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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.

The penetration depth of photoacoustic imaging in biological tissues has been fundamentally limited by the strong optical attenuation when light is delivered externally through the tissue surface. To address this issue, we previously reported internal-illumination photoacoustic imaging using a customized radial-emission optical fiber diffuser, which, however, has complex fabrication, high cost, and non-uniform light emission. To overcome these shortcomings, we have developed a new type of low-cost fiber diffusers based on a graded-scattering method in which the optical scattering of the fiber diffuser is gradually increased as the light travels. The graded scattering can compensate for the optical attenuation and provide relatively uniform light emission along the diffuser. We performed Monte Carlo numerical simulations to optimize several key design parameters, including the number of scattering segments, scattering anisotropy factor, divergence angle of the optical fiber, and reflective index of the surrounding medium. These optimized parameters collectively result in uniform light emission along the fiber diffuser and can be flexibly adjusted to accommodate different applications. We fabricated and characterized the prototype fiber diffuser made of agarose gel and intralipid. Equipped with the new fiber diffuser, we performed thorough proof-of-concept studies on ex vivo tissue phantoms and an in vivo swine model to demonstrate the deep-imaging capability (~10 cm achieved ex vivo) of photoacoustic tomography. We believe that the internal light delivery via the optimized fiber diffuser is an effective strategy to image deep targets (e.g., kidney) in large animals or humans.

Purpose: Although cavitation during laser lithotripsy (LL) contributes to the Moses effect, the impact of cavitation on stone damage is less clear. Using different laser settings, we investigate the role of cavitation bubbles in energy delivery and stone damage. Materials and Methods: The role of cavitation in laser energy delivery was characterized by using photodetector measurements synced with high-speed imaging for laser pulses of varying durations. BegoStone samples were treated with the laser fiber oriented perpendicularly in contact with the stone in water or in air to assess the impact of cavitation on crater formation. Crater volume and geometry were quantified by using optical coherence tomography. Further, the role of cavitation in stone damage was elucidated by treatment in water with the fiber oriented parallel to the stone surface and by photoelastic imaging. Results: Longer pulse durations resulted in higher energy delivery but smaller craters. Stones treated in water resulted in greater volume, wider yet shallower craters compared with those treated in air. Stones treated with the parallel fiber showed crater formation after 15 pulses, confirmed by high-speed imaging of the bubble collapse with the resultant stress field captured by photoelastic imaging. Conclusions: Despite improved energy delivery, the longer pulse mode produced smaller crater volume, suggesting additional processes secondary to photothermal ablation are involved in stone damage. Our critical observations of the difference in stone damage treated in water vs in air, combined with the crater formation by parallel fiber, suggest that cavitation is a contributor to stone damage during LL.

Temperature mapping is essential in many biomedical studies and interventions to precisely control the tissue’s thermal conditions for optimal treatment efficiency and minimal side effects. Based on the Grüneisen parameter’s temperature dependence, photoacoustic (PA) imaging can provide relative temperature measurement, but it has been traditionally challenging to measure absolute temperatures without knowing the baseline temperature, especially in deep tissues with unknown optical and acoustic properties. Here, we report a new thermal-energy-memory-based photoacoustic thermometry (TEMPT). By illuminating the tissue with a burst of nanosecond laser pulses, TEMPT exploits the temperature dependence of the thermal energy lingering, which is probed by the corresponding PA signals acquired within the thermal confinement. A self-normalized ratiometric measurement cancels out temperature-irrelevant quantities and estimates the Grüneisen parameter. The temperature can then be evaluated, given the tissue’s temperature-dependent Grüneisen parameter, mass density, and specific heat capacity. Unlike the conventional PA thermometry, TEMPT does not require the knowledge of tissue’s baseline temperature, nor the optical properties. We have developed a mathematical model to describe the temperature dependence in TEMPT. We have demonstrated the feasibility of the temperature evaluation on tissue phantoms at 1.5 cm depth within a clinically relevant temperature range. Finally, as proof-of-concept, we applied TEMPT for temperature mapping during focused ultrasound treatment in mice in vivo at 2 mm depth. As a generic temperature mapping method, TEMPT is expected to find applications in thermotherapy of cancers on small animal models.

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.

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.

The Nanopulse Lithotripter (NPL; Lithotech Medical, Israel) is a novel intracorporeal device that uses a nanosecond duration electrical discharge through a reusable flexible coaxial probe to endoscopically fragment urinary stones. This device was compared with a holmium laser lithotripsy (HoL) with regard to stone fragmentation efficiency (SFE) and its impact on flexible ureteroscope (URS) deflection and flow of irrigation.Using a custom bench model, a 6 mm BegoStone cylindrical phantom (mixture 5:2) was confined under 0.9% saline atop sequential mesh sieves. The SFE of two NPL probe sizes (2.0F, 3.6F) and two HoL fibers (200, 365 μm) was evaluated using concordant settings of 1 J and 5 Hz. URS deflection and irrigation flow with NPL probes in the working channel were tested in five new fourth generation flexible URS and compared with other adjunct endourologic instruments.The 2.0F NPL showed improved SFE compared with the 200 μm laser (86 mg/min vs 52 mg/min, p = 0.014) as did the 3.6F NPL vs the 365 μm laser (173 mg/min vs 80 mg/min, p = 0.05). The NPL created more 1 to 2 mm fragments; the laser created more dust. URS deflection reduced by 3.75° with the 2.0 NPL probe. URS irrigation flow reduced from 36.5 to 6.3 mL/min with the 2.0F NPL probe.NPL shows improved SFE compared with HoL. Flow with the 2.0F probe is akin to a stone basket. NPL offers an effective alternative to HoL.

INTRODUCTION AND OBJECTIVES: A new intracorporeal lithotriptor uses a nanosecond duration electrical discharge through a flexible coaxial probe to endoscopically fragment urinary stones. This device was compared to a holmium laser with regards to stone fragmentation efficiency and their impact on flexible ureteroscope deflection and flow of irrigation. METHODS: Using a custom bench model, stone fragmentation efficiency of the Nano-electric Pulse Lithotriptor (NPL, Lithotech Group, Israel) was evaluated with a begostone (mixture 5:2) confined under 0.9% normal saline atop sequential mesh sieves. Two NPL probe sizes (2.0 and 3.6F) and two holmium laser fibers (200 mm and 365mm) were evaluated using 6mm begostones. Time to first break, time to complete break (all fragments

In this study, a foam mask is introduced to elongate the beam width in the focal plane of a shock wave lithotripter, and a respiration gating beam steering strategy is proposed to accurately target stones, which are movable because of patient respiratory motion, radiation force, hydraulics, gravity, etc. The mask is steered to revolve the elongated elliptical focal zone of the acoustic field, so as to cover as much as possible the stone moving area. The beam steering strategy provides the most opportunity to deliver the shock wave energy straightly on the moving stones but not to the peripheral tissues, enhancing the stone fracture efficacy whilst reducing tissue injury. Simulation results with specific stone motion models are given to proof the advantages of the elongated focal zone in tracking stone target, and show that the stone overlap in the focal zone is improved significantly and competitively with the beam steering strategy, compared with no beam steering.

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.

To elucidate mechanisms of cavitation action on a surface with microcapillary discontinuity and refine the model of the sonocapillary effect, the force acting on a cylinder is correlated with the height of a liquid in the capillary under cavitation, both quantities being measured at the same point of the ultrasonic field. It is found that the force acting on the cylinder is directed toward a cavitation cluster stabilized at the end face of the cylinder. This force can be enhanced with another cylinder placed on the side of the cluster coaxially with the first one. The dynamics of the cavitation cluster depending on the cylinder spacing is investigated in the case when one of the cylinders is on a pendulum suspension. The conditions for self-sustained oscillations of the pendulum are found. The dependence of the attracting force between the cylinders on the ultrasonic frequency and cylinder spacing is derived. The end-face-averaged pressure exerted on a cylinder of diameter 1.2 mm may reach 0.16 kPa, and the intracapillary pressure attains 0.89 kPa. Thus, the sonocapillary effect may be explained, at least partially, by a counterpressure arising from cluster-capillary interaction. This effect can be used in designing cavitation sensors and ultrasonic sources.

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 application of an electric discharge at numerous holes in a dielectric diaphragm for generating spherically focused shock waves in a salt solution is described. The design of the presented transducer makes the erosion of the electrodes impossible, since they are placed beyond the discharge zone; as a result, the point of focus stabilizes. The dependences on the discharge voltage, the number and total area of the holes in the diaphragm, and the electrolyte concentration are obtained for the pressure-wave amplitude at the focus; the extreme values are ∼40 and –12 MPa in the compression and rarefaction waves, respectively. The possibility of comminuting stones with masses of

Nonlinear processes accompanying the focusing of a microsecond acoustic pulse produced by an electromagnetic source shaped as a spherical segment are investigated. The processes are considered to be far from the boundaries of a liquid, in the absence of cavitation. Detailed measurements of the pressure field by a fiber-optic sensor and high-speed photography of the shock front are performed. The pressure field is found to be determined by the nonlinear effects that occur in the course of the propagation of the initial converging compression wave and an edge rarefaction wave. The peak pressure amplitudes at the focus are 75 and −42 MPa for the compression and rarefaction waves, respectively, at the maximum voltage of the pulse generator in use. The measured length of the compression wave front is equal to the response time of the sensor (8 ns). The pressure amplitude is shown to be limited by the irregularity of the propagation of a shock wave in the form of Mach’s disk. At the focus, the pressure gradient across the radiator axis reaches 0.5 atm/μm, while the diameter of the focal spot is 2.5±0.2 mm. The focus of the edge rarefaction wave formed due to diffraction is located closer to the radiator than the focus of the compression wave, which may facilitate the study of the biological effect of cavitation independently of the shear motion of the medium.

The efficiency of shock wave lithotripsy (SWL), a noninvasive first-line therapy for millions of nephrolithiasis patients, has not improved substantially in the past two decades, especially in regard to stone clearance. Here, we report a new acoustic lens design for a contemporary electromagnetic (EM) shock wave lithotripter, based on recently acquired knowledge of the key lithotripter field characteristics that correlate with efficient and safe SWL. The new lens design addresses concomitantly three fundamental drawbacks in EM lithotripters, namely, narrow focal width, nonidealized pulse profile, and significant misalignment in acoustic focus and cavitation activities with the target stone at high output settings. Key design features and performance of the new lens were evaluated using model calculations and experimental measurements against the original lens under comparable acoustic pulse energy (E+) of 40 mJ. The −6-dB focal width of the new lens was enhanced from 7.4 to 11 mm at this energy level, and peak pressure (41 MPa) and maximum cavitation activity were both realigned to be within 5 mm of the lithotripter focus. Stone comminution produced by the new lens was either statistically improved or similar to that of the original lens under various in vitro test conditions and was significantly improved in vivo in a swine model (89% vs. 54%, P = 0.01), and tissue injury was minimal using a clinical treatment protocol. The general principle and associated techniques described in this work can be applied to design improvement of all EM lithotripters.

The dynamics of luminescence generation and cavitation in the field of spherically focused and plane shock-acoustic waves in water, glycerin, and their mixtures is studied. It is shown that in the spherical focusing of shock-acoustic waves, the first pulse of luminescence correlates with cavitational rupture of the liquid. It is assumed that the registered luminescence is caused by electrokinetic processes upon formation and growth of cavitational bubbles.

The acoustic lens of the Modularis electromagnetic shock wave lithotripter (Siemens, Malvern, Pennsylvania) was modified to produce a pressure waveform and focal zone more closely resembling that of the original HM3 device (Dornier Medtech, Wessling, Germany). We assessed the newly designed acoustic lens in vivo in an animal model.Stone fragmentation and tissue injury produced by the original and modified lenses of the Modularis lithotripter were evaluated in a swine model under equivalent acoustic pulse energy (about 45 mJ) at 1 Hz pulse repetition frequency. Stone fragmentation was determined by the weight percent of stone fragments less than 2 mm. To assess tissue injury, shock wave treated kidneys were perfused, dehydrated, cast in paraffin wax and sectioned. Digital images were captured every 120 μm and processed to determine functional renal volume damage.After 500 shocks, the mean ± SD stone fragmentation efficiency produced by the original and modified lenses was 48% ± 12% and 52% ± 17%, respectively (p = 0.60). However, after 2,000 shocks, the modified lens showed significantly improved stone fragmentation compared to the original lens (mean 86% ± 10% vs 72% ± 12%, p = 0.02). Tissue injury caused by the original and modified lenses was minimal at a mean of 0.57% ± 0.44% and 0.25% ± 0.25%, respectively (p = 0.27).With lens modification the Modularis lithotripter demonstrates significantly improved stone fragmentation with minimal tissue injury at a clinically relevant acoustic pulse energy. This new lens design could potentially be retrofitted to existing lithotripters, improving the effectiveness of electromagnetic lithotripters.

An experimental system for digital stereoscopic imaging produced by using a high-speed color camera is described. Two bright-field image projections of a three-dimensional object are captured utilizing additive-color backlighting (blue and red). The two images are simultaneously combined on a two-dimensional image sensor using a set of dichromatic mirrors, and stored for off-line separation of each projection. This method has been demonstrated in analyzing cavitation bubble dynamics near boundaries. This technique may be useful for flow visualization and in machine vision applications.

The performance of a newly developed light spot hydrophone (LSHD) in lithotripter field characterization was compared to that of the fiber optic probe hydrophone (FOPH). Pressure waveforms produced by a stable electromagnetic shock wave source were measured by the LSHD and FOPH under identical experimental conditions. In the low energy regime, focus and field acoustic parameters matched well between the two hydrophones. At clinically relevant high energy settings for shock wave lithotripsy, the measured leading compressive pressure waveforms matched closely with each other. However, the LSHD recorded slightly larger |P–| (p < 0.05) and secondary peak compressive pressures (p < 0.01) than the FOPH, leading to about 20% increase in total acoustic pulse energy calculated in a 6 mm radius around the focus (p = 0.06). Tensile pulse durations deviated ∼5% (p < 0.01) due to tensile wave shortening from cavitation activity using the LSHD. Intermittent compression spikes and laser light reflection artifacts have been correlated to bubble activity based on simultaneous high-speed imaging analysis. Altogether, both hydrophones are adequate for lithotripter field characterization as specified by the international standard IEC 61846.

Previous studies have demonstrated that treatment strategy plays a critical role in ensuring maximum stone fragmentation during shockwave lithotripsy (SWL). We aimed to develop an optimal treatment strategy in SWL to produce maximum stone fragmentation.Four treatment strategies were evaluated using an in-vitro experimental setup that mimics stone fragmentation in the renal pelvis. Spherical stone phantoms were exposed to 2100 shocks using the Siemens Modularis (electromagnetic) lithotripter. The treatment strategies included increasing output voltage with 100 shocks at 12.3 kV, 400 shocks at 14.8 kV, and 1600 shocks at 15.8 kV, and decreasing output voltage with 1600 shocks at 15.8 kV, 400 shocks at 14.8 kV, and 100 shocks at 12.3 kV. Both increasing and decreasing voltages models were run at a pulse repetition frequency (PRF) of 1 and 2 Hz. Fragmentation efficiency was determined using a sequential sieving method to isolate fragments less than 2 mm. A fiberoptic probe hydrophone was used to characterize the pressure waveforms at different output voltage and frequency settings. In addition, a high-speed camera was used to assess cavitation activity in the lithotripter field that was produced by different treatment strategies.The increasing output voltage strategy at 1 Hz PRF produced the best stone fragmentation efficiency. This result was significantly better than the decreasing voltage strategy at 1 Hz PFR (85.8% vs 80.8%, P=0.017) and over the same strategy at 2 Hz PRF (85.8% vs 79.59%, P=0.0078).A pretreatment dose of 100 low-voltage output shockwaves (SWs) at 60 SWs/min before increasing to a higher voltage output produces the best overall stone fragmentation in vitro. These findings could lead to increased fragmentation efficiency in vivo and higher success rates clinically.

The 3rd‐generation electromagnetic (EM) shock wave lithotripters often have narrow focal width and high peak pressure compared to the original Dornier HM‐3. In addition, the pressure waveform produced by a typical EM lithotripter has a secondary compressive wave following the tensile component that suppresses lithotripter pulse induced cavitation, which may impact negatively on stone comminution. These characteristic changes in the modern EM lithotripters may contribute in part to their reduced effectiveness observed clinically. To overcome these two drawbacks, we have designed a new acoustic lens for the Siemens Modularis EM lithotripter that produces an idealized pressure waveform similar to that of 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 in the lithotripter pulse throughout its focal plane. After 2000 shocks, in vitro commi...

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.

The effect of beam size on stone comminution in the Dornier HM‐3 lithotripter were investigated using a modified reflector (MR), which was developed to produce an acoustic field with higher peak pressure and smaller beam size compared to the original reflector (OR) of the HM‐3. The acoustic fields produced at 20 kV by the MR in the focal plane, and by the OR in the focal and pre‐focal plane (z = −15 mm) were characterized using a light spot hydrophone. The efficiencies of stone comminution in a mesh holder were similar, but the corresponding values produced by using the MR in a membrane holder were significantly lower than those produced by the OR in the focal and pre‐focal planes. These results suggest that a broad beam size could increase stone comminution efficiency when fragments are spreading out or moving due to respiratory motion in a large area during SWL. In contrast, when stone fragments are confined and well aligned to lithotripter focus the beam size may not influence significantly the treatme...

The focusing of laser-generated shock waves by a truncated ellipsoidal reflector was experimentally and numerically investigated. Pressure waveform and distribution around the first (F(1)) and second foci (F(2)) of the ellipsoidal reflector were measured. A neodymium doped yttrium aluminum garnet laser of 1046 nm wavelength and 5 ns pulse duration was used to create an optical breakdown at F(1), which generates a spherically diverging shock wave with a peak pressure of 2.1-5.9 MPa at 1.1 mm stand-off distance and a pulse width at half maximum of 36-65 ns. Upon reflection, a converging shock wave is produced which, upon arriving at F(2), has a leading compressive wave with a peak pressure of 26 MPa and a zero-crossing pulse duration of 0.1 mus, followed by a trailing tensile wave of -3.3 MPa peak pressure and 0.2 mus pulse duration. The -6 dB beam size of the focused shock wave field is 1.6 x 0.2 mm(2) along and transverse to the shock wave propagation direction. Formation of elongated plasmas at high laser energy levels limits the increase in the peak pressure at F(2). General features in the waveform profile of the converging shock wave are in qualitative agreement with numerical simulations based on the Hamilton model.

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 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.

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.

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.

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 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. ...

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...