Session R12: Biomedical, Cavitation and Acoustics II

Numerical study of ultrasonic bubble cavitation and viscoelastic solid deformation

Ultrasonic bubble cavitation, which induces considerable deformation of nearby solids by forming shock waves and high-speed liquid jets, has been applied to various engineering fields such as surface cleaning, medical therapy, and water purification. In this work, numerical study of ultrasound-driven bubble cavitation and solid deformation is performed by employing a full Eulerian method for effectively computing the fluid flow and solid deformation and a level-set method for tracking the bubble-water and water-solid interfaces. We use the Van der Waals equation for gas and Tait equation for liquid and solid to consider the compressibility effect of an ultrasonic pulse and shock wave, and a neo-Hookean model to include the elastic feature of solid. The present method for solid deformation is validated by comparing the numerical predictions of solid disk deformation in a lid-driven cavity with the results reported in the literature. Ultrasound-driven bubble motion and solid deformation patterns are analyzed according to the bubble-solid stand-off distance and the elastic shear modulus. The effect of the solid impedance on the shock wave pressure and liquid jet velocity inducing cavitation pits was further investigated by varying the bulk modulus and density of the solid.   

Numerical investigation of cavitation inside the brain and correlation with injury

Blast-induced traumatic brain injury is prevalent in people involved in military combat. Cavitation is being hypothesized as a possible mechanism of primary injury of brain cells following exposure to a blast wave. Experimental investigations of laser-generated cavitation bubbles in a brain tissue surrogate have shown that the growth and collapse of the bubbles generate enough stretching in the medium to induce cell damage, and injury thresholds have been obtained. In this study, we provide a correlation between the observed stretching thresholds for various brain cells and the characteristics of the pressure pulse that would induce such thresholds. The range of values of the pulse we choose is in accordance with experimental results on blast propagation inside a brain surrogate. The pulse is input into our single bubble cavitation model, which consists of a modified Keller-Miksis equation that takes the medium viscoelastic behavior into account. We studied cavitation activity for a wide range of initial nucleus sizes and found that the injury threshold is predominant around 2 microns, which is consistent with previous results. With this critical nucleus size, we explore the space of the pulse parameters and relate cavitation to injury. These correlations will help determine safety limits against blast-induced traumatic injury.   

Numerical simulation of microbubble-assisted ultrasound therapy for thermal ablation

A fully compressible multiscale model for the simulation of microbubble assisted High-Intensity Focused Ultrasound (HIFU) is presented. HIFU is a non-invasive therapy where high-intensity ultrasound waves are focused onto a target tissue to cause thermal ablation as a result of localized energy deposition. The non-linear ultrasonic field is modeled using compressible Navier-Stokes equations on a fixed grid, while the microbubbles are tracked as discrete singularities in a Lagrangian fashion. These two models are coupled to each other such that both the acoustic field and the bubbles influence each other. The energy absorbed by the medium locally due to the focused ultrasound and bubble dynamics is then used to compute the temperature rise in the focal and surrounding regions by solving a bio-heat transfer equation over the entire insonation time period. We first demonstrate the HIFU simulation without microbubbles and characterize the pressure and temperature fields by validating against available experiments. Experimental validation in the presence of microbubbles is then carried out to demonstrate the accuracy of the model. We then study the effect of microbubbles in the focal region on altering the energy absorption by the tissue.   

Ultrasound-induced dynamics of microbubbles near a boundary: vibrations, shape modes and jets.

Despite the demonstrated clinical utility of microbubbles in targeted drug delivery using ultrasound, the fundamental mechanism driving this process is still not fully understood. The occurrence of microdamage on soft biomaterials at the low acoustic intensities used in clinical practice cannot be attributed to inertial cavitation. Our objective is to address this knowledge gap by exploring the rich dynamics of acoustically driven single bubbles near a boundary and the role of their shape modes in inducing microjets. We leverage simultaneous high-speed phase-contrast X-ray and visible light shadowgraphy imaging to capture both the side and top views of single gas microbubbles that rest against a flat substrate and are driven by an ultrasound pulse. Through this, we are able to reconstruct the time-dependent morphology of the bubble revealing a specific sequence of events, starting with volumetric oscillation, followed by the inception of harmonic axisymmetric shape-modes, transitioning to half-harmonic ones, and finally, experiencing symmetry breakage and developing non-zonal shape modes. Notably, we discover that when the interfacial acceleration exceeds a certain threshold, the valleys of the shape deformation transition into jets directed toward the substrate at every cycle.   

Numerical investigation on cavitation induced tissue injury during ultrasound treatments.

Cavitation in medical applications is increasingly used for kidney stone fracture in shock wave lithotripsy (SWL), drag and gene delivery through encapsulated bubbles, blood brain barrier (BBB) permeability and in high intensity focused ultrasound (HIFU) among others. Despite the beneficial use of cavitation in these procedures, the exact mechanism of the adverse effects that are being reported, such as hemorrhage, still is not fully understood. In this work we present numerical simulations of cavitation induced soft tissue interaction/injury during ultrasound and shock wave treatments, to elucidate the bubble interaction with soft tissue and rigid bio materials such as kindey stones. To this end a novel numerical solver was developed (ForestFV), that employs a Diffuse Interface Method (DIM) able to capture multi-phase, fluid-solid interactions (FSI), complex shock wave interactions and bubble dynamics, in various spatial and temporal scales using an adaptive mesh refinement (AMR) framework for unstructured grids. The presented numerical framework has been validated against other numerical and experimental test cases. Three different configurations will be presented. In the first cases, a novel tension driven tissue injury mechanism is highlighted for the inertial collapse of attached and detached bubbles on soft tissue. In the next configuration, we demonstrate that the resulting liquid jet from a collapsing bubble can penetrate a blood vessel wall and cause hemorrhage, a typical side effect during high intensity ultrasound. Finally, in the last cases, we present large scale oscillations of bubbles within a capillary the stress development inside the soft tissue wall, as well as the injury potential of stable cavitation to various blood vessels.   

Shockwave-induced droplet vaporization

Phase-transition of nanometer and micrometer sized droplets to gaseous bubbles using ultrasound (termed acoustic droplet vaporization or ADV) has been studied for a range of biomedical applications, such as targeted drug delivery, transient opening of the blood-brain-barrier, and embolotherapy. Yet, the underlying physics governing ADV is not well understood. It is widely assumed that nucleation in the droplet bulk is caused mainly by the low-pressure portion of the incoming acoustic wave transmitted through the droplet itself. However, recent studies have shown the possibility of phase reversal of spherically converging acoustic waves, which suggest that the compressive part of the acoustic wave may contribute to the droplet vaporization as well. Here, we demonstrate this by performing high-speed videomicroscopy of micrometric droplet vaporization triggered by laser-induced shockwaves, which presents a strong pressure peak and reduced tensile region. These experimental observations, further supported with theoretical modeling, highlight the importance of the compressive field on ultrasound-induced ADV.   

Mixing enhancement of viscous droplet using an oscillating bubble on a digital microfluidic device

In this paper, we present a novel digital microfluidic (DMF) device that utilizes an acoustically excited bubble for droplet mixing. The proposed DMF device not only manipulate droplets but also generate microstreaming inside the droplet, by using electrowetting (EW) and bubble oscillation, respectively. We use the microstreaming which is generated by a bubble oscillating by a piezoactuator. The design of the proposed DMF device with holes for bubble generation on each EW electrode were devised. When a droplet is initially placed on an EW electrode with a hole, the bubble is trapped inside the hole. Then, when the piezoactuator is activated, the microstreaming is induced by the acoustically oscillating bubble. To analyze this microstreaming, visualization experiment and velocity measurement were conducted. Furthermore, we investigated the performance of droplet mixing by quantifying mixing index of liquid droplets through image processing. The proposed device would be useful to handle micro-droplets with various properties in medical and biological fields.   

Magnetically maneuverable microrobot using acoustic bubbles for targeted drug delivery technology.

This paper proposes a new type of magnetically maneuverable microrobot using acoustic bubbles aimed at multiphase drug delivery to target tissues inside human blood vessels. The proposed microrobot utilizes two bubbles embedded in a microtube to contain solid and liquid drugs and uses magnetic actuation to transport the drugs to the target tissue. And when an acoustic wave was applied to the bubbles, the drugs can be released into the target tissues by microstreaming generated from acoustically oscillated bubbles. The proposed microrobot consists of the microtube with bubbles and a liquid metal, which was fabricated using microfabrication technology based on an ultra-precise 3D printer. We conducted experiments to transport the microrobot to a specified location using a permanent magnet. Using a high-speed camera, we carried out the conditions for releasing the drug according to the length of the bubbles, the frequencies of the acoustic wave, and the viscosities of the drugs. As proof of concept, the proposed microrobot is demonstrated by transporting and releasing liquid and solid drugs to target locations in microchannels that mimic blood vessels. Although the proposed microrobot has a simple structure, it is expected to improve the efficiency of targeted drug delivery due to transporting drugs to the target tissues and manipulating multiphase drugs.