Session M21: Bubbles: Biomedical Acoustics and Cavitation

Growth and collapse of an acoustically generated cavitation bubble

Acoustic cavitation has been used for a variety of applications including therapeutic ultrasound procedures (e.g., lithotripsy, histotripsy), ultrasonic cleaning. When a gas nucleus is exposed to strong transient rarefaction waves, it undergoes an explosive growth and violent collapse, leading to the generation of shock waves and large deformation of surrounding materials, which may damage the nearby rigid surface or biological tissue. However, the relation between input parameters (e.g., external waveform, nucleus size) and outputs (e.g., maximum bubble radius and energy concentration at collapse), which is relevant to predict damage, is not fully determined to the larger parameter space and complex physics involved in the bubble oscillation. In this study, we develop a framework for energy transfer in the system to distinguish the major effects determining the bubble dynamics. Using this framework, we obtain the scaling relations to describe the bubble stretch during the growth and energy concentration at collapse using the external waveforms and nucleus size. These relations for a gas bubble in liquid may help us to estimate the damage potential and develop better strategies to control cavitation bubbles and provide a baseline to further investigate the cavitation-induced damage in tissue.   

Cavitation bubbles in tissue simulants

Cavitation formation and dynamics in the human body, when subjected to rapid mechanical load, is being considered as a possible injury mechanism. We consider cavitation in a tissue simulant utilizing four different gel types: gelatin A/B, agar, and agarose. The gels are prepared at different gel concentrations (c) in pure water for each gel type so that the effect of gel’s properties on cavitation can be experimentally characterized. A well-controlled mechanical impact is applied to each sample to simulate typical brain injury scenarios. For gelatin A/B, the critical acceleration (a_cr) that triggers the onset of inertial cavitation monotonically rises with increasing gel stiffness and spherical bubbles are observed regardless of c. In contrast, the a_cr for agar and agarose monotonically increases, but followed by plateau. In addition, bubble shape transitions from sphere to saucer with increasing c. We hypothesize that hydrophobic molecular bundles in agar and agarose cause these unique responses. Our theoretical analysis using both Rayleigh-Plesset and fracture-based models confirms that our proposed mechanisms offer reasonable explanations for the observed cavitation behavior in soft tissue simulants.   

Jets from interacting cavitation bubbles

Ultrafast microjet generation has sparked interest due to its potential application in needle-free injections to enable mass vaccination. Cavitation bubbles collapsing near surfaces can produce high-speed jets, but their direction is difficult to control near biological interfaces due to their elasticity. Introducing cavitation bubble pairs to generate jets, however, can overcome this difficulty. Here we show, experimentally and numerically, that a variety of dimensionless parameters such as the bubble size ratio, the distance between the bubbles, and the time difference in the bubble generation govern the dynamics of a pair of interacting cavitation bubbles and the resulting jets. These parameters can manoeuvre the jets' direction and velocity, reaching values of up to hundreds of metres per second. The mechanism behind ultrafast jets is also revealed, suggesting that a rebounding bubble imparts momentum to the liquid contained between bubbles and focuses the flow onto the neighbouring bubble, resulting in powerful jets. Finally, we also demonstrate that these jets can penetrate soft materials. The results highlight their potential in controlled, precise, and directional use in therapeutic (e.g., cell perforation, cell transfection) and needle-free drug-delivery applications.   

Dynamics of confined cavitation bubbles, a possible link with mild traumatic brain injuries.

Traumatic Brain Injury (TBI) is a major healthcare problem, increasingly occurring in sports like rugby, boxing or football. The occurrence of TBI is dependent on the head acceleration and the duration of the shock, as expressed by the empirical Wayne State Tolerance Curve (WSTC). One of the possible causes of TBI is the formation of cavitation bubbles in the cerebro-spinal fluid (CSF). To investigate the link between TBI and cavitation bubbles, we built a model experiment to induce cavitation bubbles through an impact. A tank is entirely filled with water (representing the CSF) and hermetically closed with a flexible membrane (mimicking the CSF circulation between the head and the spinal cord). The tank is impacted on a damper, and the formation and dynamics of cavitation bubbles is observed and studied. After showing that the damaging capacities of such bubbles are in good agreement with the WSTC, we seeked to study the influence of the brain: the CSF does not fill the whole cranial cavity, but is confined between the skull and the brain on a thickness of approximately 1mm. We introduced a confined area in the head-like water tank that allows us to compare the dynamics of confined and unconfined bubbles for the same shock. Modeling those confined cavitation bubbles induced by a shock allows us to compute their damaging capacities and conclude on the dangerousness of shocks received by athletes.   

Vapor and gas bubble growth with phase transition near a wall

Bubbles cavitate near hard surfaces during biomedical therapies, such as ultrasound-focused breakup of urinary stones. The bubbles oscillate during the treatment due to the compressive and tensile ultrasound pressures. During the oscillations, the liquid evaporates into the gas bubble, water vapor condenses, and non-condensable gases dissolve into the liquid. These dynamics have been studied in 1D spherical symmetric numerical simulations. We conduct simulations of asymmetric bubble dynamics near a rigid wall with three phases (liquid, vapor, and gas) using the open-source Multi-component Flow Code [Bryngelson et al. Comp. Phys. Comm. (2020)]. MFC solves the 3D, compressible Navier-Stokes equations using a six-equation multiphase numerical model including phase change. We verify the solver using 1D shock tube and 2D underwater explosion simulations. We observe condensation at the bubble interface during ultrasound-induced vapor-gas oscillations. Results varying driving pressure, frequency, and bubble stand-off distances will also be presented.   

Microbubble collapse near a viscoelastic solid boundary

Bubble jets are fast liquid jets caused by the asymmetric collapse of gas bubbles. Even a microscale bubble can generate a jet with the speed of a few hundred meters per second, exerting a large impulse onto a nearby structure. Many studies have revealed that the bubble jet dynamics change significantly by the physical properties of nearby boundaries. However, a bubble jet behavior near a viscoelastic boundary remains unknown despite its importance in industrial and biomedical applications. This study numerically investigates the interaction of a bubble jet near a viscoelastic solid, modeled by the Kelvin-Voigt material, using a coupled algorithm of finite volume method and finite element method. The bubble jet dynamics change significantly by variations in viscoelastic properties, which can be explained by scaling analyses of the interaction between the bubble jet and the viscoelastic solid. It has been found that the relative characteristic time scale of the viscoelastic solid primarily affects the change in the overall bubble jet dynamics.   

Cavitation effects in ultrasound-enhanced soft tissue adhesion

Hydrogel-tissue adhesives have a number of applications including wound dressing and regenerative medicine. It has been recently shown that submitting a soft tissue covered with a viscous binding matrix to ultrasound treatment before patching it with hydrogel enhances the adhesion significantly. The exact mechanism responsible for this effect is unclear, but it is believed to be cavitation. The present study aims at confirming this hypothesis by numerically and experimentally exploring the influence of the various aspects of the ultrasound treatment: acoustic pressure field, cavitation inception on the surface, viscous absorption and shear-thinning behavior of the binding matrix. The pressure field around the ultrasonic horn is determined numerically for varying excitation amplitude and distance between the ultrasonic horn and the tissue. This allows for an approximation of the cavitation aggressiveness and of the surface area of the tissue affected, which can be compared with the experimentally observed spatial control of the adhesion.   

Time-resolved response of microbubble ultrasound contrast agents driven by traveling acoustic waves

Microbubble ultrasound contrast agents have been used for more than two decades in medical sonography to enhance the contrast between the blood pool and the surrounding tissue. Recently, such agents have been promoted as drug carriers for targeted drug administration mediated by ultrasound. Despite the progress achieved, a full understanding of the microbubble behavior that stimulates drug uptake is still lacking which hinders their translation to clinical practice. Our experimental studies are aimed at a detailed characterization of the translational, non-linear oscillation and clustering dynamics of ultrasound contrast agents. The microbubble dynamics, driven by MHz-frequency ultrasound, is recorded over a range of diameters and pressures through ultra-high-speed videomicroscopy imaging. Time-resolved experiments reveal the response of individual microbubbles and the distinct dynamical features of their interfaces. The results are compared with theoretical predictions and serve to gain further insights on the role of the encapsulating shell in the overall microbubble dynamics.   

Modelling lipid-coated microbubbles at subresonance frequencies

We present a computational study of a lipid-coated SonoVue microbubble, excited at subresonance frequencies (200-1500 kHz) and pressure amplitudes (100-1500 kPa) frequently considered for focused ultrasound applications. The bubble dynamics are modelled with the Rayleigh-Plesset equation and the Gilmore equation, together with the Marmottant model for the lipid monolayer coating. Below the onset of inertial cavitation, a linear regime bounded by the Blake pressure is identified in which the maximum pressure at the bubble wall is linearly proportional to the mechanical index. In the nonlinear regime the maximum pressure at the bubble wall is readily predicted by the maximum bubble radius, and both the Rayleigh-Plesset and Gilmore equations predict the onset of sub- and ultraharmonic frequencies of the acoustic emissions compared to in vitro experiments. Accounting for the lipid coating turns out to be critical for the accurate prediction of the bubble behaviour.   

Development of microbubble-encapsulated-vesicles generation method using flow-focusing device

The method of generating the Microbubble-enCapsulated-Vesicles (MCV) using flow-focusing device is discussed. First, monodisperse micro-droplets containing microbubbles are generated using flow-focusing device. Then, the vesicles are prepared by adsorbing phospholipids to surface of the droplets with the inverted emulsion method.

Droplet formation process can be classified into three regimes by the capillary number divided by the orifice width. At a low capillary number, the dispersed phase blocks the orifice and breaks into droplets. Therefore, the equivalent hydraulic diameter of the orifice and flow rate of the continuous phase has a great influence on the droplet size. At a high capillary number, the dispersed phase are stretched by the shear force and split into small droplets. The viscosity and flow rate of the continuous phase are the important factors in droplet formation. Furthermore, the influence of containing microbubbles will be also discussed in the presentation.