The Role of Cavitation in Energy Delivery and Stone Damage During Laser Lithotripsy.

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.

Experimentally validated multiphysics computational model of focusing and shock wave formation in an electromagnetic lithotripter.

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.

Stereoscopic high-speed imaging using additive colors.

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.

Focusing of shock waves induced by optical breakdown in water.

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.

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model.

BACKGROUND: High intensity focused ultrasound (HIFU) is an emerging non-invasive treatment modality for localized treatment of cancers. While current clinical strategies employ HIFU exclusively for thermal ablation of the target sites, biological responses associated with both thermal and mechanical damage from focused ultrasound have not been thoroughly investigated. In particular, endogenous danger signals from HIFU-damaged tumor cells may trigger the activation of dendritic cells. This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment. METHODS: Mice bearing MC-38 colon adenocarcinoma tumors were treated with thermal and mechanical HIFU exposure settings in order to independently observe HIFU-induced effects on the host's immunological response. In vivo dendritic cell activity was assessed along with the host's response to challenge tumor growth. RESULTS: Thermal and mechanical HIFU were found to increase CD11c+ cells 3.1-fold and 4-fold, respectively, as compared to 1.5-fold observed for DC injection alone. In addition, thermal and mechanical HIFU increased CFSE+ DC accumulation in draining lymph nodes 5-fold and 10-fold, respectively. Moreover, focused ultrasound treatments not only caused a reduction in the growth of primary tumors, with tumor volume decreasing by 85% for thermal HIFU and 43% for mechanical HIFU, but they also provided protection against subcutaneous tumor re-challenge. Further immunological assays confirmed an enhanced CTL activity and increased tumor-specific IFN-gamma-secreting cells in the mice treated by focused ultrasound, with cytotoxicity induced by mechanical HIFU reaching as high as 27% at a 10:1 effector:target ratio. CONCLUSION: These studies present initial encouraging results confirming that focused ultrasound treatment can elicit a systemic anti-tumor immune response, and they suggest that this immunity is closely related to dendritic cell activation. Because DC activation was more pronounced when tumor cells were mechanically lysed by focused ultrasound treatment, mechanical HIFU in particular may be employed as a potential strategy in combination with subsequent thermal ablations for increasing the efficacy of HIFU cancer treatment by enhancing the host's anti-tumor immunity.

Interaction of lithotripter shockwaves with single inertial cavitation bubbles.

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.

Assessment of shock wave lithotripters via cavitation potential.

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.