intensity decreased while the bubble dynamics remained largely unchanged. The translational oscillation of the levitated bubble, however, became increasingly violent with increasing ethanol concentration. The displacement of the bubble reached 0.7 mm at the highest concentration studied (1.3 × 10(-3)) and the maximum bubble size was found to change as the bubble jumped up and down. This bubble translation may be responsible for the decrease of the acoustic driving pressure threshold and suggests that repetitive injection of ethanol molecules into the bubble takes place. These results may account for the different sensitivities of single bubble and multi-bubble sonoluminescence to the presence of volatile additives.     

Regimes of bubble volume oscillations in a pipe

The effect of an acoustically driven bubble on the acoustics of a liquid-filled pipe is theoretically analyzed and the dimensionless groups of the problem are identified. The different regimes of bubble volume oscillations are predicted theoretically with these dimensionless groups. Three main regimes can be identified: (1) For small bubbles and weak driving, the effect of the bubble oscillations on the acoustic field can be neglected. (2) For larger bubbles and still small driving, the bubble affects the acoustic field, but due to the small driving, a linear theory is sufficient. (3) For large bubbles and large driving, the two-way coupling between the bubble and the flow dynamics requires the solution of the full nonlinear problem. The developed theory is then applied to an air bubble in a channel of an inkjet printhead. A numerical model is developed to test the predictions of the theoretical analysis. The Rayleigh-Plesset equation is extended to include the influence of the bubble volume oscillations on the acoustic field and vice versa. This modified Rayleigh-Plesset equation is coupled to a channel acoustics calculation and a Navier-Stokes solver for the flow in the nozzle. The numerical simulations indeed confirm the predictions of the theoretical analysis.     

Effect of coupled oscillations on microbubble behavior

Ultrasound contrast agents are encapsulated microbubbles whose nonlinear acoustic scattering signatures have been the foundation of their use in diagnostic imaging. The coupled oscillations of microbubbles along their lines of center are investigated theoretically using radial equations in the monopole approximation and an energy balance, which is obtained for the system. Coupled microbubble pairs of different initial radii are investigated numerically relative to the normal modes for the linearized system. For microbubble pairs of different size bubbles driven below the mode of the smaller bubble and above the mode of the larger bubble, it is shown that oscillations of the smaller agent are affected substantially more by the coupling than those of the larger one. For separation distances of 10 and 500 microns, a difference of approximately 10 dB occurs in the second harmonic output of a 1.0-micron radius agent coupled with a 2.2-micron radius agent forced at 2.0 MHz and 0.3 MPa. The subharmonic spectral peak is shown to decrease approximately 19 dB for the coupling of 1.5- and 2.2-micron radius agents at 10- and 500-micron distances under the same acoustic forcing conditions. These coupling effects on the radiated pressure and its spectral power are highlighted for contrast agent imaging applications.     

Ultrasonic scattering cross sections of shell-encapsulated gas bubbles immersed in a viscoelastic liquid: first and second harmonics

The oscillations of gas bubbles, without shell, immersed in viscoelastic liquids and driven by an acoustic wave have been the subject of several investigations. They demonstrate that the viscosity coefficient and the spring constant of the liquid have significant influence on the scattering cross section of the gas bubble. For shell-encapsulated gas bubbles, the investigations have been concentrated to bubbles immersed in a pure viscous liquid. This present work computes the ultrasonic scattering cross section, first and second harmonics, of shell-encapsulated gas bubbles immersed in a viscoelastic liquid. The theoretical model of the bubble oscillation is based on the generalized Rayleigh-Plesset equation of motion of a spherical cavity immersed in a viscoelastic liquid represented by a three-parameter linear Oldroyd model. The scattering cross section is computed for Albunex type of bubble (shell thickness=15 nm, shell shear viscosity=1.77 Pas, shell modulus of rigidity=88.8 MPa) irradiated by a 3.5 MHz ultrasonic pressure wave with an amplitude of 30 kPa. The results demonstrate that encapsulated bubbles respond independently of the surrounding liquid being pure viscous or viscoelastic as long as the surrounding liquid shear viscosity is as low as 10(-3) Pas. Nevertheless, for higher shear viscosities, the bubble responds differently if the surrounding liquid is pure viscous or viscoelastic. In general, the scattering cross sections of first and second harmonics are larger for the viscoelastic liquid.     

Optimized translation of microbubbles driven by acoustic fields

The problem of a single acoustically driven bubble translating unsteadily in a fluid is considered. The investigation of the translation equation identifies the inverse Reynolds number as a small perturbation parameter. The objective is to obtain a closed-form, leading order solution for the translation of the bubble, assuming nonlinear radial oscillations and a pressure field as the forcing term. In a second part, the periodic attractor of the Rayleigh-Plesset equation serves as basis for an optimal acoustic forcing designed to achieve maximized bubble translation over one dimensionless period. At near-resonant or super-resonant driving frequencies, it seems one cannot improve much on sinusoidal forcing. However at moderate acoustic intensity and sub-resonant frequencies, acoustic wave forms that enhance bubble collapse lead to displacement many times larger than the case of purely sinusoidal forcing. The survey covers a wide spectrum of driving ratios and bubble diameters including those relevant to biomedical applications. Shape stability issues are considered. Together, these results suggest new ways to predict some of the direct and indirect effects of the acoustic radiation force in applications such as targeted drug delivery, selective bubble driving, and accumulation.     

Finite element modeling of acoustic scattering from an encapsulated microbubble near rigid boundary

This article proposes a finite element model (FEM) for predicting the acoustic scattering from an encapsulated microbubble near rigid boundary. The validity of the model is first examined by comparing the acoustic nonlinear response of a free microbubble with that obtained by the Church model. Then this model is used to investigate the effect of the rigid boundary on acoustic scattering signals from microbubble. The results indicate that the resonance frequency decreases while the oscillation amplitude increases as the microbubble approaches the rigid boundary. In addition, the fundamental component of the acoustic scattering signal is enhanced compared with that of the free microbubble.     

The Asymmetric Collapse of Bubbles in Compressible Liquid

The analytical solution ora bubble collapse close to a solid boundary in a compressible water is investigatedby means of a perturbation method to first order in the bubble wall Mach number. It is shown, in this paper, that itis the Rayleigh-Plesset equation for incompressible liquid to zero order solution or similar to the Gilmore equation forcompressible water to first order solution when the effect of solid boundary is negligibly small enough, i.e., sufficientlyfar away from the bubble center.     

气泡线性振动时近海面气泡群的声散射

海洋中的不同成因的气泡群是常见的水下声学目标及声呐混响源,因此对水下气泡群进行声学建模意义重大。利用有效媒质理论描述气泡群内部的相速度及声衰减变化,并考虑到海洋中气泡群往往产生于不同界面附近,进一步利用球面波叠加原理描述海面对气泡群散射声波的再辐射,导出了平海面作用下气泡群声散射截面的一般表达式,建立了其声散射模型,研究了单一尺寸及混合尺寸气泡群的声学特性。数值分析表明,气泡群的谐振频率会随其半径或孔隙率增加而降低;由于海面的存在,气泡群声散射截面会随频率进行周期性变化,且随气泡群远离海面,这一变化逐渐加剧。此外,若气泡的黏滞阻尼项在全部阻尼项中占比较高,气泡群声散射强度会在谐振频率附近存在起伏振荡。该模型可为近海面鱼群、气泡羽流及海底泄漏的甲烷气体的声学建模提供一定的理论基础。     

Procedure for averaging differential cross-sections over the experimental angular resolution

Differential cross-sections for collisions of molecules in the thermal energy range normally oscillate rapidly with angle, the oscillations becoming more rapid with increasing relative kinetic energy. The angular resolution in crossed molecular beam experiments is generally insufficient to resolve these rapid oscillations. A method is proposed for averaging differential cross-sections over small angular ranges without actually evaluating them at many angles. The method permits the calculation of averaged cross-sections, which are much more directly comparable with the experimentally determined ones than those evaluated without averaging. Illustrative calculations are presented for three examples : one for elastic scattering (Ar + Kr) and two for rotationally inelastic scattering (Ar + CsF and Ne + N₂). When the differential cross-section oscillates rapidly, as it does in the first two cases, it requires less computational effort to plot the relatively smoothly varying averaged differential cross-section than to plot the non-averaged cross-section.     

Numerical study of the effect of liquid compressibility on acoustic droplet vaporization

In acoustic droplet vaporization (ADV), a cavitated bubble grows and collapses depending on the pressure amplitude of the acoustic pulse. During the bubble collapse, the surrounding liquid is compressed to high pressure, and liquid compressibility can have a significant impact on bubble behavior and ADV threshold. In this work, a one-dimensional numerical model considering liquid compressibility is presented for ADV of a volatile microdroplet, extending our previous Rayleigh-Plesset based model [Ultrason. Chem. 71 (2021) 105361]. The numerical results for bubble motion and liquid energy change in ADV show that the liquid compressibility highly inhibits bubble growth during bubble collapse and rebound, especially under high acoustic frequency conditions. The liquid compressibility effect on the ADV threshold is quantified with varying acoustic frequencies and amplitudes.     

超声微泡低频动力学特性及其生物效应

理论上利用有耗散函数的Lagrange方程,建立了有壳微泡的R(t)运动方程,开展了自由空间中有壳微泡动力学特性的研究,表明微泡内外半径增量随声压的增大、超声频率的降低、初始内径的增大及壳厚的减薄而迅速增大。实验上,利用Mie散射技术在80°散射角和前向Mie散射检测新技术实验测量了微泡R(t)曲线;利用体视显微镜,实时观察了超声微泡对动物活体微血管损伤,开展了超声微泡生物效应的动物和细胞试验研究。结果表明:(1)超声作用下,微泡引起肿瘤中微血管壁周期性膨胀收缩而发生管壁破裂,形成血栓和微血管栓塞,抑制了肿瘤生长;(2)超声联合微泡可以破坏微血管内皮生长因子(VEGF)和肝癌细胞,可以减少肿瘤血管和癌细胞再生,因此,低频超声联合微泡技术是一种值得探索抑制肿瘤生长的新技术。     

Numerical simulation of bubble dynamics in a Phan-Thien–Tanner liquid: Non-linear shape and size oscillatory response under periodic pressure

We study non-linear bubble oscillations driven by an acoustic pressure with the bubble being immersed in a viscoelastic, Phan-Thien–Tanner liquid. Solution is provided numerically through a method which is based on a finite element discretization of the Navier–Stokes flow equations. The proposed computational approach does not rely on the solution of the simplified Rayleigh–Plesset equation, is not limited in studying only spherically symmetric bubbles and provides coupled solutions for the velocity, stress fields and bubble interface. We present solutions for non-spherical bubbles, with asphericity being addressed by means of Legendre polynomials or associated Legendre functions. A parametric investigation of the bubble dynamical oscillatory response as a function of the fluid rheological properties shows that the amplitude of bubble oscillations drastically increases as liquid elasticity (quantified by the Deborah number) increases or as liquid viscosity decreases (quantified by the Reynolds number). Extensive numerical calculations demonstrate that increasing elasticity and/or viscosity of the surrounding liquid tend to stabilize the shape anisotropy of an initially non-spherical bubble. Results are shown for pressure amplitudes 0.2–2 MPa and Deborah, Reynolds numbers in the intervals of 1–8 and 0.094–1.256, respectively.     

Resonance frequencies of lipid-shelled microbubbles in the regime of nonlinear oscillations

Knowledge of resonant frequencies of contrast microbubbles is important for the optimization of ultrasound contrast imaging and therapeutic techniques. To date, however, there are estimates of resonance frequencies of contrast microbubbles only for the regime of linear oscillation. The present paper proposes an approach for evaluating resonance frequencies of contrast agent microbubbles in the regime of nonlinear oscillation. The approach is based on the calculation of the time-averaged oscillation power of the radial bubble oscillation. The proposed procedure was verified for free bubbles in the frequency range 1-4 MHz and then applied to lipid-shelled microbubbles insonified with a single 20-cycle acoustic pulse at two values of the acoustic pressure amplitude, 100 kPa and 200 kPa, and at four frequencies: 1.5, 2.0, 2.5, and 3.0 MHz. It is shown that, as the acoustic pressure amplitude is increased, the resonance frequency of a lipid-shelled microbubble tends to decrease in comparison with its linear resonance frequency. Analysis of existing shell models reveals that models that treat the lipid shell as a linear viscoelastic solid appear may be challenged to provide the observed tendency in the behavior of the resonance frequency at increasing acoustic pressure. The conclusion is drawn that the further development of shell models could be improved by the consideration of nonlinear rheological laws.     

观测包膜微泡在超声场中的动力学行为

运用长距离显微成像系统与锁相积分拍摄技术相结合的方法, 拍到了单个造影剂微泡在两种不同频率和不同声压下的周期性振动图像. 根据这些图像得到了微泡直径的实验数据, 并分别用Hoff模型和Rayleigh-Plesset模型对数据进行拟合, 并对数据进行了频谱分析. 结果表明:Hoff模型对实验数据的拟合结果优于Rayleigh-Plesset模型的拟合结果; 二次谐波的相对强度随着声压幅度的升高而增大. 关键词： 包膜微泡 锁相积分拍摄方法 频谱