Initial nucleation site formation due to acoustic droplet vaporization.
Ontology highlight
ABSTRACT:
SUBMITTER: Li DS
PROVIDER: S-EPMC3970834 | biostudies-other | 2014 Feb
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Acoustic droplet vaporization (ADV) is the selective vaporization of liquid microdroplets using ultrasound to produce stable gas bubbles. ADV is the primary mechanism in an ultrasound based cancer therapy, called gas embolotherapy, where the resulting bubbles are used to create localized occlusions leading to tumor necrosis. In this investigation, early time scale events including phase change are directly visualized using ultra-high speed imaging. Modulating elevated acoustic pressure or pulse length resulted in toroidal bubbles. For sufficiently short pulses (4 cycles at 7.5 MHz), toroidal bubble formation could be avoided, regardless of acoustic pressures tested.
| S-EPMC3965339 | biostudies-other
Project description:The challenge of translating pro-angiogenic growth factors for therapeutic purposes has stimulated a myriad of biomaterials-based, delivery approaches. Many techniques rely on incorporating a growth factor into a hydrogel. The kinetics of release can be tuned based on the physiochemical properties of the growth factor and scaffold. We have developed an acoustically-responsive scaffold (ARS), whereby release of a growth factor is non-invasively and spatiotemporally controlled in an on-demand manner using focused ultrasound. An ARS consists of a fibrin matrix doped with a growth factor-loaded, sonosensitive emulsion. In this study, we used an ARS to investigate the impact of basic fibroblast growth factor (bFGF) release on endothelial tubule formation. The co-culture model of angiogenic sprouting consisted of endothelial cell-coated microbeads and dispersed fibroblasts. bFGF release correlated with the acoustic pressure applied while sprout length correlated with both the volume of bFGF-loaded emulsion in the ARS and acoustic pressure. Minimal bFGF release and sprouting were observed in the absence of ultrasound exposure. Staggering the release of bFGF via multiple ultrasound exposures did not affect sprouting. Additionally, sprouting did not display a dependence on the distance between each microbead and the ARS. Overall, these results highlight the potential of using ultrasound to control regenerative processes via the controlled delivery of a growth factor. STATEMENT OF SIGNIFICANCE: Due to the ineffectiveness of conventional routes of administration, implantable hydrogels are often used as matrices to deliver growth factors (GFs). Spatial control of release is typically realized using anisotropic constructs while temporal control is obtained by modifying matrix properties and GF-scaffold interactions. In this study, we demonstrate how focused ultrasound can be used to non-invasively and spatiotemporally control release of basic fibroblast growth factor (bFGF), in an on-demand manner, from a composite hydrogel. The acoustically-responsive scaffold (ARS) consists of a bFGF-loaded, monodispersed double emulsion embedded within a fibrin matrix. We demonstrate how controlled release of bFGF can stimulate endothelial network formation. These results may be of interest to groups working on controlled release strategies for GFs, especially in the context of stimulating angiogenesis.
| S-EPMC6801030 | biostudies-literature
Project description:One of the major challenges in developing acoustic droplet vaporization (ADV)-associated therapy as an effective and safe strategy is the precise determination of the spatial cellular bioeffects after ADV (cell death or cell membrane permeabilization). In this study, we combined high-speed camera imaging and live-cell microscopic imaging to observe the transient dynamics of droplets during ADV and to evaluate the mechanical force on cells. Methods: C6 glioma cells were co-incubated with DiI-labeled droplets (radius: 1.5, 2.25, and 3.0 ?m). We used an acousto-optical system for high-speed bright-field (500 kfps) and fluorescence (40 kfps) microscopic imaging in order to visualize the dynamics of droplets under ultrasound excitation (frequency = 5 MHz, pressure = 5-8 MPa, cycle number = 3, pulse number = 1). Live-cell microscopic imaging was used to monitor the cell morphology, cell membrane permeabilization, and cell viability by membrane-anchored Lyn-yellow fluorescence protein, propidium Iodide staining, and calcein blue AM staining, respectively. Results: We discovered that the spatial distribution of ADV-induced bioeffects could be mapped to the physical dynamics of droplet vaporization. For droplets with a 1.5 ?m radius, the distance threshold for ADV-induced cell death (5.5±1.9 ?m) and reversible membrane permeabilization (11.3±3.5 ?m) was well correlated with the distance of ADV-bubble pressing downward to the floor (5.7±1.3 ?m) and maximum distance of droplet expansion (11.5±2.6 ?m), respectively. These distances were enlarged by increasing the droplet sizes and insonation acoustic pressures. The live-cell imaging results show that ADV-bubbles can directly disrupt the cell membrane layer and induce intensive intracellular substance leakage. Further, the droplets shed the payload onto nearby cells during ADV, suggesting ADV could directly induce adjacent cell death by physical force and enhancement of chemotherapy to distant cells. Conclusion: This study provide new insights into the ADV-mediated physicochemical synergic effect for medical applications.
| S-EPMC6276289 | biostudies-other
Project description:Acoustically sensitive emulsion droplets composed of a liquid perfluorocarbon have the potential to be a highly efficient system for local drug delivery, embolotherapy, or for tumor imaging. The physical mechanisms underlying the acoustic activation of these phase-change emulsions into a bubbly dispersion, termed acoustic droplet vaporization, have not been well understood. The droplets have a very high activation threshold; its frequency dependence does not comply with homogeneous nucleation theory and localized nucleation spots have been observed. Here we show that acoustic droplet vaporization is initiated by a combination of two phenomena: highly nonlinear distortion of the acoustic wave before it hits the droplet and focusing of the distorted wave by the droplet itself. At high excitation pressures, nonlinear distortion causes significant superharmonics with wavelengths of the order of the droplet size. These superharmonics strongly contribute to the focusing effect; therefore, the proposed mechanism also explains the observed pressure thresholding effect. Our interpretation is validated with experimental data captured with an ultrahigh-speed camera on the positions of the nucleation spots, where we find excellent agreement with the theoretical prediction. Moreover, the presented mechanism explains the hitherto counterintuitive dependence of the nucleation threshold on the ultrasound frequency. The physical insight allows for the optimization of acoustic droplet vaporization for therapeutic applications, in particular with respect to the acoustic pressures required for activation, thereby minimizing the negative bioeffects associated with the use of high-intensity ultrasound.
| S-EPMC3918756 | biostudies-other
Project description:Acoustic droplet vaporization is investigated in a theoretical model. This work is motivated by gas embolotherapy, a developmental cancer treatment involving tumor infarction with gas microbubbles that are selectively formed from liquid droplets. The results indicate that there exists a threshold value for initial droplet size below which the bubble evolution is oscillatory and above which it is smooth and asymptotic, and show that the vaporization process affects the subsequent microbubble expansion. Dampening of the bubble expansion is observed for higher viscosity and surface tension, with effects more pronounced for droplet size less than 6 mum in radius.
| S-EPMC2862051 | biostudies-other
Project description:Localized delivery of nucleic acids to target sites (e.g., diseased tissue) is critical for safe and efficacious gene therapy. An ultrasound-based technique termed acoustic droplet vaporization (ADV) has been used to spatiotemporally control the release of therapeutic small molecules and proteins contained within sonosensitive emulsions. Here, ADV is used to control the release of lipoplex-containing plasmid DNA encoding an enhanced green fluorescent protein reporter-from a sonosensitive emulsion. Focused ultrasound (3.5 MHz, mechanical index (MI) ? 1.5) generates robust release of fluorescein (i.e., surrogate payload) and lipoplex from the emulsion. In situ release of the lipoplex from the emulsion using ADV (MI = 1.5, 30 cycles) yields a 55% release efficiency, resulting in 43% transfection efficiency and 95% viability with C3H/10T1/2 cells. Without exposure to ultrasound, the release and transfection efficiencies are 5% and 7%, respectively, with 99% viability. Lipoplex released by ADV retains its bioactivity while the ADV process does not yield any measureable sonoporative enhancement of transfection. Co-encapsulation of Ficoll PM 400 within the lipoplex-loaded emulsion, and its subsequent release using ADV, yield higher transfection efficiency than the lipoplex alone. The results demonstrate that ADV can have utility in the spatiotemporal control of gene delivery.
| S-EPMC4956527 | biostudies-literature
Project description:Drug penetration influences the efficacy of tumor therapy. Although the leaky vessels of tumors can improve the penetration of nanodrugs via the enhanced permeability and retention (EPR) effect, various aspects of the tumor microenvironment still restrict this process. This study investigated whether vascular disruption using the acoustic vaporization of micro- or nanoscale droplets (MDs or NDs) induced by ultrasound sonication can overcome the limitations of the EPR effect to allow drug diffusion into extensive regions. The intravital penetration of DiI-labeled liposomes (as a drug model with red fluorescence) was observed using an acousto-optical integrated system comprising a 2-MHz focused ultrasound transducer (transmitting a three-cycle single pulse and a peak negative pressure of 10 MPa) in a window-chamber mouse model. Histology images of the solid tumor were also used to quantify and demonstrate the locations where DiI-labeled liposomes accumulated. In the intravital image analyses, the cumulative diffusion area and fluorescence intensity at 180 min were 0.08±0.01 mm(2) (mean±standard deviation) and 8.5±0.4%, respectively, in the EPR group, 0.33±0.01 mm(2) and 13.1±0.4% in the MD group (p<0.01), and 0.63±0.01 mm(2) and 18.9±1.1% in the ND group (p<0.01). The intratumoral accumulations of DiI-labeled liposomes were 1.7- and 2.3-fold higher in the MD and ND groups, respectively, than in the EPR group. These results demonstrate that vascular disruption induced by acoustic droplet vaporization can improve drug penetration more than utilizing the EPR effect. The NDs showed longer lifetime in vivo than MDs and provided potential abilities of long periods of treatment, intertissue ND vaporization, and intertissue NDs-converted bubble cavitation to improve the drug penetration and transport distance.
| S-EPMC4737725 | biostudies-literature
Project description:Acoustically-responsive scaffolds (ARSs), which are fibrin hydrogels containing monodispersed perfluorocarbon (PFC) emulsions, respond to ultrasound in an on-demand, spatiotemporally-controlled manner via a mechanism termed acoustic droplet vaporization (ADV). Previously, ADV has been used to control the release of bioactive payloads from ARSs to stimulate regenerative processes. In this study, we used classical nucleation theory (CNT) to predict the nucleation pressure in emulsions of different PFC cores as well as the corresponding condensation pressure of the ADV-generated bubbles. According to CNT, the threshold bubble radii above which ADV-generated bubbles remain stable against condensation were 0.4 µm and 5.2 µm for perfluoropentane (PFP) and perfluorohexane (PFH) bubbles, respectively, while ADV-generated bubbles of any size in perfluorooctane (PFO) condense back to liquid at ambient condition. Additionally, consistent with the CNT findings, stable bubble formation from PFH emulsion was experimentally observed using confocal imaging while PFO emulsion likely underwent repeated vaporization and recondensation during ultrasound pulses. In further experimental studies, we utilized this unique feature of ADV in generating stable or transient bubbles, through tailoring the PFC core and ultrasound parameters (excitation frequency and pulse duration), for sequential delivery of two payloads from PFC emulsions in ARSs. ADV-generated stable bubbles from PFH correlated with complete release of the payload while transient ADV resulted in partial release, where the amount of payload release increased with the number of ultrasound exposure. Overall, these results can be used in developing drug delivery strategies using ARSs.
| S-EPMC7803826 | biostudies-literature
Project description:One application of acoustic droplet vaporization (ADV), a method of converting biocompatible microdroplets into microbubbles, is to enhance locally high intensity focused ultrasound (HIFU) therapy. Two objectives are pursued here: (1) the controlled creation of a bubble trench prior to HIFU using ADV and (2) use of the trench for increasing ablation volumes, lowering acoustic powers, and decreasing therapy duration. Thermally responsive phantoms were made with perfluorocarbon emulsion. Compound lesions were formed in a laboratory setting and a clinical magnetic resonance imaging (MRI)-guided HIFU system. Linear and spiral patterned compound lesions were generated in trenches. A larger fraction of the HIFU beam is contained to increase the generation of heat. Using the laboratory system, a 90 mm linear length spiral trench was formed in 30 s with mechanical beam steering. Comparatively, the clinical HIFU system formed a 19.9 mm linear length spiral trench in approximately 1 s with electronic beam steering. Lesions were imaged optically and with MRI. A uniform thermal ablation volume of 3.25 mL was achieved in 55.4 s (4-times faster than standard clinical HIFU and 14-times larger volume versus sum of individual lesions). Single lesions showed a 400% volume increase.
| S-EPMC3985868 | biostudies-other
Project description:Acoustic droplet vaporization (ADV) has been shown to reduce the partial pressure of oxygen (PO2) in a fluid. The goals of this study were three-fold: 1) to determine the ADV pressure amplitude threshold in fluids that had physiologically relevant values for surface tension, protein concentration, and viscosity; 2) to assess whether these parameters and fluid mixing affect ADV-mediated PO2 reduction; and 3) to assess the feasibility of ADV-mediated PO2 reduction in plasma and whole blood. In vitro ADV experiments were conducted using perfluoropentane droplets (number density: 5?×?106?±?0.2?×?106/mL) dispersed in fluids (saline, polyvinylpyrrolidone solutions, porcine plasma, or porcine whole blood) that had a physiological range of surface tensions (62-68?mN/m), protein concentrations (0 and 68.7?mg/mL), and viscosities (0.7-4 cP). Droplets were exposed to pulsed ultrasound (5?MHz, 4.25?MPa peak negative pressure) while passing through a 37?°C flow system with inline PO2 sensors. In select experiments, the fluid also passed through mixing channels after ultrasound exposure. Our results revealed that the ADV pressure thresholds were the same for all fluids. Surface tension and protein concentration had no effect on PO2 reduction. Increasing viscosity attenuated PO2 reduction. However, the attenuated effect was absent after fluid mixing. Furthermore, ADV-mediated PO2 reduction in whole blood (30.8?±?3.2?mmHg) was less than that in a polyvinylpyrrolidone solution (40.2?±?2.1?mmHg) with equal viscosity. These findings should be considered when planning clinical studies of ADV-mediated PO2 reduction and other biomedical applications of ADV.
| S-EPMC6659737 | biostudies-literature