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.     

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.     

High-speed observation of cavitation bubble clouds near a tissue boundary in high-intensity focused ultrasound fields

Cavitation bubble clouds generated near a tissue boundary by high-intensity focused ultrasound (HIFU) were studied using high-speed photography. In all, 171 image series were captured during the initial 100 ms of continuous HIFU exposure, which showed that cavitation bubble clouds at the tissue boundary organized into two structures - “cone-shape bubble cloud structure” recorded in 146 image series and “crown-shape bubble cloud structure” recorded in 18 image series. The remaining 7 image series showed the interchanging of these two structures. It was found that when cavitation bubbles first appeared at the tissue boundary, they developed to cone-shape bubble cloud. The cone-shape bubble cloud structure was characterized by a nearly fixed tip in front of the tissue boundary. When the cavitation bubbles initially appeared away from the tissue boundary they evolved into a crown-shape bubble cloud. Deformation of tissue boundary was shown in all the recorded image series.     

Luminescence induced by spherically focused acoustic pulses in liquids

The determination of the phase of the bubble oscillation at the instant of light emission, which is a key issue for understanding the origin of cavitation luminescence of liquids, is discussed. The observation of luminescence in the course of the nucleation and growth of a bubble up to its collapse is performed in a bipolar wave consisting of a compression phase followed by a rarefaction phase in the regime of a two-fraction bubble cluster formation. The space-time distributions of the luminescence intensity and pressure and the dynamics of the cluster in water and a glycerin solution are investigated at the early stage of cavitation. A correlation between the maximal density of light flashes and the positive pressure pulses in the field of superposition of the initial and secondary cavitation compression waves is revealed. It is shown that the spherical focusing of acoustic pulses both away from the boundaries of the liquid and near its free surface makes it possible to compare the luminescence intensities for different rates of the pressure decrease.     

Bubble proliferation in the cavitation field of a shock wave lithotripter

Lithotripter shock waves (SWs) generated in non-degassed water at 0.5 and 2 Hz pulse repetition frequency (PRF) were characterized using a fiber-optic hydrophone. High-speed imaging captured the inertial growth-collapse-rebound cycle of cavitation bubbles, and continuous recording with a 60 fps camcorder was used to track bubble proliferation over successive SWs. Microbubbles that seeded the generation of bubble clouds formed by the breakup of cavitation jets and by bubble collapse following rebound. Microbubbles that persisted long enough served as cavitation nuclei for subsequent SWs, as such bubble clouds were enhanced at fast PRF. Visual tracking suggests that bubble clouds can originate from single bubbles.     

Physical investigation of acoustic waves induced by the oscillation and collapse of the single bubble

The objective of this paper is to apply both experimental and numerical methods to investigate acoustic waves induced by the oscillation and collapse of a single bubble. In the experiments, the schlieren technique is used to capture the temporal evolution of the bubble shapes, and the corresponding acoustic waves. The results are presented for the single bubble generated by a low-voltage bubble generator in the free field of water. During the numerical simulations, a three-dimensional (3D) weakly compressible model is introduced to investigate the single bubble dynamics, including the generation and propagation of acoustic waves. The results show that (1) Compression wave, rarefaction wave and shock wave are generated during expansion stage, collapse stage and rebound stage of the bubble respectively. (2) Compression waves are induced by the rapid expansion of the bubble and eventually steepen into one shock wave propagating outward in the liquid, then another strong shock wave is emitted at the final collapse stage. The velocity and pressure of the liquid field increases after the shock wave. (3) Rarefaction waves are generated during the collapse stage due to the contraction of the bubble. The rarefaction wave reduces the liquid pressure and its spatial distribution is dispersive. The pressure of these acoustic waves and their effect on the liquid velocity attenuate with the increase of propagation distance.     

水下强声波脉冲负压的产生和空化气泡运动

首先利用高速摄影和压力传感器测量的方法, 对曲面反射式水下强声波脉冲的传播和聚焦过程进行了实验研究.实验研究发现, 椭球面反射罩在起到汇聚声能的作用的同时也将使得强声波脉冲在传播过程中形成负压区, 并由此而引发近场声传播通道上空化气泡群的产生. 在实验结果的基础上, 进一步利用基于Kirchhoff衍射定理的声传播模型和大振幅条件下的QX气泡运动方程, 对强声波脉冲负压区的形成原因及空化气泡的运动过程进行了数值计算和分析. 研究结果表明, 在焦前区, 源于反射罩内表面的"尾波"和出口处的"边缘波"在传播过程中将形成反射波中的负压区; 在焦后区, 源于反射罩顶点的"中心波"在传播过程中将形成反射波中的负压区. 在反射波作用下, 空化气泡体现出了"正压区受压缩并振荡, 负压区膨胀"的运动特点. 在反射波之后, 空化气泡将出现成长、坍缩和回弹等典型的物理过程. 研究结果对曲面反射式水下强声波传播物理规律的认识具有实际意义.     

Effects of acoustic parameters on bubble cloud dynamics in ultrasound tissue erosion (histotripsy)

High intensity pulsed ultrasound can produce significant mechanical tissue fractionation with sharp boundaries ("histotripsy"). At a tissue-fluid interface, histotripsy produces clearly demarcated tissue erosion and the erosion efficiency depends on pulse parameters. Acoustic cavitation is believed to be the primary mechanism for the histotripsy process. To investigate the physical basis of the dependence of tissue erosion on pulse parameters, an optical method was used to monitor the effects of pulse parameters on the cavitating bubble cloud generated by histotripsy pulses at a tissue-water interface. The pulse parameters studied include pulse duration, peak rarefactional pressure, and pulse repetition frequency (PRF). Results show that the duration of growth and collapse (collapse cycle) of the bubble cloud increased with increasing pulse duration, peak rarefactional pressure, and PRF when the next pulse arrived after the collapse of the previous bubble cloud. When the PRF was too high such that the next pulse arrived before the collapse of the previous bubble cloud, only a portion of histotripsy pulses could effectively create and collapse the bubble cloud. The collapse cycle of the bubble cloud also increased with increasing gas concentration. These results may explain previous in vitro results on effects of pulse parameters on tissue erosion.     

Modified shock waves for extracorporeal shock wave lithotripsy: a simulation based on the Gilmore formulation

Extracorporeal shock wave lithotripsy (SWL) is a reliable therapy for the treatment of urolithiasis. Nevertheless, improvements to enhance stone fragmentation and reduce tissue damage are still needed. During SWL, cavitation is one of the most important stone fragmentation mechanisms. Bubbles with a diameter between about 7 and 55 μm have been reported to expand and collapse after shock wave passage, forming liquid microjets at velocities of up to 400 m/s that contribute to the pulverization of renal calculi. Several authors have reported that the fragmentation efficiency may be improved by using tandem shock waves. Tandem SWL is based on the fact that the collapse of a bubble can be intensified if a second shock wave arrives tenths or even a few hundredths of microseconds before its collapse. The object of this study is to determine if tandem pulses consisting of a conventional shock wave (estimated rise time between 1 and 20 ns), followed by a slower second pressure profile (0.8 μs rise time), have advantages over conventional tandem SWL. The Gilmore equation was used to simulate the influence of the modified pressure field on the dynamics of a single bubble immersed in water and compare the results with the behavior of the same bubble subjected to tandem shock waves. The influence of the delay between pulses on the dynamics of the collapsing bubble was also studied for both conventional and modified tandem waves. For a bubble of 0.07 mm, our results indicate that the modified pressure profile enhances cavitation compared to conventional tandem waves at a wide range of delays (10-280 μs). According to this, the proposed pressure profile could be more efficient for SWL than conventional tandem shock waves. Similar results were obtained for a ten times smaller bubble.     

水下等离子体声源的冲击波负压特性

基于修正的Rayleigh气泡脉动方程对水下等离子体声源放电产生的 强声冲击波的传播过程进行了分析; 利用Euler方程作为控制方程组, 建立了水下等离子体声源的聚束声场模型, 通过仿真计算获得的传播云图对冲击波负压的形成机理进行了直观的理论分析. 结果表明: 经过聚能反射罩反射汇聚得到的聚束波在反射稀疏波和水的惯性作用下, 聚束波周围水域产生了拉伸, 形成负压区, 如果拉伸力大于水的抗拉上限, 就会使得水中形成不连续现象, 即出现空化气泡; 此外聚能罩边缘处产生的衍射波进一步加剧了负压的产生, 边缘衍射波最终与拉伸波叠加, 使冲击波负压达到最大值; 通过对比仿真波形和实验波形, 从而验证和进一步揭示了冲击波负压的形成原因. 研究结果对认识水下冲击波的传播规律和进一步改进等离子体声源的设计具有指导意义. 关键词： 等离子体声源 冲击波负压 聚束声场模型 气泡     

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.     

Spatial-temporal dynamics of cavitation bubble clouds in 1.2 MHz focused ultrasound field

Cavitation bubbles have been recognized as being essential to many applications of ultrasound. Temporal evolution and spatial distribution of cavitation bubble clouds induced by a focused ultrasound transducer of 1.2 MHz center frequency are investigated by high-speed photography. It is revealed that at a total acoustic power of 72 W the cavitation bubble cloud first emerges in the focal region where cavitation bubbles are observed to generate, grow, merge and collapse during the initial 600 μs. The bubble cloud then grows upward to the post-focal region, and finally becomes visible in the pre-focal region. The structure of the final bubble cloud is characterized by regional distribution of cavitation bubbles in the ultrasound field. The cavitation bubble cloud structure remains stable when the acoustic power is increased from 25 W to 107 W, but it changes to a more violent form when the acoustic power is further increased to 175 W.     

Modification of the ultrasound induced activity by the presence of an electrode in a sonoreactor working at two low frequencies (20 and 40 kHz). Part I: Active zone visualization by laser tomography

Sonoelectrochemical experiments differ from sonochemical ones by the introduction of electrodes in the sonicated reaction vessel. The aim of the study is to characterize the changes of the ultrasonic activity induced by the presence of an electrode located in front of the transducer. The scope of our investigations concerns two low frequencies vibration modes: 20 and 40 kHz. For this purpose, two laser visualization techniques have been used. The first part of the study, described in the present paper (part I), deals with the laser tomography technique which provides an accurate picture of the reactor actives zones, related to numerous cavitation events. For each frequency, two parameters were studied: the electrical power supplied to the transducer and the electrode transducer distance. At both frequencies, without electrode, we can observe distinct zones corresponding to cavitation production and stationary waves establishment. When increasing the input power, bubble clouds tend to form a unique cloud near the transducer. In presence of the electrode, bubble cavitation clouds are largely influenced by the obstacle. The second part of the paper (part II) will describe the Particle Image Velocimetry (P.I.V.) technique which allows to measure the velocity vector field in the fluid portion between the horn and the electrode.     

Deformation of a bubble formed by coalescence of cavitation inclusions and shock wave inside it at strong expansion and compression

Dynamics of a cavitation bubble is considered at its strong expansion and subsequent compression. The bubble is formed by merging of two identical spherical cavitation microcavities in the pressure antinode of the intensive ultrasonic standing wave in the half-wave phase with negative pressure. Deformations of bubble and deformations of radially converging shock waves occurring therein at bubble compression are studied depending on the size of microcavities forming the bubble. It is found that compression of the medium in the bubble by the converging shock wave is kept close to the spherical one only in the case, when the radius of merging microcavities is 1800 times smaller than the radius of the bubble formed by merging at the time of its maximal expansion.     

空化单气泡外围压强分布

关键词：     

Optical and acoustic monitoring of bubble cloud dynamics at a tissue-fluid interface in ultrasound tissue erosion

Short, high-intensity ultrasound pulses have the ability to achieve localized, clearly demarcated erosion in soft tissue at a tissue-fluid interface. The primary mechanism for ultrasound tissue erosion is believed to be acoustic cavitation. To monitor the cavitating bubble cloud generated at a tissue-fluid interface, an optical attenuation method was used to record the intensity loss of transmitted light through bubbles. Optical attenuation was only detected when a bubble cloud was seen using high speed imaging. The light attenuation signals correlated well with a temporally changing acoustic backscatter which is an excellent indicator for tissue erosion. This correlation provides additional evidence that the cavitating bubble cloud is essential for ultrasound tissue erosion. The bubble cloud collapse cycle and bubble dissolution time were studied using the optical attenuation signals. The collapse cycle of the bubble cloud generated by a high intensity ultrasound pulse of 4-14 micros was approximately 40-300 micros depending on the acoustic parameters. The dissolution time of the residual bubbles was tens of ms long. This study of bubble dynamics may provide further insight into previous ultrasound tissue erosion results.     

Modeling of interaction between therapeutic ultrasound propagation and cavitation bubbles

In medical applications of high intense focused ultrasound the mechanism of interaction between ultrasound waves and cavitation bubbles is responsible for several therapeutic effects as well as for undesired side effects. Based on a two-phase continuum approach for bubbly liquids, in this paper a numerical model is presented to simulate these interactions. The numerical results demonstrate the influence of the cavitation bubble cloud on ultrasound propagation. In the case of a lithotripter pulse an increased bubble density leads to significant changes in the tensile part of the pressure waveform. The calculations are verified by measurements with a fiber optical hydrophone and by experimental results of the bubble cloud dynamics.     

On the governing fragmentation mechanism of primary intermetallics by induced cavitation

One of the main applications of ultrasonic melt treatment is the grain refinement of aluminium alloys. Among several suggested mechanisms, the fragmentation of primary intermetallics by acoustic cavitation is regarded as very efficient. However, the physical process causing this fragmentation has received little attention and is not yet well understood. In this study, we evaluate the mechanical properties of primary Al₃Zr intermetallics by nano-indentation experiments and correlate those with in-situ high-speed imaging (of up to 1 Mfps) of their fragmentation process by laser-induced cavitation (single bubble) and by acoustic cavitation (cloud of bubbles) in water. Intermetallic crystals were chemically extracted from an Al-3 wt% Zr alloy matrix. Mechanical properties such as hardness, elastic modulus and fracture toughness of the extracted intermetallics were determined using a geometrically fixed Berkovich nano-diamond and cube corner indenter, under ambient temperature conditions. The studied crystals were then exposed to the two cavitation conditions mentioned. Results demonstrated for the first time that the governing fragmentation mechanism of the studied intermetallics was due to the emitted shock waves from the collapsing bubbles. The fragmentation caused by a single bubble collapse was found to be almost instantaneous. On the other hand, sono-fragmentation studies revealed that the intermetallic crystal initially underwent low cycle fatigue loading, followed by catastrophic brittle failure due to propagating shock waves. The observed fragmentation mechanism was supported by fracture mechanics and pressure measurements using a calibrated fibre optic hydrophone. Results showed that the acoustic pressures produced from shock wave emissions in the case of a single bubble collapse, and responsible for instantaneous fragmentation of the intermetallics, were in the range of 20–40 MPa. Whereas, the shock pressure generated from the acoustic cavitation cloud collapses surged up to 1.6 MPa inducing fatigue stresses within the crystal leading to eventual fragmentation.     

Cavitation bubble behavior and bubble–shock wave interaction near a gelatin surface as a study of in vivo bubble dynamics

The collapse of a single cavitation bubble near a gelatin surface, and the interaction of an air bubble attached to a gelatin surface with a shock wave, were investigated. These events permitted the study of the behavior of in vivo cavitation bubbles and the subsequent tissue damage mechanism during intraocular surgery, intracorporeal and extracorporeal shock wave lithotripsy. Results were obtained with high-speed framing photography. The cavitation bubbles near the gelatin surface did not produce significant liquid jets directed at the surface, and tended to migrate away from it. The period of the motion of a cavitation bubble near the gelatin surface was longer than that of twice the Rayleigh's collapse time for a wide range of relative distance, L/R_max, excepting for very small L/R_max values (L was the stand-off distance between the gelatin surface and the laser focus position, and R_max was the maximum bubble radius). The interaction of an air bubble with a shock wave yielded a liquid jet inside the bubble, penetrating into the gelatin surface. The liquid jet had the potential to damage the gelatin. The results predicted that cavitation-bubble-induced tissue damage was closely related to the oscillatory bubble motion, the subsequent mechanical tissue displacement, and the liquid jet penetration generated by the interaction of the remaining gas bubbles with subsequent shock waves. The characteristic bubble motion and liquid jet formation depended on the tissue's mechanical properties, resulting in different damage mechanisms from those observed on hard materials.     

A simple model of ultrasound propagation in a cavitating liquid. Part II: Primary Bjerknes force and bubble structures

In a companion paper, a reduced model for propagation of acoustic waves in a cloud of inertial cavitation bubbles was proposed. The wave attenuation was calculated directly from the energy dissipated by a single bubble, the latter being estimated directly from the fully nonlinear radial dynamics. The use of this model in a mono-dimensional configuration has shown that the attenuation near the vibrating emitter was much higher than predictions obtained from linear theory, and that this strong attenuation creates a large traveling wave contribution, even for closed domain where standing waves are normally expected. In this paper, we show that, owing to the appearance of traveling waves, the primary Bjerknes force near the emitter becomes very large and tends to expel the bubbles up to a stagnation point. Two-dimensional axi-symmetric computations of the acoustic field created by a large area immersed sonotrode are also performed, and the paths of the bubbles in the resulting Bjerknes force field are sketched. Cone bubble structures are recovered and compare reasonably well to reported experimental results. The underlying mechanisms yielding such structures is examined, and it is found that the conical structure is generic and results from the appearance a sound velocity gradient along the transducer area. Finally, a more complex system, similar to an ultrasonic bath, in which the sound field results from the flexural vibrations of a thin plate, is also simulated. The calculated bubble paths reveal the appearance of other commonly observed structures in such configurations, such as streamers and flare structures.