Signatures of microstreaming patterns induced by non-spherically oscillating bubbles.

In this study, we report recent theoretical and experimental developments dealing with the axisymmetric flow surrounding non-spherically oscillating microbubbles. A wide variety of microstreaming patterns is revealed using a theoretical modeling providing exact analytical solutions of the second-order mean flows. The streaming pattern is highly dependent on the modal content of the bubble interface oscillation, including possibly spherical, translational, and nonspherical modes, as well as any combination of these modes.

Induction of Microstreaming by Nonspherical Bubble Oscillations in an Acoustic Levitation System.

When located near biological barriers, oscillating microbubbles may increase cell membrane permeability, allowing for drug and gene internalization. Experimental observations suggest that the temporary permeabilization of these barriers may be due to shear stress that is exerted on cell tissues by cavitation microstreaming. Cavitation microstreaming is the generation of vortex flows which arise around oscillating ultrasound microbubbles.

Acoustic microstreaming produced by nonspherical oscillations of a gas bubble. IV. Case of modes n and m.

This paper is the conclusion of work done in our previous papers [A. A. Doinikov et al.

TRPV4 promotes acoustic wave-mediated BBB opening via Ca/PKC-δ pathway.

Introduction: Numerous studies have shown the ability of low-energy acoustic waves such as focused ultrasound or shockwave to transiently open blood-brain barrier (BBB) and facilitate drug delivery to the brain. Preclinical and clinical evidences have well demonstrated the efficacy and safety in treating various brain disorders. However, the molecular mechanisms of acoustic waves on the BBB are still not fully understood.

Secondary radiation force between two closely spaced acoustic bubbles.

Two acoustic bubbles may attract or repel due to the secondary radiation force acting on them. We use here a dual-frequency levitation chamber in order to trap two oscillating microbubbles at close, fixed distance, and to perform measurements of the interaction force. We successfully compare our measurements to a commonly used theoretical model that assumes linear spherical oscillations, and disregards attenuation and multiple scattering between bubbles.

Nonspherical modes nondegeneracy of a tethered bubble.

When excited at sufficiently high acoustic pressures, a wall-attached bubble may exhibit asymmetric nonspherical modes. These vibration modes can be decomposed over the set of spherical harmonics Y_{nm}(θ,ϕ) for a degree n and order m. We experimentally capture the time-resolved dynamics of asymmetric bubble oscillations in a top-view configuration.

A Single High-Intensity Shock Wave Pulse With Microbubbles Opens the Blood-Brain Barrier in Rats.

Focused extracorporeal shockwave (FSW), one kind of focused high-intensity pulsed ultrasound, has been shown to induce blood-brain barrier (BBB) opening in targeted brain areas in rat animal models with minimal detrimental effects below threshold intensity levels or iterations. In the current study, we found that the thresholds could be further reduced by the addition of microbubbles (ultrasound contrast agents or UCA; SonoVue). FSW with 2 × 10 MBs/kg of UCA (20% of clinical dosage) at an intensity level of 0.

Acoustic microstreaming produced by nonspherical oscillations of a gas bubble. III. Case of self-interacting modes n-n.

This paper is the continuation of work done in our previous papers [A. A. Doinikov et al.

Subharmonic spherical bubble oscillations induced by parametric surface modes.

A potential source of subharmonic bubble emissions is revealed experimentally by high-speed imaging. When an acoustic bubble is driven at sufficiently large pressure amplitudes, energy transfer from surface to volume oscillations can lead to the triggering of subharmonic spherical oscillations. This experimental evidence is in agreement with recent theoretical modeling of nonspherical bubble dynamics accounting for nonlinear mode coupling.

Confocal lens focused piezoelectric lithotripter.

This work focuses on the evaluation of a type of piezoelectric lithotripter with similar dimensions of a commercial lithotripter and composed of either 3 or 4 large lens focused piezoelectric transducers set either in a confocal coplanar C-shape or a confocal spherical shape. Each transducer is made with a 92 mm diameter 220 kHz flat piezoelectric ceramic disc and a 3D printed acoustic lens. Both confocal setups pressure field were measured with a fiber optic hydrophone, and in vitro fragmentations of 13 mm diameter and 14 mm length cylindrical model stones were done in a 2 mm mesh basket.

Acoustic microstreaming produced by nonspherical oscillations of a gas bubble. II. Case of modes 1 and m.

This paper continues a study that was started in our previous paper [A. A. Doinikov et al.

Acoustic microstreaming produced by nonspherical oscillations of a gas bubble. I. Case of modes 0 and m.

A theory is developed that allows one to model the velocity field of acoustic microstreaming produced by nonspherical oscillations of an acoustically driven gas bubble. It is assumed that some of the bubble oscillation modes are excited parametrically and hence can oscillate at frequencies different from the driving frequency. Analytical solutions are derived in terms of complex amplitudes of oscillation modes, which means that the mode amplitudes are assumed to be known and serve as input data when the velocity field of acoustic microstreaming is calculated.

Contrast Agent Microbubble Jetting during Initial Interaction with 200-kHz Focused Ultrasound.

The initial response of microbubbles flowing through a 500-μm polycarbonate capillary to a burst of 200-kHz focused ultrasound, at peak-negative pressure amplitudes from 0.7-1.5 MPa, was investigated with dual-perspective high-speed imaging.

Safety evaluation of frequent application of microbubble-enhanced focused ultrasound blood-brain-barrier opening.

Focused ultrasound (FUS) with the presence of microbubbles induces blood brain barrier (BBB) opening in targeted areas and facilitates drug delivery. However, recent studies have indicated that FUS-BBB opening with excessive exposure levels may be associated with inflammatory response and cellular/tissue damage. Multiple weekly FUS exposures have been shown to be safe for human subjects.

Ultrafast monitoring and control of subharmonic emissions of an unseeded bubble cloud during pulsed sonication.

In the aim of limiting the destructive effects of collapsing bubbles, the regime of stable cavitation activity is currently targeted for sensitive therapeutic applications such as blood-brain barrier opening by ultrasound. This activity is quantified through the emergence of the subharmonic component of the fundamental frequency. Due to the intrinsically stochastic behavior of the cavitation phenomenon, a better control of the different (stable or inertial) cavitation regimes is a key requirement in the understanding of the mechanisms involving each bubble-induced mechanical effect.

Focused shockwave induced blood-brain barrier opening and transfection.

Despite extensive efforts in recent years, the blood-brain barrier (BBB) remains a significant obstacle for drug delivery. This study proposes using a clinical extracorporeal shockwave instrument to open the BBB, combined with a laser assisted bi-axial locating platform to achieve non-invasive, controllable-focus and reversible BBB opening in the brains of rats. Under shockwave treatment with an intensity level of 5 (P9.

Dynamics of nonspherical microbubble oscillations above instability threshold.

Time-resolved dynamics of nonspherical oscillations of micrometer-sized bubbles are captured and analyzed using high-speed imaging. The axisymmetry of the bubble shape is ensured with certainty for the first time from the recordings of two synchronous high-speed cameras located at 90^{∘}. The temporal dynamics of finite-amplitude nonspherical oscillations are then analyzed for various acoustic pressures above the instability threshold.

Accompanying the frequency shift of the nonlinear resonance of a gas bubble using a dual-frequency excitation.

An asymptotic method is applied to analyze the nonlinear oscillations of a gas bubble driven by a dual-frequency excitation. More specifically, the latter is considered as a combination of two neighboring, incommensurate frequencies and is treated as a nonstationary excitation. This implies that both amplitude and phase of the bubble response are slowly oscillating at the time scale of the frequency difference, thus leading to a regime of aperiodic oscillations.

A derivation of the stable cavitation threshold accounting for bubble-bubble interactions.

The subharmonic emission of sound coming from the nonlinear response of a bubble population is the most used indicator for stable cavitation. When driven at twice their resonance frequency, bubbles can exhibit subharmonic spherical oscillations if the acoustic pressure amplitude exceeds a threshold value. Although various theoretical derivations exist for the subharmonic emission by free or coated bubbles, they all rest on the single bubble model.

Experimental evidence of nonlinear mode coupling between spherical and nonspherical oscillations of microbubbles.

We report observations of strong nonlinear interactions between the spherical, translational, and shape oscillations of micrometer-size bubbles. This is achieved through high-speed recordings of single bubble dynamics driven by amplitude-modulated ultrasound. The features of mode coupling are highlighted through (i) the exponential growth of the parametrically excited mode (n=3) triggered by the spherical oscillations followed by a saturation due to energy transfer towards the translation and even modes, (ii) the excitation of modes well below their parametric pressure threshold, and (iii) clear modification of the breathing mode R(t).

Hysteresis of inertial cavitation activity induced by fluctuating bubble size distribution.

Amongst the variety of complex phenomena encountered in nonlinear physics, a hysteretic effect can be expected on ultrasound cavitation due to the intrinsic nonlinearity of bubble dynamics. When applying successive ultrasound shots for increasing and decreasing acoustic intensities, a hysteretic behaviour is experimentally observed on inertial cavitation activity, with a loop area sensitive to the inertial cavitation threshold. To get a better insight of the phenomena underlying this hysteretic effect, the evolution of the bubble size distribution is studied numerically by implementing rectified diffusion, fragmentation process, rising and dissolution of bubbles from an initial bubble size distribution.

Jumping acoustic bubbles on lipid bilayers.

In the context of sonoporation, we use supported lipid bilayers as a model for biological membranes and investigate the interactions between the bilayer and microbubbles induced by ultrasound. Among the various types of damage caused by bubbles on the surface, our experiments exhibit a singular dynamic interaction process where bubbles are jumping on the bilayer, forming a necklace pattern of alteration on the membrane. This phenomenon was explored with different time and space resolutions and, based on our observations, we propose a model for a microbubble subjected to the combined action of van der Waals, acoustic and hydrodynamic forces.

Sonoporation of adherent cells under regulated ultrasound cavitation conditions.

A sonoporation device dedicated to the adherent cell monolayer has been implemented with a regulation process allowing the real-time monitoring and control of inertial cavitation activity. Use of the cavitation-regulated device revealed first that adherent cell sonoporation efficiency is related to inertial cavitation activity, without inducing additional cell mortality. Reproducibility is enhanced for the highest sonoporation rates (up to 17%); sonoporation efficiency can reach 26% when advantage is taken of the standing wave acoustic configuration by applying a frequency sweep with ultrasound frequency tuned to the modal acoustic modes of the cavity.