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.     

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.     

Cavitation clouds created by shock scattering from bubbles during histotripsy

Histotripsy is a therapy that focuses short-duration, high-amplitude pulses of ultrasound to incite a localized cavitation cloud that mechanically breaks down tissue. To investigate the mechanism of cloud formation, high-speed photography was used to observe clouds generated during single histotripsy pulses. Pulses of 5-20 cycles duration were applied to a transparent tissue phantom by a 1-MHz spherically focused transducer. Clouds initiated from single cavitation bubbles that formed during the initial cycles of the pulse, and grew along the acoustic axis opposite the propagation direction. Based on these observations, we hypothesized that clouds form as a result of large negative pressure generated by the backscattering of shockwaves from a single bubble. The positive-pressure phase of the wave inverts upon scattering and superimposes on the incident negative-pressure phase to create this negative pressure and cavitation. The process repeats with each cycle of the incident wave, and the bubble cloud elongates toward the transducer. Finite-amplitude propagation distorts the incident wave such that the peak-positive pressure is much greater than the peak-negative pressure, which exaggerates the effect. The hypothesis was tested with two modified incident waves that maintained negative pressure but reduced the positive pressure amplitude. These waves suppressed cloud formation which supported the hypothesis.     

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.     

Bubble creation and collapse during excimer laser ablation of weak absorbing polymers

We present evidence suggesting that XeCl laser ablation of a weakly absorbing poly-methyl-methacrylate (PMMA) polymer, done by chemical, thermal bond breaking of the polymer chain or optical breakdown of the material, which involves plasma generation, creates a cloud of small asymmetric near the surface bubbles, which subsequently expand and aggregate during the same laser pulse duration or in subsequent pulses depending on the laser pulse energy. When a critical volume is reached each bubble collapses in a high pressure and temperature central point and rebounds ejecting a hot jet of material on the non-irradiated area of the polymer and creating craters on the surface. A characteristic bipolar pressure wave corresponding to the bubble collapse, explosion and rebound is observed. The number density of the craters on the surface is a function of the laser pulse sequence number and the laser pulse energy density.     

Ultrasound-induced lung hemorrhage: role of acoustic boundary conditions at the pleural surface

In a previous study [J. Acoust. Soc. Am. 108, 1290 (2000)] the acoustic impedance difference between intercostal tissue and lung was evaluated as a possible explanation for the enhanced lung damage with increased hydrostatic pressure, but the hydrostatic-pressure-dependent impedance difference alone could not explain the enhanced occurrence of hemorrhage. In that study, it was hypothesized that the animal's breathing pattern might be altered as a function of hydrostatic pressure, which in turn might affect the volume of air inspired and expired. The acoustic impedance difference between intercostal tissue and lung would be affected with altered lung inflation, thus altering the acoustic boundary conditions. In this study, 12 rats were exposed to 3 volumes of lung inflation (inflated: approximately tidal volume; half-deflated: half-tidal volume; deflated: lung volume at functional residual capacity), 6 rats at 8.6-MPa in situ peak rarefactional pressure (MI of 3.1) and 6 rats at 16-MPa in situ peak rarefactional pressure (MI of 5.8). Respiration was chemically inhibited and a ventilator was used to control lung volume and respiratory frequency. Superthreshold ultrasound exposures of the lungs were used (3.1-MHz, 1000-Hz PRF, 1.3-micros pulse duration, 10-s exposure duration) to produce lesions. Deflated lungs were more easily damaged than half-deflated lungs, and half-deflated lungs were more easily damaged than inflated lungs. In fact, there were no lesions observed in inflated lungs in any of the rats. The acoustic impedance difference between intercostal tissue and lung is much less for the deflated lung condition, suggesting that the extent of lung damage is related to the amount of acoustic energy that is propagated across the pleural surface boundary.     

Comparison of electrohydraulic lithotripters with rigid and pressure-release ellipsoidal reflectors. II. Cavitation fields.

Dramatically different cavitation was produced by two separate acoustic pulses that had different shapes but similar duration, frequency content, and peak positive and negative pressure. Both pulses were produced by a Dornier HM-3 style lithotripter: one pulse when the ellipsoidal reflector was rigid, the other when the reflector was pressure release. The cavitation, or bubble action, generated by the conventional rigid-reflector pulse was nearly 50 times longer lived and 3-13 times stronger than that produced by the pressure-release-reflector pulse. Cavitation durations measured by passive acoustic detection and high-speed video agreed with calculations based on the Gilmore equation. Cavitation intensity, or destructive potential, was judged (1) experimentally by the size of pits in aluminum foil detectors and (2) numerically by the calculated amplitude of the shock wave emitted by a collapsing bubble. The results indicate that the trailing positive spike in the pressure-release-reflector waveform stifles bubble growth and mitigates the collapse, whereas the trough after the positive spike in the rigid-reflector waveform triggers inertially driven growth and collapse. The two reflectors therefore provide a tool to compare effects in weakly and strongly cavitating fields and thereby help assess cavitation's role in lithotripsy.     

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.     

高重频超宽谱短电磁脉冲对GPS接收机干扰

超宽谱短电磁脉冲的频谱可覆盖GPS工作频带,对GPS接收机的正常工作存在干扰威胁。从理论分析、数值仿真和实验方面研究了高重频超宽谱短电磁脉冲对GPS接收机干扰效果与脉冲参数之间的依赖关系。结果表明:若脉冲重复频率整数倍能落入GPS接收机工作频带内,高重频超宽谱短电磁脉冲对GPS接收机干扰效果较强,且达到相同干扰效果时所需脉冲幅值随重频增大而等比例减小,即脉冲幅值与重频乘积保持为常数;若重频整数倍偏离GPS接收机工作频带,高重频超宽谱短电磁脉冲对GPS接收机干扰效果不明显。     

Sonoluminescence characterization of inertial cavitation inside a BSA phantom treated by pulsed HIFU

The aim of this study was to investigate the inertial cavitation inside a phantom treated by pulsed HIFU (pHIFU). Basic bovine serum albumin (BSA) phantoms without any inherent ultrasound contrast agents (UCAs) or phase-shift nano-emulsions (PSNEs) were used. During the treatment, sonoluminescence (SL) recordings were performed to characterize the spatial distribution of inertial cavitation adjacent to the focal region. High-speed photographs and thermal coagulations, comparing with the SL results, were also recorded and presented. A series of pulse parameters (pulse duration (PD) was between 1 and 23 cycles and pulse repetition frequency (PRF) was between 0.5 kHz and 100 kHz) were performed to make a systematic investigation under certain acoustic power (APW). Continuous HIFU (cHIFU) investigation was also performed to serve as control group. It was found that, when APW was 19.5 W, pHIFU with short PD was much easier to form SL adjacent to the focal region inside the phantom, while it was difficult for cHIFU to generate cavitation bubbles. With appropriate PD and PRF, the residual bubbles of the previous pulses could be stimulated by the incident pulses to oscillate in a higher level and even violently collapse, resulting to enhanced physical thermogenesis. The experimental results showed that the most violent inertial cavitation occurs when PD was set to 6 cycles (5 μs) and PRF to 10 kHz, while the highest level of thermal coagulation was observed when PD was set to 10 cycles. The cavitational and thermal characteristics were in good correspondence, exhibiting significant potentiality regarding to inject-free cavitation bubble enhanced thermal ablation under lower APW, compared to the conventional thermotherapy.     

Pulsed holmium laser ablation of tissue phantoms: correlation between bubble formation and acoustic transients

5 Pa served as tissue phantoms to evaluate such effects. Holmium laser pulses (wavelength: 2.12 μm, duration: 180 μs FWHM), were delivered through 400 and 600 μm diameter optical fibers inserted into cubes of clear gel. Bubble effects were investigated using simultaneous flash micro-videography and pressure recording for radiant exposures of 20–382 J/cm². Bubble formation and bubble collapse induced pressure transients were observed regardless of phantom stiffness. Bubbles of up to 4.2 mm in length were observed in gels with a Young’s modulus of 2.9×10⁵ Pa at a pulse energy of 650 mJ. An increase of Young’s modulus (reduction in water content) led to a monotonic reduction of bubble size. In the softest gels, bubble dimensions exceeded those observed in water. Pressure amplitudes at 3 mm decreased from 100±14 bars to 17±6 bars with increasing Young’s modulus over the studied range. Theoretical analysis suggested a major influence on bubble dynamics of the mass and energy transfer through the bubble boundary. Received: 26 August 1996/Revised version: 10 February 1997     

激光空泡溃灭及其产生的声波

强激光脉冲在水中的自聚焦传输、成丝、击穿及击穿后产生的声波,近年来成为强激光脉冲传输应用研究领域的一个热点。强激光脉冲电离产生的空泡在溃灭过程中,对周围水体产生压缩,从而在水下产生声波。在现有理论基础上,考虑空泡含气量、水的粘滞系数和水的表面张力系数对空泡运动及其产生声波的影响。给出双空泡运动方程,分析空泡间距对空泡溃灭和其产生声压关系。根据实际情况,计算不同温度情况下单空泡和双空泡运动过程及其产生的声压,并进行相互比较。计算结果表明: 水温越高,空泡运动时达到的最小半径越小,空泡振荡周期和溃灭时间延长,产生声压越高。随双空泡间距减小,空泡溃灭时达到的最小半径线性减小,而其产生的最大声压则单调增大。     

The pulsed microwave damage trend of a bipolar transistor as a function of pulse parameters

In the present paper we conduct a theoretical study of the thermal accumulation effect of a typical bipolar transistor caused by high power pulsed microwaves(HPMs),and investigate the thermal accumulation effect as a function of pulse repetition frequency(PRF) and duty cycle.A study of the damage mechanism of the device is carried out from the variation analysis of the distribution of the electric field and the current density.The result shows that the accumulation temperature increases with PRF increasing and the threshold for the transistor is about 2 kHz.The response of the peak temperature induced by the injected single pulses indicates that the falling time is much longer than the rising time.Adopting the fitting method,the relationship between the peak temperature and the time during the rising edge and that between the peak temperature and the time during the falling edge are obtained.Moreover,the accumulation temperature decreases with duty cycle increasing for a certain mean power.     

A theoretical study of cavitation generated by an extracorporeal shock wave lithotripter

The intense acoustic wave generated at the focus of an extracorporeal shock wave lithotripter is modeled as the impulse response of a parallel RLC circuit. The shock wave consists of a zero rise time positive spike that falls to 0 at 1 microsecond followed by a negative pressure component 6 microseconds long with amplitudes scaled to +1000 and -160 bars, P+ and P-, respectively. This pressure wave drives the Gilmore-Akulichev formulation for bubble dynamics; the zero-order effect of gas diffusion on bubble response is included. The negative pressure component of a 1000-bar shock wave will cause a preexisting bubble in the 1- to 10-microns range to expand to over 100 times its initial size, R0, for 250 microseconds, with a peak radius of approximately 1400 microns, then collapse very violently, emitting far UV or soft x-ray photons (black body). Gas diffusion does not appreciably mitigate the amplitude of the pressure wave radiated at the primary collapse, but does significantly reduce the collapse temperature. Diffusion also increases the bubble radius from R0 up to 40 microns and extends the duration of ringing following the primary collapse, assuming that the bubble does not break up or shed microbubbles. Results are sensitive to P+/P- and to the duration of the negative pressure cycle but not to rise time.     

High Speed Visualization and Dynamic Measurement of Heat Driven Pumps

We provide the high speed flow visualization and dynamic measurement results for the U-shaped and the inverted U-shaped heat driven pumps. The U-shaped heat driven pumps at the high heating powers consist of a succession of tiny bubble nucleation, growth and coalescence process. Once the “larger” spherical bubble or the bubble slug forms, it expands quickly in both upstream and downstream directions. The increased pressure leads to the liquid discharge through the outlet check valve. When the advancing vapor/liquid interface reaches a higher position in the vertical discharge branch, the condensation heat transfer in the discharge branch shrinks the bubble slug, leading to the decreased pressure and initiating the open of the inlet check valve. Thus the fresh liquid can be sucked into the system. Heat driven pumps operating at the low heating powers display the similar process. However, two major differences are identified: (1) A full cycle includes a set of positive pressure pulses corresponding to a set of tiny bubble nucleation, growth and coalescence process in each substage. Only at the end of the cycle, an apparent negative pressure pulse is created. (2) For each substage in each cycle, when the newly formed bubble slug is chasing the ahead “old” bubble slug, the deformed liquid bridge is formed due to the gravity force effect. When the two bubble slugs are merging together, a wave vapor/liquid interface occurs along the bottom of the capillary tube. For the inverted U-shaped heat driven pumps, there are fewer positive pressure pulses included, corresponding to lesser number of new bubble nucleation, growth, and coalescence process. The bubble slug in the capillary tube is very standard with the smooth vapor/liquid interface. The cycle periods and the pumping flow rates are given versus the heating powers.     

含气量对液体中空泡声波频谱特性的影响

通过压电陶瓷（PZT）水听器获取了液体中激光空泡脉动辐射的声波,并计算了激光空泡在第1次脉动过程中泡内的含气量,结合空泡含气量对空泡最大半径及脉动周期影响的分析,进而分析了含气量对空泡声波频谱特性的影响。分析结果表明:激光空泡第1次脉动过程中泡内的含气量随着作用激光能量的增加而增加,含气量的多少将直接影响空泡运动的剧烈程度;含气量越多,空泡脉动越缓慢,脉动周期越长,空泡脉动辐射声波的峰值频率有向低频移动的趋势。     

Pulsed microwave damage trend of bipolar transistor as a function of pulse parameters

In the present paper we conduct a theoretical study of the thermal accumulation effect of a typical bipolar transistor caused by high power pulsed microwave (HPM), and investigate the thermal accumulation effect as a function of pulse repetition frequency (PRF) and duty cycle. A study of the damage mechanism of the device is carried out from the variation analysis of the distribution of the electric field and the current density. The result shows that the accumulation temperature increases with PRF increasing and the threshold for the transistor is about 2 kHz. The response of the peak temperature induced by the injected single pulses indicates that the falling time is much longer than the rising time. Adopting the fitting method, the relationship between the peak temperature and the time during the rising edge and that between the peak temperature and the time during the falling edge are obtained. Moreover, the accumulation temperature decreases with duty cycle increasing for a certain mean power.     

Shock wave interaction with laser-generated single bubbles

The interaction of a lithotripter shock wave (LSW) with laser-generated single vapor bubbles in water is investigated using high-speed photography and pressure measurement via a fiber-optic probe hydrophone. The interaction leads to nonspherical collapse of the bubble with secondary shock wave emission and microjet formation along the LSW propagation direction. The maximum pressure amplification is produced during the collapse phase of the bubble oscillation when the compressive pulse duration of the LSW matches with the forced collapse time of the bubble.     

Effect of surface tension on a liquid-jet produced by the collapse of a laser-induced bubble against a rigid boundary

The effect of surface tension on the behavior of a liquid-jet is investigated experimentally by means of a fiber-coupled optical beam deflection (OBD) technique. It is found that a target under water is impacted in turn by a laser-plasma ablation force and by a high-speed liquid-jet impulse induced by bubble collapse in the vicinity of a rigid boundary. The liquid-jet impact is found to be the main damage mechanism in cavitation erosion. Furthermore, the liquid-jet increases monotonously with surface tension, so cavitation erosion rises sharply with increasing surface tension. Surface tension also reduces bubble collapse duration. From the experimental results and the modified Rayleigh theory, the maximum bubble radius is obtained and it is found to reduce with increasing surface tension.     

脉冲超声激励下SonoVue微泡的瞬态空化特性

将SonoVue微泡从临床疾病诊断拓展至治疗引起了诸多研究人员的兴趣。为了平衡治疗效率和生物安全性,深入理解声学参数和SonoVue微泡瞬态空化的关系至关重要。本研究自行制备仿体容器放置SonoVue微泡,使用1 MHz发射换能器激励其产生空化效应,另一个7.5 MHz的聚焦换能器接收声信号,经放大及高速数据采集后送上位机处理。通过深入分析信号的时频域特征,我们提出以宽带信号的能量及其随时间变化曲线的半高宽来表征瞬态空化的剂量(ICD)和相对持续时间(ICP),并确定:瞬态空化的发生和ICD依赖于峰值负声压,但ICP随峰值负声压的增加而减小;脉冲重复频率和脉冲持续时间都和ICD及ICP正相关;且脉冲持续时间的影响较大。这些结果有望为SonoVue微泡的治疗应用提供理论支持。