Shock waves generated by toroidal bubble collapse are imperative for kidney stone dusting during Holmium:YAG laser lithotripsy.

Holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy (LL) has been the treatment of choice for kidney stone disease for more than two decades, yet the mechanisms of action are not completely clear. Besides photothermal ablation, recent evidence suggests that cavitation bubble collapse is pivotal in kidney stone dusting when the Ho:YAG laser operates at low pulse energy (Ep) and high frequency (F). In this work, we perform a comprehensive series of experiments and model-based simulations to dissect the complex physical processes in LL. Under clinically relevant dusting settings (Ep = 0.2 J, F = 20 Hz), our results suggest that majority of the irradiated laser energy (>90 %) is dissipated by heat generation in the fluid surrounding the fiber tip and the irradiated stone surface, while only about 1 % may be consumed for photothermal ablation, and less than 0.7 % is converted into the potential energy at the maximum bubble expansion. We reveal that photothermal ablation is confined locally to the laser irradiation spot, whereas cavitation erosion is most pronounced at a fiber tip-stone surface distance about 0.5 mm where multi foci ring-like damage outside the thermal ablation zone is observed. The cavitation erosion is caused by the progressively intensified collapse of jet-induced toroidal bubble near the stone surface (<100 µm), as a result of Raleigh-Taylor and Richtmyer-Meshkov instabilities. The ensuing shock wave-stone interaction and resultant leaky Rayleigh waves on the stone surface may lead to dynamic fatigue and superficial material removal under repeated bombardments of toroidal bubble collapses during dusting procedures in LL.

Dissimilar cavitation dynamics and damage patterns produced by parallel fiber alignment to the stone surface in holmium:yttrium aluminum garnet laser lithotripsy.

Recent studies indicate that cavitation may play a vital role in laser lithotripsy. However, the underlying bubble dynamics and associated damage mechanisms are largely unknown. In this study, we use ultra-high-speed shadowgraph imaging, hydrophone measurements, three-dimensional passive cavitation mapping (3D-PCM), and phantom test to investigate the transient dynamics of vapor bubbles induced by a holmium:yttrium aluminum garnet laser and their correlation with solid damage. We vary the standoff distance (SD) between the fiber tip and solid boundary under parallel fiber alignment and observe several distinctive features in bubble dynamics. First, long pulsed laser irradiation and solid boundary interaction create an elongated "pear-shaped" bubble that collapses asymmetrically and forms multiple jets in sequence. Second, unlike nanosecond laser-induced cavitation bubbles, jet impact on solid boundary generates negligible pressure transients and causes no direct damage. A non-circular toroidal bubble forms, particularly following the primary and secondary bubble collapses at SD = 1.0 and 3.0 mm, respectively. We observe three intensified bubble collapses with strong shock wave emissions: the intensified bubble collapse by shock wave, the ensuing reflected shock wave from the solid boundary, and self-intensified collapse of an inverted "triangle-shaped" or "horseshoe-shaped" bubble. Third, high-speed shadowgraph imaging and 3D-PCM confirm that the shock origins from the distinctive bubble collapse form either two discrete spots or a "smiling-face" shape. The spatial collapse pattern is consistent with the similar BegoStone surface damage, suggesting that the shockwave emissions during the intensified asymmetric collapse of the pear-shaped bubble are decisive for the solid damage.

Intercellular Calcium Waves and Permeability Change Induced by Vertically Deployed Surface Acoustic Waves in a Human Cerebral Microvascular Endothelial Cell Line (hCMEC/D3) Monolayer.

OBJECTIVE: The ultrasound-mediated blood-brain barrier (BBB) opening with microbubbles has been widely employed, while recent studies also indicate the possibility that ultrasound alone can open the BBB through a direct mechanical effect. However, the exact mechanisms through which ultrasound interacts with the BBB and whether it can directly trigger intracellular signaling and a permeability change in the BBB endothelium remain unclear. METHODS: Vertically deployed surface acoustic waves (VD-SAWs) were applied on a human cerebral microvascular endothelial cell line (hCMEC/D3) monolayer using a 33-MHz interdigital transducer that exerts shear stress-predominant stimulation. The intracellular calcium response was measured by fluorescence imaging, and the permeability of the hCMEC/D3 monolayer was assessed by transendothelial electrical resistance (TEER). DISCUSSION: At a certain intensity threshold, VD-SAWs induced an intracellular calcium surge that propagated to adjacent cells as intercellular calcium waves. VD-SAWs induced a TEER decrease in a pulse repetition frequency-dependent manner, thereby suggesting possible involvement of the mechanosensitive ion channels. CONCLUSION: The unique VD-SAW system enables more physiological mechanical stimulation of the endothelium monolayer. Moreover, it can be easily combined with other measurement devices, providing a useful platform for further mechanistic studies on ultrasound-mediated BBB opening.

The Effects of Scanning Speed and Standoff Distance of the Fiber on Dusting Efficiency during Short Pulse Holmium: YAG Laser Lithotripsy.

To investigate the effects of fiber lateral scanning speed across the stone surface (vfiber) and fiber standoff distance (SD) on dusting efficiency during short pulse holmium (Ho): YAG laser lithotripsy (LL), pre-soaked BegoStone samples were treated in water using 0.2 J/20 Hz at SD of 0.10~0.50 mm with vfiber in the range of 0~10 mm/s. Bubble dynamics, pressure transients, and stone damage were analyzed. To differentiate photothermal ablation vs. cavitation damage, experiments were repeated in air, or in water with the fiber tip at 0.25 mm proximity from the ureteroscope end to mitigate cavitation damage. At SD = 0.10 mm, the maximum dusting efficiency was produced at vfiber = 3.5 mm/s, resulting in long (17.5 mm), shallow (0.15 mm), and narrow (0.4 mm) troughs. In contrast, at SD = 0.50 mm, the maximum efficiency was produced at vfiber = 0.5 mm/s, with much shorter (2.5 mm), yet deeper (0.35 mm) and wider (1.4 mm), troughs. With the ureteroscope end near the fiber tip, stone damage was significantly reduced in water compared to those produced without the ureteroscope. Under clinically relevant vfiber (1~3 mm/s), dusting at SD = 0.5 mm that promotes cavitation damage may leverage the higher frequency of the laser (e.g., 40 to 120 Hz) and, thus, significantly reduces the procedure time, compared to at SD = 0.1 mm that promotes photothermal ablation. Dusting efficiency during short pulse Ho: YAG LL may be substantially improved by utilizing an optimal combination of vfiber, SD, and frequency.

Cavitation Plays a Vital Role in Stone Dusting During Short Pulse Holmium:YAG Laser Lithotripsy.

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.

Variations of stress field and stone fracture produced at different lateral locations in a shockwave lithotripter field.

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.

Optimal pulse length of insonification for Piezo1 activation and intracellular calcium response.

Ultrasound (US) neuromodulation, especially sonogenetics, has been demonstrated with potential applications in noninvasive and targeted treatment of various neurological disorders. Despite the growing interest, the mechanism for US neuromodulation remains elusive, and the optimal condition for eliciting a neural response with minimal adverse effect has not been identified. Here, we investigate the Piezo1 activation and intracellular calcium response elicited by acoustical streaming induced shear stress under various US exposure conditions. We find that Piezo1 activation and resultant intracellular calcium response depend critically on shear stress amplitude and pulse length of the stimulation. Under the same insonification acoustic energy, we further identify an optical pulse length that leads to maximum cell deformation, Piezo1 activation, and calcium response with minimal injury, confirmed by numerical modeling of Piezo1 channel gating dynamics. Our results provide insight into the mechanism of ultrasonic activation of Piezo1 and highlight the importance of optimizing US exposure conditions in sonogenetics applications.

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.