Inertial Cavitation Threshold Research Articles

Enhancing sonothrombolysis outcomes with dual-frequency ultrasound: Insights from an in silico microbubble dynamics study

Sonothrombolysis is a technique that employs the ultrasound waves to break down the clot. Recent studies have demonstrated significant improvement in the treatment efficacy when combining two ultrasound waves of different frequencies. Nevertheless, the findings remain conflicted on the ideal frequency pairing that leads to an optimal treatment outcome. Existing experimental studies are constrained by the limited range of frequencies that can be investigated, while numerical studies are typically confined to spherical microbubble dynamics, thereby restricting the scope of the analysis. To overcome this, the present study investigated the microbubble dynamics caused by the different combinations of ultrasound frequencies. This was carried out using computational modelling as it enables the visualisation of the microbubble behaviour, which is difficult in experimental studies due to the opacity of blood. The results showed that the pairings of two ultrasound waves with low frequencies generally produced stronger cavitation and higher flow-induced shear stress on the clot surface. However, one should avoid the frequency pairings that are integer multipliers of each other, i.e., frequency ratio of 1/3, 1/2 and 2, as they led to resultant wave with low pressure amplitude that weakened the cavitation. At 0.5 + 0.85 MHz, the microbubble caused the highest shear stress of 60.5 kPa, due to its large translational distance towards the clot. Although the pressure threshold for inertial cavitation was reduced using dual-frequency ultrasound, the impact of the high-speed jet can only be realised when the microbubble travelled close to the clot. The results obtained from the present study provide groundwork for deeper understanding on the microbubble dynamics during dual-frequency sonothrombolysis, which is of paramount importance for its optimisations and the subsequent clinical translation.

Cavitation-induced pressure saturation: a mechanism governing bubble nucleation density in histotripsy

Objective. Histotripsy is a noninvasive focused ultrasound therapy that mechanically disintegrates tissue by acoustic cavitation clouds. In this study, we investigate a mechanism limiting the density of bubbles that can nucleate during a histotripsy pulse. In this mechanism, the pressure generated by the initial bubble expansion effectively negates the incident pressure in the vicinity of the bubble. From this effect, the immediately adjacent tissue is prevented from experiencing the transient tension to nucleate bubbles. Approach. A Keller–Miksis-type single-bubble model was employed to evaluate the dependency of this effect on ultrasound pressure amplitude and frequency, viscoelastic medium properties, bubble nucleus size, and transducer geometric focusing. This model was further combined with a spatial propagation model to predict the peak negative pressure field as a function of position from a cavitating bubble. Main results. The single-bubble model showed the peak negative pressure near the bubble surface is limited to the inertial cavitation threshold. The predicted bubble density increased with increasing frequency, tissue viscosity, and transducer focusing angle. The simulated results were consistent with the trends observed experimentally in prior studies, including changes in density with ultrasound frequency and transducer F-number. Significance. The efficacy of the therapy is dependent on several factors, including the density of bubbles nucleated within the cavitation cloud formed at the focus. These results provide insight into controlling the density of nucleated bubbles during histotripsy and the therapeutic efficacy.

A model of coupled oscillation of bubble cluster in liquid cavity wrapped by viscoelastic medium

Considering the interactions between bubbles in a multi-bubble system in a liquid micro-cavity, a spherical bubble cluster in a liquid cavity is modeled in order to describe the dynamical effect of the viscoelastic medium outside the liquid cavity on the oscillation of bubbles, and the coupled equations of bubbles are obtained. Subsequently, the acoustic response characteristics of bubbles are investigated by analyzing the radial oscillation, the stability of the non-spherical shape of bubbles and the threshold of inertial cavitation. The results show that the confinement of the cavity and the bubble cluster facilitates the suppression of bubble oscillation, however, it might enhance the nonlinear properties of bubbles to a certain extent. From the acoustic response curve at 1 MHz, it is found that the main resonance peaks shift leftward with the increase of the bubble number, which means a minor resonant radius can be obtained. The nonlinear stability of bubbles in a confined environment is mainly determined by acoustic pressure amplitude and frequency, the initial bubble radius, and bubble number density, while the effect of the cavity radius is enhanced with the increase of the driving pressure. There is a minimum unstable driving acoustic pressure threshold, depending on the initial bubble radius, and the unstable regions are mainly located in a range of less than 4 μm. With the increase in bubble number density, the strip-type stable region scattered of the unstable region in the map is gradually transformed into a random patch-like distribution, which indicates that the bubble oscillation under high acoustic pressure is more sensitive to the parameters, and it is very susceptible to interference, produces unstable oscillation and then collapses. When the bubble equilibrium radius is in a range greater than 4 μm, the influences of frequency and bubble number density on the inertial thresholds are particularly significant.

Improved assessment sensitivity of time-varying cavitation events based on wavelet analysis

Ultrasonic cavitation, characterized by the oscillation or abrupt collapse of cavitation nuclei in response to ultrasound stimulation, plays a significant role in various applications within both industrial and biomedical sectors. In particular, inertial cavitation (IC) has garnered considerable attention due to the resulting mechanical, chemical, and thermal effects. Passive cavitation detection (PCD) has emerged as a valuable technique for monitoring this procedure. While the fast Fourier transform (FFT) is a widely used algorithm to analyze IC-induced broadband noise detected by PCD system, it may not adequately capture the time-varying instability of cavitation due to potential nuclei collapse during ultrasound irradiation. In contrast, the continuous wavelet transform offers a more flexible approach, enabling more sensitive analysis of signals with varying frequencies over time. In this study, nanodiamond (ND) and its derivative, nitro-doped nanodiamond (N-AND), known to possess cavitation potential from previous research, were chosen as the source of cavitation nuclei. The cavitation signals detected by PCD were subjected to both FFT and wavelet analyses, with their results comprehensively compared. This research showcased the feasibility of employing wavelet analysis for effective inertial cavitation evaluation. It provided the advantage of monitoring the temporal evolution of cavitation events in real-time, enhancing sensitivity to weak and unstable cavitation signals, especially those in higher order components (3rd and 4th order). Additionally, it yielded a higher level of precision in determining IC thresholds and doses. Furthermore, the inclusion of time information through wavelet analysis offered insights into the limitations of low-cycle ultrasound in inducing IC. This study introduces a novel perspective for more sensitive and precise cavitation assessment, leveraging time and frequency data from wavelet analysis, and holds promise for effective utilization of cavitation effects while minimizing losses and damages resulting from unintended cavitation events.

Investigation of the effect of a multi-frequency ultrasound signal on the inertial cavitation threshold is various viscoelastic mediums

The objective of the present study is the numerical investigation of the inertial cavitation threshold in soft tissue under different multi-frequency signals of high intensity focused ultrasound (HIFU). For the modeling of bubble dynamics, the Gilmore-Akulichev-Zener model was used. The inertial cavitation threshold was calculated for different criteria, for different signal modes (single-, dual-, and triple-frequency), and for different viscoelastic mediums. Effect of nonlinear wave propagation and mechanical effects of acoustic caviation have been also studied. The obtaining results demonstrated that a criterion, based on bubble size, gives lower threshold values than a criterion using bubble collapse velocity. An increase in the values of viscosity and elasticity leads to a rise in the threshold amplitude. Analyzing threshold values for dual- and triple-frequency signal modes, it can be seen that the inertial cavitation threshold can be sufficiently reduced when a multi-frequency signal with the correct frequency combination is applied. However, the inertial cavitation threshold also depends on the initial bubble size. This dependency was also investigated in the current study.

Effect of temperature on the acoustic response and stability of size-isolated protein-shelled ultrasound contrast agents and SonoVue.

Limited work has been reported on the acoustic and physical characterization of protein-shelled UCAs. This study characterized bovine serum albumin (BSA)-shelled microbubbles filled with perfluorobutane gas, along with SonoVue, a clinically approved contrast agent. Broadband attenuation spectroscopy was performed at room (23 ± 0.5 °C) and physiological (37 ± 0.5 °C) temperatures over the period of 20 min for these agents. Three size distributions of BSA-shelled microbubbles, with mean sizes of 1.86 μm (BSA1), 3.54 μm (BSA2), and 4.24 μm (BSA3) used. Viscous and elastic coefficients for the microbubble shell were assessed by fitting de Jong model to the measured attenuation spectra. Stable cavitation thresholds (SCT) and inertial cavitation thresholds (ICT) were assessed at room and physiological temperatures. At 37 °C, a shift in resonance frequency was observed, and the attenuation coefficient was increased relative to the measurement at room temperature. At physiological temperature, SCT and ICT were lower than the room temperature measurement. The ICT was observed to be higher than SCT at both temperatures. These results enhance our understanding of temperature-dependent properties of protein-shelled UCAs. These findings study may guide the rational design of protein-shelled microbubbles and help choose suitable acoustic parameters for applications in imaging and therapy.

An optical and acoustic investigation of microbubble cavitation in small channels under therapeutic ultrasound conditions.

Therapeutic focused ultrasound in combination with encapsulated microbubbles is being widely investigated for its ability to elicit bioeffects in the microvasculature, such as transient permeabilization for drug delivery or at higher pressures to achieve 'antivascular' effects. While it is well established that the behaviors of microbubbles are altered when they are situated within sufficiently small vessels, there is a paucity of data examining how the bubble population dynamics and emissions change as a function of channel (vessel) diameter over a size range relevant to therapeutic ultrasound, particularly at pressures relevant to antivascular ultrasound. Here we use acoustic emissions detection and high-speed microscopy (10 kframes/s) to examine the behavior of a polydisperse clinically employed agent (Definity®) in wall-less channels as their diameters are scaled from 1200 to 15µm. Pressures are varied from 0.1 to 3MPa using either a 5ms pulse or a sequence of 0.1ms pulses spaced at 1ms, both of which have been previously employed in an in vivo context. With increasing pressure, the 1200µm channel - on the order of small arteries and veins - exhibited inertial cavitation, 1/2 subharmonics and 3/2 ultraharmonics, consistent with numerous previous reports. The 200 and 100µm channels - in the size range of larger microvessels less affected by therapeutic focused ultrasound - exhibited a distinctly different behavior, having muted development of 1/2 subharmonics and 3/2 ultraharmonics and reduced persistence. These were associated with radiation forces displacing bubbles to the distal wall and inducing clusters that then rapidly dissipated along with emissions. As the diameter transitioned to 50 and then 15µm - a size regime that is most relevant to therapeutic focused ultrasound - there was a higher threshold for the onset of inertial cavitation as well as subharmonics and ultraharmonics, which importantly had more complex orders that are not normally reported. Clusters also occurred in these channels (e.g. at 3MPa, the mean lateral and axial sizes were 23 and 72µm in the 15µm channel; 50 and 90µm in the 50µm channel), however in this case they occupied the entire lumens and displaced the wall boundaries. Damage to the 15µm channel was observed for both pulse types, but at a lower pressure for the long pulse. Experiments conducted with a 'nanobubble' (<0.45µm) subpopulation of Definity followed broadly similar features to 'native' Definity, albeit at a higher pressure threshold for inertial cavitation. These results provide new insights into the behavior of microbubbles in small vessels at higher pressures and have implications for therapeutic focused ultrasound cavitation monitoring and control.

Acoustic Detection of Retained Perfluoropropane Droplets Within the Developing Myocardial Infarct Zone.

Perfluoropropane droplets (PDs) cross endothelial barriers and can be acoustically activated for selective myocardial extravascular enhancement following intravenous injection (IVI). Our objective was to determine how to optimally activate extravascular PDs for transthoracic ultrasound-enhanced delineation of a developing scar zone (DSZ). Ultrafast-frame-rate microscopy was conducted to determine the effect of pulse sequence on the threshold of bubble formation from PDs. In vitro studies were subsequently performed at different flow rates to determine acoustic activation and inertial cavitation thresholds for a PD infusion using multipulse fundamental non-linear or single-pulse harmonic imaging. IVIs of PDs were given in 9 rats and 10 pigs following prolonged left anterior descending ischemia to detect and quantify PD kinetics within the DSZ. A multipulse sequence had a lower myocardial index threshold for acoustic activation by ultrafast-frame-rate microscopy. Acoustic activation was observed at a myocardial index ≥0.4 below the inertial cavitation threshold for both pulse sequences. In rats, confocal microscopy and serial acoustic activation imaging detected higher droplet presence (relative to remote regions) within the DSZ at 3 min post-IVI. Transthoracic high-mechanical-index impulses with fundamental non-linear imaging in pigs at this time post-IVI resulted in selective contrast enhancement within the DSZ.

Acoustic droplet vaporization for nonthermal ablation of brain tumors

Acoustic vaporization of perfluorobutane-based phase-shift nanoemulsions (PSNE) can be used to nucleate inertial cavitation (IC) in vivo. The acoustic pressure amplitude must exceed a threshold for vaporization of PFB-based nanoemulsions. Two focused ultrasound transducers with a center frequency of 837 kHz were oriented such that their focal volumes overlapped and the acoustic pressure amplitude was amplified. In this study, the dual transducer system was combined with circulating PSNE to nucleate IC in established brain tumors, leading to nonthermal ablation of the tumors. For comparison, microbubble ultrasound agents (UCA) were used as IC nuclei for ultrasound-mediated tumor ablation. The ablation volume was confined to focal volume when PSNE were used to nucleate IC, whereas pre-focal damage was observed when UCA were used as IC nuclei. Additionally, PSNE-nucleated IC ablated a larger percentage of the brain tumors on average than MB-nucleated IC (89.46.8% vs 11.17.7%, respectively). These results suggest that PFB-based PSNE may be used to significantly reduce the inertial cavitation threshold in the cerebrovasculature, and when combined with transcranial focused ultrasound, enable efficient focal intracranial nonthermal ablation.

GPU-accelerated study of the inertial cavitation threshold in viscoelastic soft tissue using a dual-frequency driving signal

Inertial cavitation thresholds under two forms of ultrasonic excitation (the single- and dual-frequency ultrasound modes) are studied numerically. The Gilmore–Akulichev model coupled with the Zener viscoelastic model is used to model the bubble dynamics. The threshold pressures are determined with two criteria, one based on the bubble radius and the other on the bubble collapse speed. The threshold behavior is investigated for different initial bubble sizes, acoustic signal modes, frequencies, tissue viscosities, tissue elasticities, and all their combinations. Due to the large number of parameters and their many combinations (around 1.5 billion for each threshold criterion), all simulations were executed on graphics processing units to speed up the calculations. We used our own code written in the C++ and CUDA C languages. The results obtained demonstrate that using the dual-frequency signal mode can help to reduce the inertial cavitation threshold (in comparison to the single-frequency mode). The criterion based on the bubble size gives a lower threshold than the criterion using the bubble collapse speed. With an increase of the elasticity, the threshold pressure also increases, whereas changing the viscosity has a very small impact on the optimal threshold, unlike the elasticity. A detailed analysis of the optimal ultrasound frequencies for a dual-frequency driving signal found that for viscosities less than 0.02 Pa·s, the first optimal frequency, in general, is much smaller than the second optimal frequency, which can reach 1 MHz. However, for high viscosities, both optimal frequencies are similar and varied in the range 0.01–0.05 MHz. Overall, this study presents a detailed analysis of inertial cavitation in soft tissue under dual-frequency signal excitation. It may be helpful for the further development of different applications of biomedical ultrasound.

Gpu-Accelerated Study of the Inertial Cavitation Threshold in Viscoelastic Soft Tissue Using a Dual-Frequency Driving Signal

Gpu-Accelerated Study of the Inertial Cavitation Threshold in Viscoelastic Soft Tissue Using a Dual-Frequency Driving Signal

GPU-Accelerated Study of the Inertial Cavitation Threshold in Viscoelastic Soft Tissue Using a Dual-Frequency Driving Signal

GPU-Accelerated Study of the Inertial Cavitation Threshold in Viscoelastic Soft Tissue Using a Dual-Frequency Driving Signal

Cavitation Dynamics and Inertial Cavitation Threshold of Lipid Coated Microbubbles in Viscoelastic Media with Bubble-Bubble Interactions.

Encapsulated microbubbles combined with ultrasound have been widely utilized in various biomedical applications; however, the bubble dynamics in viscoelastic medium have not been completely understood. It involves complex interactions of coated microbubbles with ultrasound, nearby microbubbles and surrounding medium. Here, a comprehensive model capable of simulating the complex bubble dynamics was developed via taking the nonlinear viscoelastic behaviors of the shells, the bubble–bubble interactions and the viscoelasticity of the surrounding medium into account simultaneously. For two interacting lipid-coated bubbles with different initial radii in viscoelastic media, it exemplified that the encapsulating shell, the inter-bubble interactions and the medium viscoelasticity would noticeably suppress bubble oscillations. The inter-bubble interactions exerted a much stronger suppressing effect on the small bubble within the parameters examined in this paper, which might result from a larger radiated pressure acting on the small bubble due to the inter-bubble interactions. The lipid shells make the microbubbles exhibit two typical asymmetric dynamic behaviors (i.e., compression or expansion dominated oscillations), which are determined by the initial surface tension of the bubbles. Accordingly, the inertial cavitation threshold decreases as the initial surface tension increases, but increases as the shell elasticity and viscosity increases. Moreover, with the distance between bubbles decreasing and/or the initial radius of the large bubble increasing, the oscillations of the small bubble decrease and the inertial cavitation threshold increases gradually due to the stronger suppression effects caused by the enhanced bubble–bubble interactions. Additionally, increasing the elasticity and/or viscosity of the surrounding medium would also dampen bubble oscillations and result in a significant increase in the inertial cavitation threshold. This study may contribute to both encapsulated microbubble-associated ultrasound diagnostic and emerging therapeutic applications.

Acoustic Droplet Vaporization of Perfluorocarbon Droplets in 3D-Printable Gelatin Methacrylate Scaffolds

Scientists face a significant challenge in creating effective biomimetic constructs in tissue engineering with sustained and controlled delivery of growth factors. Recently, the addition of phase-shift droplets inside the scaffolds is being explored for temporal and spatial control of biologic delivery through vaporization using external ultrasound stimulation. Here, we explore acoustic droplet vaporization (ADV) in gelatin methacrylate (GelMA), a popular hydrogel used for tissue engineering applications because of its biocompatibility, tunable mechanical properties and rapid reproducibility. We embedded phase-shift perfluorocarbon droplets within the GelMA resin before crosslinking and characterized ADV and inertial cavitation (IC) thresholds of the embedded droplets. We were successful in vaporizing two different perfluorocarbon---perfluoropentane (PFP) and perfluorohexane (PFH)--cores at 2.25- and 5-MHz frequencies and inside hydrogels with varying mechanical properties. The ADV and IC thresholds for PFP droplets in GelMA scaffolds increased with frequency and in stiffer scaffolds. The PFH droplets exhibited ADV and IC activity only at 5 MHz for the range of excitations below 3MPa investigated here and at threshold values higher than those of PFP droplets. The results provide a proof of concept for the possible use of ADV in hydrogel scaffolds for tissue engineering.

Investigation of the Acoustic Vaporization Threshold of Lipid-Coated Perfluorobutane Nanodroplets Using Both High-Speed Optical Imaging and Acoustic Methods

A combination of ultrahigh-speed optical imaging (5 × 106 frames/s), B-mode ultrasound and passive cavitation detection was used to study the vaporization process and determine both the acoustic droplet vaporization (ADV) and inertial cavitation (IC) thresholds of phospholipid-coated perfluorobutane nanodroplets (PFB NDs, diameter = 237 ± 16 nm). PFB NDs have not previously been studied with ultrahigh-speed imaging and were observed to form individual microbubbles (1–10 μm) within two to three cycles and subsequently larger bubble clusters (10–50 μm). The ADV and IC thresholds did not statistically significantly differ and decreased with increasing pulse length (20–20,000 cycles), pulse repetition frequency (1–100 Hz), concentration (108–1010 NDs/mL), temperature (20°C–45°C) and decreasing frequency (1.5–0.5 MHz). Overall, the results indicate that at frequencies of 0.5, 1.0 and 1.5 MHz, PFB NDs can be vaporized at moderate peak negative pressures (<2.0 MPa), pulse lengths and pulse repetition frequencies. This finding is encouraging for the use of PFB NDs as cavitation agents, as these conditions are comparable to those required to achieve therapeutic effects with microbubbles, unlike those reported for higher-boiling-point NDs. The differences between the optically and acoustically determined ADV thresholds, however, suggest that application-specific thresholds should be defined according to the biological/therapeutic effect of interest.

Cavitation Therapy Monitoring of Commercial Microbubbles With a Clinical Scanner.

The ability to monitor cavitation activity during ultrasound and microbubble-mediated procedures is of high clinical value. However, there has been little reported literature comparing the cavitation characteristics of different clinical microbubbles, nor have current clinical scanners been used to perform passive cavitation detection in real time. The goal of this work was to investigate and characterize standard microbubble formulations (Optison, Sonovue, Sonazoid, and a custom microbubble made with similar components as Definity) with a custom passive cavitation detector (two confocal single-element focused transducers) and with a Philips EPIQ scanner with a C5-1 curvilinear probe passively listening. We evaluated three different methods for investigating cavitation thresholds, two from previously reported work and one developed in this work. For all three techniques, it was observed that the inertial cavitation thresholds were between 0.1 and 0.3 MPa for all agents when detected with both systems. Notably, we found that most microbubble formulations in bulk solution behaved generally similarly, with some differences. We show that these characteristics and thresholds are maintained when using a diagnostic ultrasound system for detecting cavitation activity. We believe that a systematic evaluation of the frequency response of the cavitation activity of different microbubbles in order to inform real-time therapy monitoring using a clinical ultrasound device could make an immediate clinical impact.

Dynamic analysis of bubble in liquid cavity wrapped by viscoelastic medium

Ultrasonic wave with higher intensity will directly cavitate in soft tissue. It is an important issue in ultrasonic therapy that the cavitation bubbles in soft tissues are driven in the ultrasonic field. It is assumed that the medium inside the bubble is gas, the cavity is filled with the incompressible viscous liquid, and the medium surrounding the cavity is viscoelastic solid. To introduce the effect of the surrounding tissue, it is assumed that the tissue is incompressible, linear and Voigt viscoelastic solid. The motion of a cavitation bubble can be affected by many factors, such as acoustic pressure, acoustic frequency, tissue elasticity and cavity size. Numerical simulation shows that the resonance frequency and amplitude of the bubbles decrease with cavity radius decreasing. It is also shown that the amplitude of the radial motion for bubbles decreases with the increase of the tissue shear modulus and the frequency, when the ratio of bubble radius to the cavity radius is constant. The effect of the elasticity is very obvious, which reduces the amplitude greatly. The effect of elasticity will be less when the driving pressure is strong. It is found that the inertial cavitation threshold of bubble is relatively low in a range of 1–5 μm. The inertial cavitation threshold of bubble increases with the increase of shear modulus and driving frequency. The smaller the cavity radius, the higher the inertial cavitation threshold of the bubble is. This report aims to provide a firm theoretical basis for the future study of bubbles in a liquid-filled cavity surrounded by a viscoelasticity tissue.

The influence of droplet concentration on phase change and inertial cavitation thresholds associated with acoustic droplet vaporization.

Acoustic droplet vaporization (ADV) is an important process that enables the theragnostic application of acoustically activated droplets, where the nucleation of inertial cavitation (IC) activity must be precisely controlled. This Letter describes threshold pressure measurements for ADV and acoustic emissions consistent with IC activity of lipid-shelled non-superheated perfluoropentane nanodroplets over a range of physiologically relevant concentrations at 1.1-MHz. Under the frequency investigated, results show that the thresholds were relatively independent of concentration for intermediate concentrations (105, 106, and 107 droplets/ml), thus indicating an optimal range of droplet concentrations for conducting threshold studies. For the highest concentration, the difference between the threshold for IC and the threshold for ADV was greatly reduced, suggesting that it might prove difficult to induce ADV without concomitant IC in applications that employ higher concentrations.

Acoustic droplet vaporization threshold of perfluorocarbon droplets as a function of frequency: Effects of droplet cores and size

Phase shift liquid perfluorocarbon (PFC) droplets vaporizable by ultrasound can be used for many therapeutic and diagnostic applications. The ultrasound activation pressure required for the phase change of these droplets into echogenic microbubbles is termed acoustic droplet vaporization (ADV) threshold. We have studied the ADV and IC (inertial cavitation) thresholds in a tubeless setup using an acoustic means varying frequency of the excitation, the droplet core and their average size. The ADV threshold was found to increase with the increasing frequency for the lowest boiling point liquid, perfluoropentane (PFP), for both large and small average size droplets. For higher boiling point liquids, perfluorohexane (PFH) and perfluorooctyle bromide (PFOB), this study did not detect vaporization for small size droplets at the excitation levels (maximum 4 MPa peak negative) studied here. The large PFOB droplets experienced ADV only at the highest excitation frequency 15 MHz. For large PFH droplets, ADV threshold decreases with frequency that could possibly be due to the superharmonic focusing being a significant effect at larger sizes and the higher excitation pressures. ADV thresholds at all the frequencies studied here occurred at lower rarefactional pressures than IC thresholds indicating that phase transition precedes inertial cavitation.

Acoustic droplet vaporization embedded in 3-D printed gelatin methacrylate hydrogels

Gelatin Methacrylate (GelMA) is a popular hydrogel used for tissue engineering applications due to its biocompatibility, tunable mechanical properties, and rapid reproducibility. With its ability to be crosslinked with ultraviolet light exposure, GelMA can be 3-D printed into a variety of different shapes and geometries for customization for patient needs. We embedded phase-shift perfluorocarbon nanodroplets within the GelMA resin prior to 3-D printing. The droplets were then vaporized by external acoustic excitations determining the acoustic droplet vaporization (ADV) and inertial cavitation (IC) thresholds of the embedded droplets. The ADV of embedded droplets in a tissue engineering scaffolds can be used for triggered release of droplet contents. Varying the size and liquid core composition of the droplets as well as the mechanical properties of GelMA, one can change the ADV and IC characteristics of the embedded droplets. We will present the results of our experiments and discuss their implications on the potential use of this technology in tissue engineering.