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Passive cavitation mapping, which generates images using bubble acoustic emission signals, has been increasingly used for monitoring and guiding focused ultrasound surgery. Passive cavitation mapping can be used as an adjunct to magnetic resonance imaging to provide crucial information on the safety and efficacy of focused ultrasound surgery. The most widely used algorithm for passive cavitation mapping is delay-and-sum. One of the major limitations of delay-and-sum is its suboptimal computational efficiency. Although frequency-domain delay-and-sum can partially resolve this issue, such an algorithm is not suitable for imaging the evolution of bubble activity in real time and for cases in which cavitation events occur asynchronously. This study investigates a transient angular spectrum approach for passive cavitation mapping. The working principle of this approach is to back propagate the received signal to the domain of interest and reconstruct the spatial-temporal wave field encoded with the bubble location and collapse time. The transient angular spectrum approach is validated using an in silico model and water bath experiments. It is found that the transient angular spectrum approach yields similar results to delay-and-sum, but it is one order of magnitude faster. The results obtained by this study suggest that the transient angular spectrum approach is promising for fast and accurate passive cavitation mapping.

OBJECTIVE: To investigate the mechanism of stone dusting in Holmium (Ho): YAG laser lithotripsy (LL). MATERIALS AND METHODS: Cylindrical BegoStone samples (6 × 6 mm, H × D) were treated in water using a clinical Ho:YAG laser lithotripter in dusting mode (0.2–0.4 J with 70–78 μs in pulse duration, 20 Hz) at various fiber tip to stone standoff distances (SD = 0, 0.5, and 1 mm). Stone damage craters were quantified by optical coherence tomography and bubble dynamics were captured by high-speed video imaging. To differentiate the contribution of cavitation vs thermal ablation to stone damage, three additional experiments were performed. First, presoaked wet stones were treated in air to assess stone damage without cavitation. Second, the laser fiber was advanced at various offset distances (OSD = 0.25, 1, 2, 3, and 10 mm) from the tip of a flexible ureteroscope to alter the dynamics of bubble collapse. Third, stones were treated with parallel fiber to minimize photothermal damage while isolating the contribution of cavitation to stone damage. RESULTS: Treatment in water resulted in 2.5- to 90-fold increase in stone damage compared with those produced in air where thermal ablation dominates. With the fiber tip placed at OSD = 0.25 mm, the collapse of the bubble was distracted away from the stone surface by the ureteroscope tip, leading to significantly reduced stone damage compared with treatment without the scope or with scope at large OSD of 3–10 mm. The average crater volume produced by parallel fiber orientation at 0.2 J after 100 pulses, where cavitation is the dominant mechanism of stone damage, was comparable with those produced by using perpendicular fiber orientation within SD = 0.25–1 mm. CONCLUSION: Cavitation plays a dominant role over photothermal ablation in stone dusting during short pulse Ho:YAG LL when 10 or more pulses are delivered to the same location.

Shock wave lithotripsy (SWL) has been widely used for non-invasive treatment of kidney stones. Cavitation plays an important role in stone fragmentation, yet it may also contribute to renal injury during SWL. It is therefore crucial to determine the spatiotemporal distributions of cavitation activities to maximize stone fragmentation while minimizing tissue injury. Traditional cavitation detection methods include high-speed optical imaging, active cavitation mapping (ACM), and passive cavitation mapping (PCM). While each of the three methods provides unique information about the dynamics of the bubbles, PCM has most practical applications in biological tissues. To image the dynamics of cavitation bubble collapse, we previously developed a sliding-window PCM (SW-PCM) method to identify each bubble collapse with high temporal and spatial resolution. In this work, to further validate and optimize the SW-PCM method, we have developed tri-modality cavitation imaging that includes three-dimensional high-speed optical imaging, ACM, and PCM seamlessly integrated in a single system. Using the tri-modality system, we imaged and analyzed laser-induced single cavitation bubbles in both free field and constricted space and shock wave-induced cavitation clusters. Collectively, our results have demonstrated the high reliability and spatial-temporal accuracy of the SW-PCM approach, which paves the way for the future in vivo applications on large animals and humans in SWL.

In this manuscript, we first describe the fabrication protocol of a microfluidic chip, with gold dots and fibronectin-coated regions on the same glass substrate, that precisely controls the generation of tandem bubbles and individual cells patterned nearby with well-defined locations and shapes. We then demonstrate the generation of tandem bubbles by using two pulsed lasers illuminating a pair of gold dots with a few-microsecond time delay. We visualize the bubble-bubble interaction and jet formation by high-speed imaging and characterize the resultant flow field using particle image velocimetry (PIV). Finally, we present some applications of this technique for single cell analysis, including cell membrane poration with macromolecule uptake, localized membrane deformation determined by the displacements of attached integrin-binding beads, and intracellular calcium response from ratiometric imaging. Our results show that a fast and directional jetting flow is produced by the tandem bubble interaction, which can impose a highly localized shear stress on the surface of a cell grown in close proximity. Furthermore, different bioeffects can be induced by altering the strength of the jetting flow by adjusting the standoff distance from the cell to the tandem bubbles.

In shock wave lithotripsy (SWL), acoustic pulses with a leading compression wave followed by a tensile wave are delivered into the patient’s body using a water-filled coupling cushion. Cavitation-related acoustic energy loss in the coupling unit depends critically on water conditions, e.g. dissolved gas concentration and exchange flow rate. We have systematically investigated the attenuation mechanism in the coupling water via pressure measurements and cavitation characterization. In non-degassed water the bubble cluster became progressively dense (i.e., proliferated because of gas diffusion into bubbles and splitting of bubbles into many daughter bubbles) in shock waves delivered at 1 Hz leading to reduction in the tensile wave duration from a nominal value of 4.6 to 1.8 µs. To reduce cavitation in the coupling water along the beam path, we have used a continuous jet flow to remove residual daughter bubbles between consecutive shocks. As a result, stone fragmentation efficiency was increased from 16±4% t...

Carefully timed tandem microbubbles have been shown to produce directional and targeted membrane poration of individual cells in microfluidic systems, which could be of use in ultrasound-mediated drug and gene delivery. This study aims at contributing to the understanding of the mechanisms at play in such an interaction. The dynamics of single and tandem microbubbles between two parallel plates is studied numerically and analytically. Comparisons are then made between the numerical results and the available experimental results. Numerically, assuming a potential flow, a three-dimensional boundary element method (BEM) is used to describe complex bubble deformations, jet formation, and bubble splitting. Analytically, compressibility and viscous boundary layer effects along the channel walls, neglected in the BEM model, are considered while shape of the bubble is not considered. Comparisons show that energy losses modify the bubble dynamics when the two approaches use identical initial conditions. The initial conditions in the boundary element method can be adjusted to recover the bubble period and maximum bubble volume when in an infinite medium. Using the same conditions enables the method to recover the full dynamics of single and tandem bubbles, including large deformations and fast re-entering jet formation. This method can be used as a design tool for future tandem-bubble sonoporation experiments.

Previous studies have demonstrated that stone comminution decreases with increased pulse repetition frequency as a result of bubble proliferation in the cavitation field of a shock wave lithotripter (Pishchalnikov et al 2011 J. Acoust. Soc. Am. 130 EL87-93). If cavitation nuclei remain in the propagation path of successive lithotripter pulses, especially in the acoustic coupling cushion of the shock wave source, they will consume part of the incident wave energy, leading to reduced tensile pressure in the focal region and thus lower stone comminution efficiency. We introduce a method to remove cavitation nuclei from the coupling cushion between successive shock exposures using a jet of degassed water. As a result, pre-focal bubble nuclei lifetime quantified by B-mode ultrasound imaging was reduced from 7 to 0.3 s by a jet with an exit velocity of 62 cm s(-1). Stone fragmentation (percent mass2 mm) after 250 shocks delivered at 1 Hz was enhanced from 22 ± 6% to 33 ± 5% (p = 0.007) in water without interposing tissue mimicking materials. Stone fragmentation after 500 shocks delivered at 2 Hz was increased from 18 ± 6% to 28 ± 8% (p = 0.04) with an interposing tissue phantom of 8 cm thick. These results demonstrate the critical influence of cavitation bubbles in the coupling cushion on stone comminution and suggest a potential strategy to improve the efficacy of contemporary shock wave lithotripters.

Kidney stones are a common and painful affliction, but fortunately physics offers some relief: Sound can be used to break up the stones, without invasive surgery. Efficacy of this ``lithotripsy'' treatment, however, depends strongly on cavitation, which can both attenuate the sound waves and provoke significant tissue damage. In this collaboration between a physicist, engineers, and materials scientists, our understanding of this process is advanced through measurements and modeling, providing insight into the relations between bubble dynamics and lithotripsy effectiveness.

The mechanism responsible for the development of autocyclic circular breakdowns in electrolyte as a result of the electric discharge within a hole in a dielectric plate has been experimentally studied. It is demonstrated that the breakdowns are caused by an axisymmetric electrohydrodynamic process involving the formation of a circular bubble breakdown, which acts as a current interrupter in the stage of expansion and as a switch in the stage of collapse, which is followed by the circular breakdown. On the whole, a self-adjusting antiphase process of bubble generation dynamics is developed in the system, whereby each preceding bubble collapses, in the field of pressure due to the subsequent bubble breakdown. This collapse proceeds at an accelerated rate and is accompanied by the fractionation of bubbles.

The early stage of the dynamics of interacting cavitation bubbles in a transmitted spherically focused pulsed wave consisting of compression and rarefaction phases is studied. The cavitation is investigated away from the liquid boundaries for negative pressures up to −42 MPa with a decrease rate of −40 MPa/μs by high-speed microscopic filming (100 million frames per second and a spatial resolution of 5–50μm/pixel) and pressure measurements. It is demonstrated that, according to the kinematics of size variation, the bubbles are separated into two fractions: expanding and collapsing ones. Experimental data provide grounds to assume that the formation of a two-fraction bubble cluster occurs on account of different threshold values of pressure in the rarefaction wave for two characteristic sizes of nuclei, namely, micronuclei (d I < 10μm) and nanonuclei (“bubstons,” d II ∼ 1 nm), which become detectable only when the rarefaction wave amplitude exceeds the critical one. Pulsed compression of small bubbles in the process of transformation of a rarefaction wave into a compression wave occurs under the effect of a cluster’s internal pressure up to 20 MPa and proceeds with the conservation of the spherical shape of the second-fraction bubbles. It is demonstrated that the velocity of the center of mass of a bubble reaches its peak value close to the moment of bubble collapse. The translational and radial dynamics of a bubble are studied in a numerical experiment using the Rayleigh-Plesset equation and taking into account the viscous force and the pressure gradient. The results of measuring the translational shift may be useful for estimating the minimum bubble radius by comparing the numerical results with the experiment.

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.

The dynamic interaction between laser-generated tandem bubble and individual polystyrene particles of 2 and 10 μm in diameter is studied in a microfluidic channel (25 μm height) by high-speed imaging and particle image velocimetry. The asymmetric collapse of the tandem bubble produces a pair of microjets and associated long-lasting vortices that can propel a single particle to a maximum velocity of 1.4 m/s in 30 μs after the bubble collapse with a resultant directional displacement up to 60 μm in 150 μs. This method may be useful for high-throughput cell sorting in microfluidic devices.

The dynamic interaction of a shockwave (modelled as a pressure pulse) with an initially spherically oscillating bubble is investigated. Upon the shockwave impact, the bubble deforms non-spherically and the flow field surrounding the bubble is determined with potential flow theory using the boundary-element method (BEM). The primary advantage of this method is its computational efficiency. The simulation process is repeated until the two opposite sides of the bubble surface collide with each other (i.e. the formation of a jet along the shockwave propagation direction). The collapse time of the bubble, its shape and the velocity of the jet are calculated. Moreover, the impact pressure is estimated based on water-hammer pressure theory. The Kelvin impulse, kinetic energy and bubble displacement (all at the moment of jet impact) are also determined. Overall, the simulated results compare favourably with experimental observations of lithotripter shockwave interaction with single bubbles (using laser-induced bubbles at various oscillation stages). The simulations confirm the experimental observation that the most intense collapse, with the highest jet velocity and impact pressure, occurs for bubbles with intermediate size during the contraction phase when the collapse time of the bubble is approximately equal to the compressive pulse duration of the shock wave. Under this condition, the maximum amount of energy of the incident shockwave is transferred to the collapsing bubble. Further, the effect of the bubble contents (ideal gas with different initial pressures) and the initial conditions of the bubble (initially oscillating vs. non-oscillating) on the dynamics of the shockwave-bubble interaction are discussed.

Understanding the dynamics of bubble oscillation in tissue-constrained media such as within blood vessels is important for many current and potential therapeutic ultrasound applications. Cavitation is a primary mechanism responsible for vessel rupture and tissue injury in shock wave lithotripsy [1]. In sonoporation cavitation can be used to increase permeability of biological membranes. Particularly, ultrasound contrast agents are widely used for imaging of blood vessels and for enhancement of ultrasound-mediated gene delivery [2]. Modeling of non-linear oscillations of bubbles in acrylic capillaries in a high-intensity focused ultrasound field revealed a clear dependence of bubble displacement and fragmentation on tube diameter [3]. However, the effect of elastic boundary on bubble dynamics may differ significantly from that of a rigid boundary [4, 5]. In this study, experimental investigation of the dynamics of bubble oscillation in an elastic tube was performed and preliminary results from tubes of different inner diameters are presented.Copyright © 2007 by ASME

The interaction of laser-generated single inertial bubbles (collapse $\text{time}=121\phantom{\rule{0.3em}{0ex}}\ensuremath{\mu}\mathrm{s}$) near a silicon rubber membrane with a shock wave ($55\phantom{\rule{0.3em}{0ex}}\mathrm{MPa}$ in peak pressure and $1.7\phantom{\rule{0.3em}{0ex}}\ensuremath{\mu}\mathrm{s}$ in compressive pulse duration) is investigated. The interaction leads to directional, forced asymmetric collapse of the bubble with microjet formation toward the surface. Maximum jet penetration into the membrane is produced during the bubble collapse phase with optimal shock wave arrival time and stand-off distance. Such interaction may provide a unique acoustic means for in vivo microinjection, applicable to targeted delivery of macromolecules and gene vectors to biological tissues.

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.

Cavitation damage is responsible for initial pitting of kidney stone surfaces, damage that is thought to play an important role in shock wave lithotripsy. We introduce a multiscale model of the formation of cavitation bubbles in water, and subsequent breakdown. At a macroscopic, continuum scale cavitation is modeled by the 3D Euler equations with a Tait equation of state. Adaptive mesh refinement is used to provide increased resolution at the liquid/vapor boundary. Cells with both liquid and vapor phases are flagged by the continuum solver for mesoscale, kinetic modeling by a lattice Boltzmann description capable of capturing non-equilibrium behavior (e.g., phase change, energetic jet impingement). Isolated and interacting two-bubble configurations are studied. Computational simulation results are compared with high-speed experimental imaging of individual bubble dynamics and bubble–bubble interaction. The model is used to build a statistical description of multiple-bubble interaction, with input from cavitation cloud imaging. [Work supported by NIH through 5R37DK052985-18.]

Recent experiments, motivated by ultrasound-mediated drug and gene delivery, have utilized laser-generated tandem microbubbles to produce directional and targeted membrane poration of individual cells in microfluidic systems [Sankin et al., Phys. Rev. Lett. 105, 078101 (2010)]. Two models describing the dynamics of coupled bubbles between parallel plates have been applied to understand these observations. The first approach is based on the Boundary Element Method in both 2D and 3D coordinate systems for bubbles bounded by finite rigid plates. Deformation of the bubble surfaces is taken into account, capturing phenomena such as bubble jetting and fragmentation [Hsiao et al., Ultrasound Med. Biol. 36, 2065-2079 (2010)]. The second approach is semi-analytic, accounts for fluid compressibility and elasticity of the plates, but is limited to spherical bubble pulsation [Hay et al., J. Acoust. Soc. Am. 129, 2477(A) (2011)]. Observations of tandem bubble interaction with adjacent biological cells and their potent...

The dynamics of tandem bubble interaction in a microfluidic channel (800 × 21 μm, W × H) have been investigated using high-speed photography, with resultant fluid motion characterized by particle imaging velocimetry. A single or tandem bubble is produced reliably via laser absorption by micron-sized gold dots (6 μm in diameter with 40 μm in separation distance) coated on a glass surface of the microfluidic channel. Using two pulsed Nd:YAG lasers at λ = 1064 nm and ∼10 μJ/pulse, the dynamics of tandem bubble interaction (individual maximum bubble diameter of 50 μm with a corresponding collapse time of 5.7 μs) are examined at different phase delays. In close proximity (i.e., interbubble distance = 40 μm or γ = 0.8), the tandem bubbles interact strongly with each other, leading to asymmetric deformation of the bubble walls and jet formation, as well as the production of two pairs of vortices in the surrounding fluid rotating in opposite directions. The direction and speed of the jet (up to 95 m/s), as well as the orientation and strength of the vortices can be varied by adjusting the phase delay.

Understanding the dynamic interaction of cavitation bubbles with biological tissue is central to the effective and safe application of therapeutic ultrasound in clinical medicine. Coupled oscillation of two laser generated microbubbles (maximum radius = 28 μm) in constrained media and associated shear stresses are investigated experimentally. Bubble‐bubble interaction in a microchannel of 25‐μm height is observed using high‐speed video cameras and μPIV technique. Two liquid micro‐jets moving in opposite directions can be generated when the second bubble is produced at the maximum size of the first one. The interaction of these tandem microbubbles with single cell leads to controllable poration of adjacent cell membrane and dye uptake. Micro‐PIV data are compared with cell viability at various bubble‐cell distances and azimuthal orientations. This method provides a new approach for highly selective cell treatment in situ applicable to targeted microinjection of macromolecules and gene vectors in microfluid...

Coupled oscillations of two adjacent laser‐induced microbubbles have been shown to produce unique asymmetric bubble deformation and microjet formation. The resultant microstreaming and shear stress can cause localized cell membrane poration with potential application in targeted drug and gene delivery. In this study, we investigate the bubble dynamics and flow field produced by laser‐generated tandem microbubble in a microfluidic device. Flow field around the tandem microbubble is analyzed with respect to phase delay, inter‐bubble distance, and size ratio between the two microbubbles. In addition, micropatterning technique is used to control the adhesion site and growth pattern of HeLa cells in relation to the tandem microbubble. Flow vorticity is observed to be a key parameter that correlates with the strength of tandem microbubble oscillation and resultant macromolecule uptake efficiency. [Work supported by NIH Grant Nos. R01DK052985, R21CA135221, and S10RR016802].

Coupled oscillation of two laser generated microbubbles (maximum radius = 28 μm) and associated shear stresses are investigated experimentally. Bubble‐bubble interaction in a microchannel of 25 μm height is observed using high‐speed video cameras and μPIV technique. Two liquid microjets moving in opposite directions can be generated when the second bubble is produced at the maximum size of the first one. The interaction of these tandem microbubbles with single cell leads to controllable poration of adjacent cell membrane and dye uptake. μPIV data are compared with cell viability at various bubble‐cell distances and azimuthal orientations. This method provides a new approach for highly selective cell treatment in situ, applicable to targeted microinjection of macromolecules and gene vectors in microfluidics devices. [Work supported in part by NIH.]

Recent studies have highlighted the potential for using laser‐induced micro‐cavitation in lab‐on‐a‐chip devices. Shear stress in a liquid can be controlled and significantly enhanced by bubble‐bubble interaction, providing new options for in situ cell treatment. Two micro‐bubbles (10 μs life time) are generated in a 25‐μm liquid layer using 5 ns tandem laser pulses delivered through the objective of a microscope. Bubble‐bubble interaction in nearly two‐dimensional flow is observed using high‐speed video cameras. Two liquid micro‐jets moving in opposite directions can be generated when the second bubble is produced at the maximum size of the first one. The jet velocity is estimated about 35 m/s. Particle imaging velocimetry reveals vortex flow motion around the oscillating bubble lasting for about 200 μs. Cell lyses produced by jetting from asymmetric oscillation of tandem microbubbles are investigated at various bubble‐cell distances and compared with the results from single symmetric bubble oscillation. ...

A method to characterize shock wave lithotripters by examining the potential for cavitation associated with the lithotripter shock wave (LSW) has been developed. The method uses the maximum radius achieved by a bubble subjected to a LSW as a representation of the cavitation potential for that region in the lithotripter. It is found that the maximum radius is determined by the work done on a bubble by the LSW. The method is used to characterize two reflectors: an ellipsoidal reflector and an ellipsoidal reflector with an insert. The results show that the use of an insert reduced the -6 dB volume (with respect to peak positive pressure) from 1.6 to 0.4 cm(3), the -6 dB volume (with respect to peak negative pressure) from 14.5 to 8.3 cm(3), and reduced the volume characterized by high cavitation potential (i.e., regions characterized by bubbles with radii larger than 429 µm) from 103 to 26 cm(3). Thus, the insert is an effective way to localize the potentially damaging effects of shock wave lithotripsy, and suggests an approach to optimize the shape of the reflector.

The interaction of laser‐generated single cavitation bubbles (maximum diameter Dmax=1.34 mm) near a silicon rubber membrane with a shock wave (39–75 MPa in peak pressure and 1.7 μs in compressive pulse duration) is investigated. The interaction leads to directional, forced collapse of the bubble with microjet formation along shock wave propagation direction. Maximum jet penetration into the membrane is produced during the bubble collapse phase with optimal shock wave arrival time and stand‐off distance s, a condition that ensures that the forced collapse time of the bubble matches with the compressive duration of the shock wave to generate presumably the maximum axial jet velocity toward the boundary. A maximum penetration depth of 0.5 mm is observed at dimensionless proximity γ (=2s/Dmax)=0.7 when the bubble establishes contact with the boundary during expansion. At larger γ (≥1.2), jet impact is significantly attenuated by the interposing water layer separating the collapsing bubble and the membrane sur...

The change in the current in an electrochemical cell is studied simultaneously with the dynamics and luminescence of a solitary cavitation bubble produced by focusing a shock wave near a disk anode 0.6 mm in diameter in an NaCl solution. The current is maximum at the instant of the bubble collapse. The increase in the current is due to the mass transfer near the electrode intensified by the hydrodynamic flow around the bubble.