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During clinical procedures, the lithotripter shock wave (LSW) that is incident on the stone and resultant stress field is often asymmetric due to the respiratory motion of the patient. The variations of the LSW-stone interaction and associated fracture pattern were investigated by photoelastic imaging, phantom experiments, and three-dimensional fluid-solid interaction modeling at different lateral locations in a lithotripter field. In contrast to a T-shaped fracture pattern often observed in the posterior region of the disk-shaped stone under symmetric loading, the fracture pattern gradually transitioned to a tilted L-shape under asymmetric loading conditions. Moreover, the model simulations revealed the generation of surface acoustic waves (SAWs), i.e., a leaky Rayleigh wave on the anterior boundary and Scholte wave on the posterior boundary of the stone. The propagation of SAWs on the stone boundary is accompanied by a progressive transition of the LSW reflection pattern from regular to von Neumann and to weak von Neumann reflection near the glancing incidence and, concomitantly, the development and growth of a Mach stem, swirling around the stone boundary. The maximum tensile stress and stress integral were produced by SAWs on the stone boundary under asymmetric loading conditions, which drove the initiation and extension of surface cracks into the bulk of the stone that is confirmed by micro-computed tomography analysis.

A multiphysics computational model of the focusing of an acoustic pulse and subsequent shock wave formation that occurs during extracorporeal shock wave lithotripsy is presented. In the electromagnetic lithotripter modeled in this work the focusing is achieved via a polystyrene acoustic lens. The transition of the acoustic pulse through the solid lens is modeled by the linear elasticity equations and the subsequent shock wave formation in water is modeled by the Euler equations with a Tait equation of state. Both sets of equations are solved simultaneously in subsets of a single computational domain within the BEARCLAW framework which uses a finite-volume Riemann solver approach. This model is first validated against experimental measurements with a standard (or original) lens design. The model is then used to successfully predict the effects of a lens modification in the form of an annular ring cut. A second model which includes a kidney stone simulant in the domain is also presented. Within the stone the linear elasticity equations incorporate a simple damage model.

Using a reflector insert, the original HM-3 lithotripter field at 20 kV was altered significantly with the peak positive pressure (p(+)) in the focal plane increased from 49 to 87 MPa while the -6 dB focal width decreased concomitantly from 11 to 4 mm. Using the original reflector, p(+) of 33 MPa with a -6 dB focal width of 18 mm were measured in a pre-focal plane 15-mm proximal to the lithotripter focus. However, the acoustic pulse energy delivered to a 28-mm diameter area around the lithotripter axis was comparable ( approximately 120 mJ). For all three exposure conditions, similar stone comminution ( approximately 70%) was produced in a mesh holder of 15 mm after 250 shocks. In contrast, stone comminution produced by the modified reflector either in a 15-mm finger cot (45%) or in a 30-mm membrane holder (14%) was significantly reduced from the corresponding values (56% and 26%) produced by the original reflector (no statistically significant differences were observed between the focal and pre-focal planes). These observations suggest that a low-pressure/broad focal width lithotripter field will produce better stone comminution than its counterpart with high-pressure/narrow focal width under clinically relevant in vitro comminution conditions.

A previously introduced model for stone comminution in shock wave lithotripsy is extended to include damage produced by cavitation. At the macroscopic, continuum level a 3D elasticity model with time-varying material constants capturing localized damage provides the overall stress field within kidney stone simulants. Regions of high stress are identified and a mesoscopic crack propagation is used to dynamically update localized damage. The crack propagation model in turn is linked with a microscopic grain dynamics model. Continuum stresses and surface pitting is provided by a multiscale cavitation model (see related talk). The overall procedure is capable of tracking stone fragments and surface cavitation of the fragments through several levels of breakdown. Computed stone fragment distributions are compared to experimental results. [Work supported by NIH through 5R37DK052985-18.]

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.]

A challenge in clinical shock wave lithotripsy (SWL) is stone translation due to a patient’s respiratory motion, in a direction perpendicular to shockwave propagation, which may negatively affect stone comminution while increasing the risk of tissue injury. We have developed a method using external masks and a modified lens geometry to transform the axisymmetric pressure distribution in the focal plane of an electromagnetic lithotripter into a non-axisymmetric elliptical distribution. At equivalent acoustic pulse energy (46 mJ), the peak pressure was reduced from 44 MPa to 38 MPa while the −6 dB focal width was increased from 7.4 mm for the original to 11.7 mm (major axis) and 7.9 mm (minor axis) of the modified field. In vitro stone comminution was performed in a tube holder (d = 14 mm) using a translation pattern with 12 breaths per minute and 15 mm in excursion distance. Stone comminution after 1000 shocks are 71.2 ± 4.4% and 65.2 ±8.3% (p

Cavitation induced bioeffects has not been resolved satisfactorily due to the randomness in the inception and bubble dynamics produced by ultrasound. We have developed a microfluidic system to observe consistently the interaction of laser-generated tandem bubbles (50 μm in diameter) with resultant jet formation, cell deformation, and localized membrane rupture with progressive diffusion of propodium iodide (PI) into individual HeLa cells placed nearby. We observe a clear stand-off distance (SD) dependence in the bioeffects produced by the tandem bubbles. At SD of 10 μm, all cells underwent necrosis with high, unsaturated level of PI uptake. At SD of 20~30 μm, 58 to 80% of the cells showed repairable membrane poration with low to medium but saturated level of PI uptake. Within this range, the sub-population of cells that survived without apoptosis increased from ~9% at SD of 20 μm to ~70% at SD of 30 μm. The maximum PI uptake, pore size, and estimated membrane strain, however, could vary by more than an order of magnitude at each SD. At SD of 40 μm, no detectable PI uptake was observed. This experimental system provides a unique tool to probe the bioeffects of cavitation at the single cell level.

Previous research shows that a shockwave’s tensile phase can be strongly attenuated as a function of gas concentration in the coupling medium. Here, we seek to elucidate the relationship between tensile attenuation and gas concentration via pressure measurements at the focus and highspeed imaging. By performing in vitro experiments with water of varying gas concentrations (2.05 mg/L, 4.30 mg/L, and 6.50 mg/L), the negative impulsive pressure is correlated to the density of the bubble cloud that occurs in the beampath. It is found that for gas contents below 4 mg/L the bubble cloud remains sparse and the shockwave’s tensile phase is successfully transmitted with no loss in impulsive pressure. For gas contents 4 mg/L and above the bubble cloud becomes highly dense and prevents transmission with up to a 75% loss in impulsive pressure. Corresponding stone comminution experiments show that the treatment efficiency sharply decreases with increasing gas concentration. These results underlie the importance of degassing the water used in the coupling medium before treatment.

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...

To assess the role of stress waves and cavitation in comminuting residual fragments during shock wave lithotripsy (SWL), cylindrical 4 × 4 mm BegoStone phantoms were treated in an electromagnetic lithotripter either at the focus (z = 0, p+ = ∼45 MPa) or pre-focally (z = −30 mm, p+ = ∼24 MPa). The treatment was performed with the stone immersed either in degassed water or in Butanediol, which has similar acoustic impedance to water but much higher viscosity to suppress cavitation. At the focus, the first fracture was observed after 26 ± 9 shocks, both in water and Butanediol (p = 0.7). However, when stones were moved pre-focally where comparable cavitation is produced (based on high speed imaging), the average shock number required for the initial fracture was increased to 66 ± 10 in water and 122 ± 20 in Butanediol (p = 0.002). Below −40 mm prefocally (p+

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.

We will present a computational model of the focusing of an electromagnetically induced pressure pulse by an acoustic lens and subsequent shock wave formation. Linear elasticity equations for the lens are solved simultaneously with Euler hydrodynamic equations for water considered to be a compressible medium with a Tait equation of state. The adaptive mesh refinement model allows both three‐dimensional and two‐dimensional axisymmetric computations. A number of coupling approaches at the lens‐water interface are investigated by comparison to experimental results: transfer only of pressure boundary condition, coupling of displacement velocities, and a buffer linear elasticity region in the water immediately adjacent to lens. The model is validated against single‐medium measurements (water or lens material), and the complete experimental shock wave formation process. Initial results from a crack propagation model in stone simulants placed at the lithotripter focus will also be presented.

The third‐generation electromagnetic (EM) shock wave lithotripters often have narrow focal width and high‐peak pressure compared to the original HM‐3. In addition, the pressure waveform produced by a typical EM lithotripter has a secondary compressive wave that suppresses lithotripter pulse induced cavitation, which is an important mechanism for stone comminution. These features have been contributed to the reduced effectiveness of the modern EM lithotripters. To overcome these drawbacks, we have designed a new acoustic lens for the Siemens Modularis EM lithotripter that produces an idealized pressure waveform similar to the HM‐3 with broad focal width and low‐peak pressure. At acoustic pulse energy of 53 mJ, the new lens design enlarges the −6 dB focal width of the Modularis by 47% while significantly reducing the second compressive wave throughout its focal plane. After 2000 shocks, in vitro comminution produced by the original and new lens designs are 100% and 99% at the lithotripter focus, and (49.7±15.0)% and (75.3±8.74)% (p < 0.001) at 10 mm off axis, respectively. Corresponding values in vivo are (63.4±17.4)% and (83.3±8.5)% (p < 0.01), demonstrating the significant performance improvement provided by the new lens design. [Work supported by NIH Grant Nos. R01DK052985 and S10RR016802.]

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...