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Background: Combined with thrombolytic drugs and/or microbubbles, ultrasound (US) has been regarded as a useful tool for thrombolysis treatment by taking its advantages of noninvasive, non‐ionization, low cost, and accurate targeting of tissues deep in body. Recently, low‐intensity pulsed US, which can cause fewer complications by stable cavitation and acoustic streaming other than more violent effects, has attracted broad attention. Purpose: However, the thrombolysis effect in practice might not achieve expectation because there is not an ideal parallel multilayered structure between the skin and the targeted vessel. Therefore, the current work aims to better elucidate the influence of US incident angle on the generation of acoustic streaming and thrombolysis effect. Methods: Systemic numerical and experimental studies, namely, finite element modeling (FEM), particle image velocimetry (PIV), and in vitro thrombolysis measurements, were performed to estimate the acoustical/streaming field pattern, maximum flow velocity, and shear stress on the surface of thrombus, as well as the lysis rate generated at different conditions. These methods aim at verifying the hypothesis that streaming‐induced vortices can further accelerate the dissolution of the thrombus and optimized thrombolysis effected can be achieved by adjusting US incident angles. Results: The pool data results showed that the variation trends of the flow velocity and shear stress obtained from FEM simulation and PIV experiments are qualitatively consistent with each other. There exists an optimal incident angle that can maximize the flow velocity and shear stress on the surface of thrombus, so that superior stirring and mixing effect can be generated. Furthermore, as the flow velocity and shear stress on thrombus surface are both highly correlated with the thrombolysis effect (the correlation coefficient R1 = 0.988, R2 = 0.958, respectively), the peak value of lysis rate (increase by at least 5.02%) also occurred at 10°. Conclusions: The current results demonstrated that, with appropriately determined incident angle, higher thrombolysis rate could be achieved without increasing the driving pressure. It may shed the light on future US thrombolysis planning strategy that, if combined with other advanced technologies (e.g., machine‐learning‐based image analysis and image‐guided adaptive US emission modulation), more efficient thrombolytic effect could be realized while minimizing undesired side‐effects caused by excessively high pressure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Percutaneous ethanol ablation (PEA) is an effective method for treating small liver cancer. Microbubble-enhanced ultrasound (MEUS) can potentially promote PEA by disrupting the tumour's circulation. In this study, treatment combining MEUS and PEA was performed to find any synergistic effects in tumour ablation.Methods: Ten rats bearing subcutaneous Walker-256 tumours were treated by MEUS combined with PEA. The other 18 tumour-bearing rats that were treated by MEUS or PEA served as the controls. MEUS was conducted by therapeutic ultrasound (TUS) and microbubble injection. TUS was operated at a frequency of 831 KHz with a pressure amplitude of 4.3 MPa. Tumour blood perfusion was assessed by contrast-enhanced ultrasound (CEUS), and the tumour necrosis rate was determined by histological examination.Results: CEUS showed that the tumour blood perfusion almost vanished in all of the MEUS-treated tumours. The contrast peak intensity dropped 84.8 % in the MEUS + PEA-treated tumours when compared to 46.3 % (p < 0.05) in the PEA-treated tumours 24 h after treatment. The tumour necrosis rate of the combination therapy was 97.50 %, which is much higher than that of the MEUS- (66.2 %) and PEA-treated (81.0 %) tumours.Conclusion: PEA combined with MEUS can induce a much more complete tumour necrosis.Key Points: • This experiment demonstrated a novel method for enhancing percutaneous ethanol ablation. • Microbubble-enhanced therapeutic ultrasound is capable of disrupting tumour circulation. • Combined therapy of MEUS and PEA can induce more complete necrosis of tumours. [ABSTRACT FROM AUTHOR]

Multi-parameter fitting algorithms, which are currently used for the characterization of coated-bubbles, inevitably introduce uncertainty into the results. Therefore, a better technique that can accurately determine the microbubbles׳ mechanical properties is urgently needed. A comprehensive technology combining atomic force microscopy, optical, and acoustic measurements with simulations of coated-bubble dynamics was developed. Using this technique, the mechanical parameters (size distribution, shell thickness, elasticity, and viscosity) of hybrid (ultrasound/magnetic-resonance-imaging) contrast microbubbles and their structure–property relationship were determined. The measurements indicate that when more superparamagnetic iron oxide nanoparticles are embedded in the microbubbles׳ shells, their mean diameter and effective viscosity increase, and their elastic modulus decreases. This reduces the microbubbles׳ resonance frequency and thus enhances acoustic scattering and attenuation effects. [ABSTRACT FROM AUTHOR]

The inertial cavitation (IC) activity of ultrasound contrast agents (UCAs) plays an important role in the development and improvement of ultrasound diagnostic and therapeutic applications. However, various diagnostic and therapeutic applications have different requirements for IC characteristics. Here through IC dose quantifications based on passive cavitation detection, IC thresholds were measured for two commercialized UCAs, albumin-shelled KangRun® and lipid-shelled SonoVue® microbubbles, at varied UCA volume concentrations (viz., 0.125 and 0.25 vol. %) and acoustic pulse lengths (viz., 5, 10, 20, 50, and 100 cycles). Shell elastic and viscous coefficients of UCAs were estimated by fitting measured acoustic attenuation spectra with Sarkar's model. The influences of sonication condition (viz., acoustic pulse length) and UCA shell properties on IC threshold were discussed based on numerical simulations. Both experimental measurements and numerical simulations indicate that IC thresholds of UCAs decrease with increasing UCA volume concentration and acoustic pulse length. The shell interfacial tension and dilatational viscosity estimated for SonoVue (0.7 ± 0.11 N/m, 6.5 ± 1.01 × 10-8 kg/s) are smaller than those of KangRun (1.05 ± 0.18 N/m, 1.66 ± 0.38 × 10-7 kg/s); this might result in lower IC threshold for SonoVue. The current results will be helpful for selecting and utilizing commercialized UCAs for specific clinical applications, while minimizing undesired IC-induced bioeffects. [ABSTRACT FROM AUTHOR]

Acoustic cavitation plays a critical role in various biomedical applications. However, uncontrolled cavitation can lead to undesired damage to healthy tissues. Therefore, real-time monitoring and quantitative evaluation of cavitation dynamics is essential for understanding underlying mechanisms and optimizing ultrasound treatment efficiency and safety. The current research addressed the limitations of traditionally used cavitation detection methods by developing introduced an adaptive time-division multiplexing passive cavitation imaging (PCI) system integrated into a commercial diagnostic ultrasound platform. This new method combined real-time cavitation monitoring with B-mode imaging, allowing for simultaneous visualization of treatment progress and 2D quantitative evaluation of cavitation dosage within targeted area. An improved delay-and-sum (DAS) algorithm, optimized with a minimum variance (MV) beamformer, is utilized to minimize the side lobe effect and improve the axial resolution typically associated with PCI. In additional to visualize and quantitatively assess the cavitation activities generated under varied acoustic pressures and microbubble concentrations, this system was specifically applied to perform 2D cavitation evaluation for ultrasound thrombolysis mediated by different solutions, e.g. , saline, nanodiamond (ND) and nitrogen-annealed nanodiamond (N-AND). This research aims to bridge the gap between laboratory-based research systems and real-time spatiotemporal cavitation evaluation demands in practical uses. Results indicate that this improved 2D cavitation monitoring and evaluation system could offer a useful tool for comprehensive evaluating cavitation-mediated effects (e.g. , ultrasound thrombolysis), providing valuable insights into in-depth understanding of cavitation mechanisms and optimization of cavitation applications. [ABSTRACT FROM AUTHOR]

Sonoporation has been widely accepted as a significant tool for gene delivery as well as some bio-effects like hemolysis, bringing in high demands of looking into its underlying mechanism. A two-dimensional (2D) boundary element method (BEM) model was developed to investigate microbubble-cell interaction, especially the morphological and mechanical characteristics around the close-to-bubble point (CP) on cell membrane. Based on time evolution analysis of sonoporation, detailed information was extracted from the model for analysis, including volume expansion ratio of the bubble, areal expansion ratio of the cell, jet velocity and CP displacement. Parametric studies were carried out, revealing the influence of different ultrasound parameters ( i.e. , driving frequency and acoustic pressure) and geometrical configurations ( i.e. , bubble-cell distance and initial bubble radius). This model could become a powerful tool not only for understanding bubble-cell interactions, but also for optimizing the strategy of sonoporation, such that it could be safer and of higher efficiency for biological and medical studies especially in clinics. [ABSTRACT FROM AUTHOR]

• Opto-acoustical vaporization of GNP-loaded NDs was enhanced &controllable. • A model for opto-acoustical vaporization of GNP-loaded NDs was established. • Opto-acoustical vaporization threshold of GNP-loaded NDs was evaluated. • Localized heating effect contributed to vaporization threshold reduction. • Simulated and experimental results were compared and in qualitative agreement. Phase-changeable contrast agents have been proposed as a next-generation ultrasound contrast agent over conventional microbubbles given its stability, longer circulation time and ability to extravasate. Safe vaporization of nanodroplets (NDs) plays an essential role in the practical translation of ND applications in industry and medical therapy. In particular, the exposure parameters for initializing phase change as well as the site of phase change are concerned to be controlled. Compared to the traditional optical vaporization or acoustic droplet vaporization, this study exhibited the potential of using simultaneous, single burst laser and ultrasound incidence as a means of activating phase change of NDs to generate cavitation nuclei with reduced fluence and sound pressure. A theoretical model considering the laser heating, vapor cavity nucleation and growth was established, where qualitative agreement with experiment findings were found in terms of the trend of combined exposure parameters in order to achieve the same level of vaporization outcome. The results indicate that using single burst laser pulse and 10-cycle ultrasound might be sufficient to lower the exposure levels under FDA limit for laser skin exposure and ultrasound imaging. The combination of laser and ultrasound also provides temporal and spatial control of ND vaporization and cavitation nucleation without altering the sound field, which is beneficial for further safe and effective applications of phase-changeable NDs in medical, environmental, food processing and other industrial areas. [ABSTRACT FROM AUTHOR]

Abstract: One isoform of the vascular endothelial growth factor, VEGF165, has been reported to be a dominant mediator and regulator of angiogenic process, which plays an important role in treating cardiovascular diseases and chronically ischemic wounds. Branched polyethylenimine (bPEI) has been widely used as a non-viral delivery vector for gene therapy. Although bPEI-mediated DNA transfection efficiency can be raised by increasing the PEI nitrogen:DNA phosphate (N/P) ratio, cytotoxicity increases as well. In this study, the enhancement effect of microbubble inertial cavitation (IC) on bPEI-mediated VEGF165 transfection was investigated, in an effort to optimize transfection efficiency using low N/P ratios. HEK 293T cells, mixed with bPEI:VEGF165 complexes, were exposed to 1-MHz ultrasound pulses. The results show that: (1) IC activity induced by microbubble destruction can be quantified as an IC “dose” (ICD) and will increase with increasing acoustic driving pressure; (2) larger sonoporation pores can be generated by increasing ICD; (3) the transfection efficiency can be enhanced by increasing ICD until reaching a saturation level; and (4) microbubble IC activity has less cytotoxicity than bPEI, although a combinatorial effect of microbubble IC activity and bPEI could be observed on cell viability. The results suggest that, with appropriate ultrasound parameters, it is possible to optimize bPEI-mediated VEGF transfection efficiency using relatively low N/P ratios by employing ultrasound-induced microbubble inertial cavitation. [Copyright &y& Elsevier]

Melanoma could be extremely lethal due to its high invasiveness and rapid proliferation, which causes thousands of deaths worldwide every year. Because of the resistance of melanoma to chemo/radio/immunotherapy, effective treatment of melanoma remains a clinically unsolved puzzle. Some efforts have been made to utilize ultrasound (US) to control the migration of melanoma cells, but the underlying mechanism is still unclear. Here, the impact of US-induced microbubble (MB) cavitation on the migration and cell cycle arrest of A375 melanoma cells was studied. To quantitatively explore the relationship between US-activated MB activity and the changes of A375 cellular response, inertial cavitation dose (ICD) was evaluated at varied acoustic driving pressures and MB concentrations. The pool data results showed that A375 cells' migrating capacity slightly fluctuated till ICD reached a certain threshold (3000 V × μs) and declined rapidly afterwards as the ICD further increased. Similar trend was observed in terms of the changes of G1-phase cell ratio. These findings suggested that, with appropriately selected parameters, MB-mediated cavitation can be effectively utilized to suppress the migration of A375 cells by reducing the proportion of cells arrested in G1 phase. [ABSTRACT FROM AUTHOR]

• General mechanisms underlying microbubble-mediated sonoporation are introduced. • Impacts of bubble/cell properties on bubble-cell interactions are reviewed. • Impacts of acoustic driving parameters on bubble-cell interactions are reviewed. • Impact of bubble/cell micro-environment on bubble-cell interactions are reviewed. • Clinical application and considerations of sonoporation are briefly reviewed. The past several decades have witnessed great progress in "smart drug delivery", an advance technology that can deliver genes or drugs into specific locations of patients' body with enhanced delivery efficiency. Ultrasound-activated mechanical force induced by the interactions between microbubbles and cells, which can stimulate so-called "sonoporation" process, has been regarded as one of the most promising candidates to realize spatiotemporal-controllable drug delivery to selected regions. Both experimental and numerical studies were performed to get in-depth understanding on how the microbubbles interact with cells during sonoporation processes, under different impact parameters. The current work gives an overview of the general mechanism underlying microbubble-mediated sonoporation, and the possible impact factors (e.g. , the properties of cavitation agents and cells, acoustical driving parameters and bubble/cell micro-environment) that could affect sonoporation outcomes. Finally, current progress and considerations of sonoporation in clinical applications are reviewed also. [ABSTRACT FROM AUTHOR]