Search

Coated microbubbles are widely used in medical applications, particularly in enhanced drug and gene delivery. One of the mechanisms underlying these applications involves the shear stress exerted on the cell membrane by acoustic microstreaming generated through cavitation bubbles. In this study, we develop a novel simulation approach that combines the smooth dissipative particle dynamics (SDPD) simulation method with numerical modeling of the Rayleigh–Plesset-like equation in an ad hoc manner to simulate stable cavitation of microbubbles at microsecond and micrometer scales. Specifically, the SDPD method is utilized to model fluid dynamics, while the Rayleigh–Plesset-like equation is employed to describe bubble dynamics. Adopting a 1.5 μm coated microbubble driven by ultrasound with a frequency of 2 MHz and a pressure of 500 kPa as a representative example, we observe a high-velocity microstreaming pattern emerging around the bubble on a very small scale of a few micrometers after only a few microseconds. These spatiotemporal scales may pose challenges for experimental observation. The formation of this microstreaming arises from the opposing motion of the fluid layer next to the bubble and the fluid layers further away. Furthermore, our simulations reveal high shear stress levels of thousands of Pascals exerted on a wall located a few micrometers from the bubble. This contrasts with the shear stress values of a few Pascals calculated from theoretical models in the literature, which do not incorporate radial streaming into their theories. The implications of our results for bubble cavitation-induced pore formation on the cell membrane are discussed in some details. [ABSTRACT FROM AUTHOR]

In this study, the round-trip motion of air-rich bubbles exhaled from a water vapor-rich bubble was investigated. The local heating of non-degassed water produced a vapor-rich bubble with a maximum diameter of 9 μ m, which intermittently exhaled air-rich bubbles with a radius of less than 1 μ m. The exhaled air-rich bubbles initially moved away from the heat source; however, as the air-rich bubbles fused and grew larger, they returned to the heat source and fused with the vapor-rich bubble. This round-trip motion of the air-rich bubbles is explained by the balance between the Marangoni and quasi-steady drag forces induced on the bubbles. As the quasi-steady drag force is approximately proportional to the bubble radius and the Marangoni force is proportional to the square of the bubble radius, a larger bubble correlates with a greater effect of the Marangoni force. To produce a quasi-steady drag force that can balance the increased Marangoni force, air-rich bubbles were attracted to the heat source against the flow created by the vapor-rich bubble. These results provide insight into the stabilization of water-vapor-rich microbubbles in non-degassed water, which can generate strong flows on the order of 1 m/s. [ABSTRACT FROM AUTHOR]

Recently, we demonstrated that the local heating of degassed water can generate water vapor microbubbles and induce a rapid flow around the bubble. Although flow generation involves the self-excited oscillation of bubbles at a local heating point, the conditions under which the bubbles oscillate are not fully understood. In this study, the dependence of microbubble size and oscillation frequency on the concentration of non-condensable gases in water was investigated. A continuous-wave laser beam was focused on a β -FeSi 2 thin film, and water was locally heated using the photothermal conversion properties of the film. The results showed that the lower the concentration of non-condensable gases dissolved in water, the smaller the bubble size and the higher the oscillation frequency. Furthermore, it was found that the bubbles oscillate when the amount of non-condensable gas absorbed by the bubbles, i.e., the bubble size, falls below a specific level. This study can provide a new understanding of the bubble oscillation mechanism and lead to the development of fluid control technology using bubbles. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations in the microcanonical ensemble are performed to study the collapse of a bubble in liquid water using the single-site mW and the four-site TIP4P/2005 water models. To study system size effects, simulations for pure water systems are performed using periodically replicated simulation boxes with linear dimensions, L, ranging from 32 to 512 nm with the largest systems containing 8.7 × 106 and 4.5 × 109 molecules for the TIP4P/2005 and mW water models, respectively. The computationally more efficient mW water model allows us to reach converging behavior when the bubble dynamics results are plotted in reduced units, and the limiting behavior can be obtained through linear extrapolation in L−1. Qualitative differences are observed between simulations with the mW and TIP4P/2005 water models, but they can be explained by the models' differences in predicted viscosity and surface tension. Although bubble collapse occurs on time scales of only hundreds of picoseconds, the system sizes used here are sufficiently large to obtain bubble dynamics consistent with the Rayleigh–Plesset equation when using the models' thermophysical properties as input. For the conditions explored here, extreme heating of the interfacial water molecules near the time of collapse is observed for the larger mW water systems (but the model underpredicts the viscosity), whereas heating is less pronounced for the TIP4P/2005 water systems because its larger viscosity contribution slows the collapse dynamics. The presence of nitrogen within the bubble only starts to affect bubble dynamics near the very end of the initial collapse, leading to an incomplete collapse and strong rebound for the mW water model. Although nitrogen is non-condensable at 300 K, it becomes highly compressed and reaches a liquid-like density near the collapse point. We find that the dissolution of nitrogen is much slower than the movement of the collapsing water front, and the re-expansion of the dense nitrogen droplet gives rise to bubble rebound. The incompatibility of the collapse and dissolution time scales should be considered for continuum-scale modeling of bubble dynamics. We also confirm that the diffusion coefficient for dissolved nitrogen is insensitive to pressure as the liquid transitions from a compressed to a stretched state. [ABSTRACT FROM AUTHOR]

Rationale: Microbubble (MB) contrast agents combined with ultrasound targeted microbubble cavitation (UTMC) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (EGFR), to squamous cell carcinoma (SCC) via a novel MB-liposome complex (LPX). Methods: LPXs were constructed by conjugation of cationic liposomes to the surface of C4F10 gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction. Luciferase-expressing SCC-VII cells (SCC-VII-Luc) were cultured in Petri dishes. The Petri dishes were filled with media in which LPXs loaded with siRNA against firefly luciferase (Luc siRNA) were suspended. Ultrasound (US) (1 MHz, 100-µs pulse, 10% duty cycle) was delivered to the dishes for 10 sec at varying acoustic pressures and luciferase assay was performed 24 hr later. In vivo siRNA delivery was studied in SCC-VII tumor-bearing mice intravenously infused with a 0.5 mL saline suspension of EGFR siRNA LPX (7×108 LPX, ~30 µg siRNA) for 20 min during concurrent US (1 MHz, 0.5 MPa spatial peak temporal peak negative pressure, five 100-µs pulses every 1 ms; each pulse train repeated every 2 sec to allow reperfusion of LPX into the tumor). Mice were sacrificed 2 days post treatment and tumor EGFR expression was measured (Western blot). Other mice (n=23) received either EGFR siRNA-loaded LPX + UTMC or negative control (NC) siRNA-loaded LPX + UTMC on days 0 and 3, or no treatment (sham). Tumor volume was serially measured by high-resolution 3D US imaging. Results: Luc siRNA LPX + UTMC caused significant luciferase knockdown vs. no treatment control, p

Introduction Methods Results Conclusions Primarily used as ultrasound contrast agents, microbubbles have recently emerged as a versatile therapeutic vector that can be ‘burst’ to deliver payloads in the presence of suitably optimised ultrasound fields. Ultrasound‐stimulated microbubbles (USMB) have recently demonstrated improvements in treatment outcomes across a variety of clinical applications. This scoping review investigates whether this potential translates into the context of radiation therapy by evaluating the application of this technology across all three phases of radiation action.Primary research articles, excluding poster presentations and conference proceedings, were identified through systematic searches of the PubMed NCBI/Medline, Embase/OVID, Web of Science and CINAHL/EBSCOhost databases, with additional articles identified via manual Google Scholar searching. Articles were dual screened for inclusion using the Covidence systematic review platform and classified against all three phases of radiation action.Overall, 57 eligible publications from a total of 1389 identified articles were included in the review, with studies dating back to 2012. Study heterogeneity prevented formal statistical analysis; however, most articles reported improved outcomes using USMB in the presence of radiation compared to that of radiation alone. These improvements appear to result from the use of USMB as either a biovascular disruptor causing tumour cell damage via indirect mechanisms, or as a localised treatment vector that directly increases tumour cell uptake of other therapeutic and physical agents designed to enhance radiation action.USMB demonstrate exciting potential to enhance the effects of radiation treatments due to their versatility and capacity to target all three phases of radiation action. [ABSTRACT FROM AUTHOR]

Molecular ultrasound imaging with actively targeted microbubbles (MB) proved promising in preclinical studies but its clinical translation is limited. To achieve this, it is essential that the actively targeted MB can be produced with high batch-to-batch reproducibility with a controllable and defined number of binding ligands on the surface. In this regard, poly (n-butyl cyanoacrylate) (PBCA)-based polymeric MB have been used for US molecular imaging, however, ligand coupling was mostly done via hydrolysis and carbodiimide chemistry, which is a multi-step procedure with poor reproducibility and low MB yield. Herein, we developed a single-step coupling procedure resulting in high MB yields with minimal batch-to-batch variation. Actively targeted PBCA-MB were generated using an aminolysis protocol, wherein amine-containing cRGD was added to the MB using lithium methoxide as a catalyst. We confirmed the successful conjugation of cRGD on the MB surface, while preserving their structure and acoustic signal. Compared to the conventional hydrolysis protocol, aminolysis resulted in higher MB yields and better reproducibility of coupling efficiency. Optical imaging revealed that under flow conditions, cRGD- and rhodamine-labelled MB, generated by aminolysis, specifically bind to tumor necrosis factor-alpha (TNF-α) activated endothelial cells in vitro. Furthermore, US molecular imaging demonstrated a markedly higher binding of the cRGD-MB than of control MB in TNF-α activated mouse aortas and 4T1 tumors in mice. Thus, using the aminolysis based conjugation approach, important refinements on the production of cRGD-MB could be achieved that will facilitate the production of clinical-scale formulations with excellent binding and ultrasound imaging performance. [ABSTRACT FROM AUTHOR]

Dynamic Ultrasound Localization Microscopy (DULM) has first been developed for non-invasive Pulsatility measurements in the rodent brain. DULM relies on the localization and tracking of microbubbles (MBs) injected into the bloodstream, to obtain highly resolved velocity and density cine-loops. Previous DULM techniques required ECG-gating, limiting its application to specific datasets, and increasing acquisition time. The objective of this study is to eliminate the need for ECG-gating in DULM experiments by introducing a motion-matching method for time registration. We developed a motion-matching algorithm based on tissue Doppler that leverages the cyclic tissue motion within the brain. Tissue Doppler was estimated for each group of frames in the acquisitions, at multiple locations identified as local maxima in the skin above the skull. Subsequently, each group of frames was time-registered to a reference group by delaying it based on the maximum correlation value between their respective tissue Doppler signals. This synchronization ensured that each group of frames aligned with the brain tissue motion of the reference group, and consequently, with its cardiac cycle. As a result, velocities of MBs could be averaged to retrieve flow velocity variations over time. Initially validated in ECG-gated acquisitions in a rat model (n = 1), the proposed method was successfully applied in a mice model in 2D (n = 3) and in a feline model in 3D (n = 1). Performing time-registration with the proposed motion-matching method or by using ECG-gating leads to similar results. For the first time, dynamic velocity and density cine-loops were extracted without the need for any information on the animal ECG, and complex dynamic markers such as the Pulsatility index were estimated. Results suggest that DULM can be performed without external gating, enabling the use of DULM on any ULM dataset where enough MBs are detectable. Time registration by motion-matching represents a significant advancement in DULM techniques, making DULM more accessible by simplifying its experimental complexity. [ABSTRACT FROM AUTHOR]

Both microbubble ultrasound contrast agents and acoustic phase change droplets (APCD) have been explored in hepatocellular carcinoma (HCC). This work aimed to evaluate changes to the HCC microenvironment following either microbubble or APCD destruction in a syngeneic pre-clinical model. Mouse RIL-175 HCC tumors were grown in the right flank of 64 immunocompetent mice. Pre-treatment, photoacoustic volumetric tumor oxygenation, and power Doppler measurements were obtained using a Vevo 3100 system (VisualSonics, Toronto, Canada). The experimental groups received a 0.1 mL bolus injection of either Definity ultrasound contrast agent (Lantheus Medical Imaging) or APCD fabricated by condensing Definity. Following injection, ultrasound destruction was performed using flash-replenishment sequences on a Sequoia with a 10L4 probe (Siemens) for the duration of enhancement. Tumor oxygenation and power Doppler measurements were then repeated immediately post-ultrasound treatment. Twenty-four hours post-treatment, animals were euthanized, and tumors were harvested and stained for CD31, Cleaved Caspase 3 and CD45. Imaging biomarkers demonstrated a significant reduction in percent vascularity following either microbubble or APCD destruction in the tumor microenvironment (p < 0.022) but no significant changes in tumor oxygenation (p = 0.12). Similarly, immunohistochemistry data demonstrated a significant decrease in CD31 expression (p < 0.042) and an increase in apoptosis (p < 0.014) in tumors treated with destroyed microbubbles or APCD relative to controls. Finally, a significant increase in CD45 expression was observed in tumors treated with APCD (p = 0.046), indicating an increase in tumor immune response. Ultrasound-triggered destruction of both microbubbles and APCD reduces vascularity, increases apoptosis, and may also increase immune response in this HCC model. [ABSTRACT FROM AUTHOR]

Functionalized monodisperse microbubbles have the potential to boost the sensitivity and efficacy of molecular ultrasound imaging and targeted drug delivery using bubbles and ultrasound. Monodisperse bubbles can be produced in a microfluidic flow focusing device. However, their functionalization and sequential use require removal of the excess lipids from the bubble suspension to minimize the use of expensive ligands and to avoid competitive binding and blocking of the receptor molecules. To date, excess lipid removal is performed by centrifugation, which is labor intensive and challenging to automate. More importantly, as we show, the increased hydrostatic pressure during centrifugation can reduce bubble monodispersity. Here, we introduce a novel automated microfluidic 'washing' method. First, bubbles are injected in a microfluidic chamber 1 mm in height where they are left to float against the top wall. Second, lipid-free medium is pumped through the chamber to remove excess lipids while the bubbles remain located at the top wall. Third, the washed bubbles are resuspended and removed from the device into a collection vial. We demonstrate that the present method can (i) reduce the excess lipid concentration by 4 orders of magnitude, (ii) be fully automated, and (iii) be performed in minutes while the size distribution, functionality, and acoustic response of the bubbles remain unaffected. Thus, the presented method is a gateway to the fully automated production of functionalized monodisperse microbubbles. [ABSTRACT FROM AUTHOR]

Background: In recent years, with the rapid advancement of fundamental ultrasonography research, the application of ultrasound in disease treatment has progressively increased. An increasing body of research indicates that microbubbles serve not only as contrast agents but also in conjunction with ultrasound, enhancing cavitation effects and facilitating targeted drug delivery, thereby augmenting therapeutic efficacy. The objective of this study is to explore the current status and prevailing research trends in this field from 2009 to 2023 through bibliometric analysis and to forecast future developmental trajectories. Methods: We selected the Science Citation Index Expanded (SCI-Expanded) from the Web of Science Core Collection (WOSCC) as our primary data source. On 19 January 2024, we conducted a comprehensive search encompassing all articles and reviews published between 2009 and 2023 and utilized the bibliometric online analysis platform, CiteSpace and VOSviewer software to analyze countries/regions, institutions, authors, keywords, and references, used Microsoft Excel 2021 to visualize the trends of the number of articles published by year. Results: Between 1 January 2009, and 31 December 2023, 3,326 publications on ultrasound combined with microbubble therapy technology were included. There were a total of 2,846 articles (85.6%) and 480 reviews (14.4%) from 13,062 scholars in 68 countries/regions published in 782 journals. China and the United States emerged as the primary contributors in this domain. In terms of publication output and global institutional collaboration, the University of Toronto in Canada has made the most significant contribution to this field. Professor Kullervo Hynynen has achieved remarkable accomplishments in this area. Ultrasound in Medicine and Biology is at the core of the publishing of research on ultrasound combined with microbubble therapy technology. Keywords such as "sonodynamic therapy," "oxygen," "loaded microbubbles" and "Alzheimer's disease" indicate emerging trends in the field and hold the potential to evolve into significant areas of future investigation. Conclusion: This study provides a summary of the key contributions of ultrasound combined with microbubble therapy to the field's development over the past 15 years and delves into the historical underpinnings and contemporary trends of ultrasound combined with microbubble therapy technology, providing valuable guidance for researchers. [ABSTRACT FROM AUTHOR]

Contrast enhanced ultrasonography enables dynamic evaluation of the microvasculature down to the capillaries when using high resolution ultrasound probes. It's application in the evaluation of axillary lymph nodes in breast cancer patients with clinically negative axilla has been studied in 42 patients. The results of pre operative CEUS evaluation was correlated with histopathology status of axillary nodes after the harvesting of nodes during modified radical mastectomy or sentinel node biopsy. Heterogeneous enhancement with micro bubbles of the axillary nodes was found to be the most distinguishing criteria for malignant nodes. [ABSTRACT FROM AUTHOR]

This study investigates the tribological properties of resin composites reinforced with the fillers of glass powder and micro-bubbles. Resin composites were prepared with varying concentrations from 1% to 5% wt of fillers. Tribological tests were conducted using a block-on-ring scheme under dry friction conditions. The measurements of friction coefficient and wear values were performed under variable rotation speeds and loading conditions. The study showed that resin composites with 2–3% glass powder fillers and resin composites with 3–4% micro-bubbles exhibited optimal tribological properties. The resin glass powder modifications reduce the wear by 63% and resin micro-bubbles reduce wear by 32%. SEM analysis of the surfaces revealed surface imperfections and structural damage mechanisms, including abrasive and fatigue wear. The study concludes that specific filler concentrations improve the friction and wear resistance of resin composites, highlighting the importance of material preparation and surface quality in tribological performance. The increased wear resistance on both composites would hopefully expand the usage of additive manufactured composite, namely industrial moving components such as polymer gear, wheel, pulley, etc. [ABSTRACT FROM AUTHOR]

The internal pore structural characteristics and microbubble distribution features of concrete have a significant impact on its frost resistance, but their size is relatively small compared to aggregates, making them difficult to visually represent in the mesoscopic numerical model of concrete. Therefore, based on the ice-crystal phase transition mechanism of pore water and the theory of fine-scale inclusions, this paper establishes an estimation model for effective thermal conductivity and permeability coefficients that can reflect the distribution characteristics of the internal pore size and the content of microbubbles in porous media and explores the evolution mechanism of effective thermal conductivity and permeability coefficients during the freezing process. The segmented Gaussian integration method is adopted for the calculation of integrals involving pore size distribution curves. In addition, based on the concept that the fracture phase represents continuous damage, a switching model for the permeability coefficient is proposed to address the fundamental impact of frost cracking on permeability. Finally, the proposed estimation models for thermal conductivity and permeability are applied to the cement mortar and the interface transition zone (ITZ), and a thermal–hydraulic–mechanical coupling finite element model of concrete specimens at the mesoscale based on the fracture phase-field method is established. After that, the frost-cracking mechanism in ordinary concrete samples during the freezing process is explored, as well as the mechanism of microbubbles in relieving pore pressure and the adverse effect of accelerated cooling on frost cracking. The results show that the cracks first occurred near the aggregate on the concrete sample surface and then extended inward along the interface transition zone, which is consistent with the frost-cracking scenario of concrete structures in cold regions. [ABSTRACT FROM AUTHOR]

Administration of oxygen microbubbles (OMBs) has been shown to increase oxygen and decrease carbon dioxide in systemic circulation, as well as reduce lung inflammation and promote survival in preclinical models of hypoxia caused by lung injury. However, their impact on microenvironmental oxygenation remains unexplored. Herein, we investigated the effects of intraperitoneal administration of OMBs in anesthetized rats exposed to hypoxic ventilation (FiO2 = 0.14). Blood oxygenation and hemodynamics were evaluated over a 2 h time frame, and then organ and tissue samples were collected for hypoxic and metabolic analyses. Data showed that OMBs improved blood SaO2 (~14%) and alleviated tissue hypoxia within the microenvironment of the kidney and intestine at 2 h of hypoxia. Metabolomic analysis revealed OMBs induced metabolic differences in the cecum, liver, kidney, heart, red blood cells and plasma. Within the spleen and lung, principal component analysis showed a metabolic phenotype more comparable to the normoxic group than the hypoxic group. In the spleen, this shift was characterized by reduced levels of fatty acids and 2-hydroxygluterate, alongside increased expression of antioxidant enzymes such as glutathione and hypoxanthine. Interestingly, there was also a shuttle effect within the metabolism of the spleen from the tricarboxylic acid cycle to the glycolysis and pentose phosphate pathways. In the lung, metabolomic analysis revealed upregulation of phosphatidylethanolamine and phosphatidylcholine synthesis, indicating a potential indirect mechanism through which OMB administration may improve lung surfactant secretion and prevent alveolar collapse. In addition, cell-protective purine salvage was increased within the lung. In summary, oxygenation with intraperitoneal OMBs improves systemic blood and local tissue oxygenation, thereby shifting metabolomic profiles of the lung and spleen toward a healthier normoxic state. [ABSTRACT FROM AUTHOR]

Standard treatment for deep vein thrombosis (DVT) involves catheter-directed anticoagulants or thrombolytics, but the chronic thrombi present in many DVT cases are often resistant to this therapy. Histotripsy has been found to be a promising adjuvant treatment, using the mechanical action of cavitating bubble clouds to enhance thrombolytic activity. The objective of this study was to determine if histotripsy enhanced recombinant tissue plasminogen activator (rt-PA) thrombolysis in highly retracted porcine clots in vitro in a flow model of occlusive DVT. Highly retracted porcine whole blood clots were treated for 1 h with either catheter-directed saline (negative control), rt-PA (lytic control), histotripsy, DEFINITY and histotripsy or the combination of rt-PA and histotripsy with or without DEFINITY. Five-cycle, 1.5 MHz histotripsy pulses with a peak negative pressure of 33.2 MPa and pulse repetition frequency of 40 Hz were applied along the clot. B-Mode and passive cavitation images were acquired during histotripsy insonation to monitor bubble activity. Clots subjected to histotripsy with and without rt-PA exhibited greater thrombolytic efficacy than controls (7.0% flow recovery or lower), and histotripsy with rt-PA was more efficacious than histotripsy with saline (86.1 ± 10.2% compared with 61.7 ± 19.8% flow recovery). The addition of DEFINITY to histotripsy with or without rt-PA did not enhance either thrombolytic efficacy or cavitation dose. Cavitation dose generally did not correlate with thrombolytic efficacy. Enhancement of thrombolytic efficacy was achieved using histotripsy, with and without catheter-directed rt-PA, in the presence of physiologic flow. This suggests these treatments may be effective as therapy for DVT. [ABSTRACT FROM AUTHOR]

Ultrasound-triggered bubble-mediated local drug delivery has shown potential to increase therapeutic efficacy and reduce systemic side effects, by loading drugs into the microbubble shell and triggering delivery of the payload on demand using ultrasound. Understanding the behavior of the microbubbles in response to ultrasound is crucial for efficient and controlled release. In this work, the response of microbubbles with a coating consisting of poly(2-ethyl-butyl cyanoacrylate) (PEBCA) nanoparticles and denatured casein was characterized. High-speed recordings were taken of single microbubbles, in both bright field and fluorescence. The nanoparticle-loaded microbubbles show resonance behavior, but with a large variation in response, revealing a substantial interbubble variation in mechanical shell properties. The probability of shell rupture and the probability of nanoparticle release were found to strongly depend on microbubble size, and the most effective size was inversely proportional to the driving frequency. The probabilities of both rupture and release increased with increasing driving pressure amplitude. Rupture of the microbubble shell occurred after fewer cycles of ultrasound as the driving pressure amplitude or driving frequency was increased. The results highlight the importance of careful selection of the driving frequency, driving pressure amplitude and duration of ultrasound to achieve the most efficient ultrasound-triggered shell rupture and nanoparticle release of protein-and-nanoparticle–stabilized microbubbles. [ABSTRACT FROM AUTHOR]

The present study concerns the numerical modeling of microbubble oscillation within an elastic microvessel, aiming to enhance the safety and efficacy of ultrasound-mediated drug delivery and diagnostic imaging. The success of such applications depends on a thorough understanding of microbubble–vessel interactions. Despite some progress, the critical impact of the stabilizing shell around gas core has remained underexplored. To address this, we developed a novel numerical approach that models the stabilizing shell. Additionally, there is novelty in modeling consequent vascular deformation in response to complicated spatiotemporal microbubble oscillations. The novel approach was implemented for shear stress evaluation as a critical factor in vascular permeability. Finally, our unique approach offered novel insights into microbubble–vessel interactions under diverse acoustic conditions. Results indicated substantial impact of shell properties and acoustic parameters on induced shear stress. With a fourfold increase in acoustic pressure amplitude, 15.6-fold and sixfold increases were observed in maximum shear stress at 1 and 3 MHz , respectively. Also, the peak shear stress could reach up to 15.6 kPa for a shell elasticity of 0.2 N/m at 2.5 MHz. Furthermore, decreasing microvessel/bubble size ratio from 3 to 1.5 increased maximum shear stress from 5.1 to 24.3 kPa. These findings are crucial for optimizing ultrasound parameters in clinical applications, potentially improving treatment outcomes while minimizing risk of vessel damage. However, while our model demonstrated high fidelity in reproducing experimental observations, it is limited by assumptions of vessel geometry and homogeneity of vessel properties. Future work can improve our findings through in vitro experimental measurements. [ABSTRACT FROM AUTHOR]

The traditional wet-heating Maillard reaction (MR) used a long-duration process and affected the over-browning color of the product. Thus, ultrasound (UL) and microbubbles (MB) were studied to assist the traditional MR on cricket protein isolated (CPI) conjugated with fructooligosaccharide (FOS) called CPF. These processes were carried out using central composite design (CCD). Two independent variables were UL (2–58 min) and MB times (6–35 min). The significant variables WS, OHC, EAI and ESI, DPPH, ABTS, and FRAP were further optimized by the response surface method (RSM). RSM results showed that the quadratic model can predict response values. The optimal conditions yielded the most favorable functional properties (WS = 89.38 g/L, OHC = 8.65%, EAI = 81.37 m2/g, and ESI = 120.75 min) as well as the highest antioxidant activity (DPPH = 14.77, ABTS = 14.55, and FRAP = 13.98 µmol TE/g). Moreover, the UL and MB were not significantly affected by the browning index of CPF. This study can conclude that the UL and MB-assisted MR process is a promising method to decrease the processing time and is highly effective at improving the characteristics, functional properties, and antioxidant activity of conjugated cricket protein. [ABSTRACT FROM AUTHOR]

This review delves into the innovative technology of Blood-Brain Barrier (BBB) opening with low-intensity focused ultrasound in combination with microbubbles (LIFU-MB), a promising therapeutic modality aimed at enhancing drug delivery to the central nervous system (CNS). The BBB's selective permeability, while crucial for neuroprotection, significantly hampers the efficacy of pharmacological treatments for CNS disorders. LIFU-MB emerges as a non-invasive and localized method to transiently increase BBB permeability, facilitating the delivery of therapeutic molecules. Here, we review the procedural stages of LIFU-MB interventions, including planning and preparation, sonication, evaluation, and delivery, highlighting the technological diversity and methodological challenges encountered in current clinical applications. With an emphasis on safety and efficacy, we discuss the crucial aspects of ultrasound delivery, microbubble administration, acoustic feedback monitoring and assessment of BBB permeability. Finally, we explore the critical choices for effective BBB opening with LIFU-MB, focusing on selecting therapeutic agents, optimizing delivery methods, and timing for delivery. Overcoming existing barriers to integrate this technology into clinical practice could potentially revolutionize CNS drug delivery and treatment paradigms in the near future. [Display omitted] [ABSTRACT FROM AUTHOR]

Systemic drug administration provides convenience and non-invasive benefits for preventing and treating inner ear diseases. However, the blood-labyrinth barrier (BLB) restricts the transport of drugs to inner ear tissues. Ultrasound can stimulate specific areas and penetrate tissues, with the potential to overcome physiological barriers. We present a novel strategy based on low-pressure pulsed ultrasound assisted by microbubbles (USMB) to transiently open the BLB and deliver therapeutics into the inner ear. A pulsed ultrasound device with adjustable pressure was established; the generated ultrasound was transmitted through the external auditory canal into the guinea pig's inner ear. We observed that the application of microbubbles allowed the use of safe and efficient ultrasound conditions to penetrate the BLB. We found that USMB-mediated BLB opening seemed to be associated with a reduced expression of the tight junction proteins zonula occludens-1 and occludin. Following intravenous administration, hydrophilic dexamethasone sodium phosphate (DSP), hydrophobic curcumin (CUR), as well as drug-loaded nanoparticles (Fe 3 O 4 @CUR NPs) could be efficiently delivered into the inner ear. We observed better drug accumulation in the perilymph of the inner ear, resulting in less drug (cisplatin)-induced ototoxicity. Furthermore, physiological, hematological, and histological studies showed that the modulation of the BLB by low-pressure USMB was a safe process without significant adverse effects. We conclude that USMB could become a promising strategy for the systematic delivery of therapeutics in the treatment of inner ear diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

The tumor microenvironment is increasingly acknowledged as a critical contributor to cancer progression, mediating genetic and epigenetic alterations. Beyond diverse cellular interactions from the microenvironment, physicochemical factors such as tumor acidosis also significantly affect cancer dynamics. Recent research has highlighted that tumor acidosis facilitates invasion, immune escape, metastasis, and resistance to therapies. Thus, noninvasive measurement of tumor acidity and the development of targeted interventions represent promising strategies in oncology. Techniques like contrast-enhanced ultrasound (CEUS) can effectively assess blood perfusion, while ultrasound-stimulated microbubble cavitation (USMC) has proven to enhance tumor blood perfusion. We therefore aimed to determine whether CEUS assesses tumor acidity and whether USMC treatment can modulate tumor acidity. Firstly, we tracked CEUS perfusion parameters in MCF7 tumor models and compared them with in vivo tumor pH recorded by pH microsensors. We found that the peak intensity and area under curve of tumor contrast-enhanced ultrasound correlated well with tumor pH. We further conducted USMC treatment on MCF7 tumor-bearing mice, tracked changes of tumor blood perfusion and tumor pH in different perfusion regions before and after the USMC treatment to assess its impact on tumor acidity and optimize therapeutic ultrasound pressure. We discovered that USMC with 1.0 Mpa significantly improved tumor blood perfusion and tumor pH. Furthermore, tumor vascular pathology and PGI2 assays indicated that improved tumor perfusion was mainly due to vasodilation rather than angiogenesis. More importantly, analysis of glycolysis-related metabolites and enzymes demonstrated USMC treatment can reduce tumor acidity by reducing tumor glycolysis. These findings support that CEUS may serve as a potential biomarker to assess tumor acidity and USMC is a promising therapeutic modality for reducing tumor acidosis. [ABSTRACT FROM AUTHOR]

Temperature and dissolved gas availability are important parameters for the germination of saltmarsh plants. As a newly developed method to increase the dissolved gas availability, the microbubble technology has shown to increase the crop germination and seedling growth. However, the effects of microbubbles (MBs) on the germination of saltmarsh plants have not been studied. The aim of this study is to investigate the effects of the MBs on the germination of. in different temperatures (6, 12, 18, 24 and 30ºC). The highest germination percent was observed at 24ºC in MBs water. The germination percent at MBs were significantly higher than those at control, deionized water at 24ºC. The germination energy (GE) was significantly higher at 24 and 30ºC than at 6 and 12ºC in both deionized and MBs waters. The mean germination time (MGT) was significantly shorter at 24 and 30ºC than at 6 and 12ºC in both waters. However, no significant effects of MBs were observed in terms of GE and MGT. This study suggests that MBs improves the germination percent of S. malacosperma at the optimal temperature (24ºC), but GE and MGT were not affected by MBs but by temperature in S. malacosperma. [ABSTRACT FROM AUTHOR]

Spinel ZnCo2O4 is an important multi-functional material with wide applications, such as electrocatalytic oxygen evolution reaction. However, it still remains a challenge to synthesize ZnCo2O4 with complex morphologies by a simple synthetic method. Here, mesoporous ZnCo2O4 microbubbles with hollow structures have been successfully synthesized by a facile one-pot calcination at 400°C in air. The achieved ZnCo2O4 shows a hollow bubble-like microstructure constructed by mesoporous walls, which consist of small primary nanoparticles 9.8 nm in diameter. Although the synthesis route is template/surfactant-free, the pore-size distribution curve shows a sharp peak at 7.6 nm with a very narrow distribution. The specific surface area and pore volume were 68 m2/g and 0.21 cm3/g, respectively. Due to the greatly enhanced mass transfer, the mesoporous ZnCo2O4 microbubbles show attractive electrochemical activity for oxygen evolution reaction. [ABSTRACT FROM AUTHOR]

Microbubbles (MBs) combined with focused ultrasound (FUS) has emerged as a promising noninvasive technique to permeabilize the blood–brain barrier (BBB) for drug delivery into the brain. However, the safety and biological consequences of BBB opening (BBBO) remain incompletely understood. This study aims to investigate the effects of two parameters mediating BBBO: microbubble volume dose (MVD) and mechanical index (MI). High-resolution MRI-guided FUS was employed in mouse brains to assess BBBO by manipulating these two parameters. Afterward, the sterile inflammatory response (SIR) was studied 6 h post-FUS treatment. Results demonstrated that both MVD and MI significantly influenced the extent of BBBO, with higher MVD and MI leading to increased permeability. Moreover, RNA sequencing revealed upregulation of major inflammatory pathways and immune cell infiltration after BBBO, indicating the presence and extent of SIR. Gene set enrichment analysis identified 12 gene sets associated with inflammatory responses that were significantly upregulated at higher MVD or MI. A therapeutic window was established between therapeutically relevant BBBO and the onset of SIR, providing operating regimes to avoid damage from stimulation of the NFκB pathway via TNFɑ signaling to apoptosis. These results contribute to the optimization and standardization of BBB opening parameters for safe and effective drug delivery to the brain and further elucidate the underlying molecular mechanisms driving sterile inflammation. [ABSTRACT FROM AUTHOR]

A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications. [ABSTRACT FROM AUTHOR]

The document is a contents list for the journal "Lab on a Chip," which focuses on devices and applications at the micro- and nanoscale. It includes a range of articles on various topics, such as periodontal disease diagnosis, tissue barrier function, nucleic acid detection, cardiac muscle rings, and more. The journal aims to connect the world with the chemical sciences and is published by The Royal Society of Chemistry. [Extracted from the article]

Optofluidic regulation of blood microflow in vivo represents a significant method for investigating illnesses linked to abnormal changes in blood circulation. Currently, non-invasive strategies are limited to regulation within capillaries of approximately 10 μm in diameter because the adaption to blood pressure levels in the order of several hundred pascals poses a significant challenge in larger microvessels. In this study, using laser-induced microbubble formation within microvessels of the mouse auricle, we regulate blood microflow in small vessels with diameters in the tens of micrometers. By controlling the laser power, we can control the growth and stability of microbubbles in vivo. This controlled approach enables the achievement of prolonged ischemia and subsequent reperfusion of blood flow, and it can also regulate the microbubbles to function as micro-pumps for reverse blood pumping. Furthermore, by controlling the microbubble, narrow microflow channels can be formed between the microbubbles and microvessels for assessing the apparent viscosity of leukocytes, which is 76.9 ± 11.8 Pa·s in the in vivo blood environment. The proposed design of in vivo microbubble valves opens new avenues for constructing real-time blood regulation and exploring cellular mechanics within living organisms. [ABSTRACT FROM AUTHOR]

Poor mass transport to or from vertical gas-evolving electrodes can adversely impact energy efficiency and product purity in the production of hydrogen, chlorine, and various metals. A proper description that combines natural convection with micromixing of growing, coalescing, and departing bubbles is presently lacking. This work develops a simple, physically sound analytical model that includes the influence of bubble size, flow regime, and bubble surface coverage. By comprehensively reviewing mass transfer measurements from the water electrolysis literature, we observe that the surface coverage of oxygen bubbles increases much more strongly with increasing current density than an often-used square root scaling predicts. Strong differences are observed in the degree of micromixing of hydrogen and oxygen bubbles in alkaline and acidic electrolytes. These varied results can all be explained by a combination of electrocapillarity, and coalescence induced by either a high surface coverage or Marangoni flows. [Display omitted] • A simple formula for adding micromixing and natural convection is derived. • A single micromixing parameter between 0 and 5 describes all literature data. • Micromixing is strongest for oxygen in alkaline and hydrogen in acidic electrolytes. • Marangoni forces are attractive in this case, causing coalescence and larger bubbles. • Bubble coverage increases with the square/square root of current for oxygen/hydrogen. [ABSTRACT FROM AUTHOR]

This paper presents an innovative strategy to address the issues of clogging and cluster-related challenges in microchannels within microfluidic devices. Leveraging three-dimensional (3D) microbubble streaming as a dynamic solution, our approach involves the controlled activation of microbubbles near channel constrictions, inducing microstreaming with distinctive features. This microstreaming, characterized by a high non-uniform 3D gradient and significant shear stress, effectively inhibits arch formation at constrictions and disintegrates particle clusters, demonstrating real-time prevention of clogging incidents and blockages. This study includes experimental validation of the anti-clogging technique, a detailed examination of microstreaming phenomena, and their effects on clogging and clustering issues. It also incorporates statistical analyses performed in various scenarios to verify the method's effectiveness and adaptability. Moreover, a versatile control system has been designed that operates in event-triggered, continuous, or periodic modes, which suits different lab-on-a-chip applications and improves the overall functionality of microfluidic systems. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of microbubble degradation and flow velocity on Sub-Harmonic Aided Pressure Estimation (SHAPE), and to explore the correlation between subharmonic amplitude and pressure as a single factor. We develop an open-loop vascular phantom platform system and utilize a commercial ultrasound machine and microbubbles for subharmonic imaging. Subharmonic amplitude was measured continuously at constant pressure and flow velocity to assess the impact of microbubble degradation. Flow velocity was varied within a range of 4–14 cm/s at constant pressure to investigate its relationship to subharmonic amplitude. Furthermore, pressure was varied within a range of 10–110 mm Hg at constant flow velocity to assess its isolated effect on subharmonic amplitude. Under constant pressure and flow velocity, subharmonic amplitude exhibited a continuous decrease at an average rate of 0.221 dB/min, signifying ongoing microbubble degradation during the experimental procedures. Subharmonic amplitude demonstrated a positive correlation with flow velocity, with a variation ratio of 0.423 dB/(cm/s). Under controlled conditions of microbubble degradation and flow velocity, a strong negative linear correlation was observed between pressure and subharmonic amplitude across different Mechanical Index (MI) settings (all R2 > 0.90). The sensitivity of SHAPE was determined to be 0.025 dB/mmHg at an MI of 0.04. The assessment of SHAPE sensitivity is affected by microbubble degradation and flow velocity. Excluding the aforementioned influencing factors, a strong linear negative correlation between pressure and subharmonic amplitude was still evident, albeit with a sensitivity coefficient lower than previously reported values. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to apply spatiotemporal analysis of contrast-enhanced ultrasound (CEUS) loops to quantify the enhancement heterogeneity for improving the differentiation between benign and malignant breast lesions. Materials and methods: This retrospective study included 120 women (age range, 18–82 years; mean, 52 years) scheduled for ultrasound-guided biopsy. With the aid of brightness-mode images, the border of each breast lesion was delineated in the CEUS images. Based on visual evaluation and quantitative metrics, the breast lesions were categorized into four grades of different levels of contrast enhancement. Grade-1 (hyper-enhanced) and grade-2 (partly-enhanced) breast lesions were included in the analysis. Four parameters reflecting enhancement heterogeneity were estimated by spatiotemporal analysis of neighboring time-intensity curves (TICs). By setting the threshold on mean parameter, the diagnostic performance of the four parameters for differentiating benign and malignant lesions was evaluated. Results: Sixty-four of the 120 patients were categorized as grade 1 or 2 and used for estimating the four parameters. At the pixel level, mutual information and conditional entropy present significantly different values between the benign and malignant lesions (p < 0.001 in patients of grade 1, p = 0.002 in patients of grade 1 or 2). For the classification of breast lesions, mutual information produces the best diagnostic performance (AUC = 0.893 in patients of grade 1, AUC = 0.848 in patients of grade 1 or 2). Conclusions: The proposed spatiotemporal analysis for assessing the enhancement heterogeneity shows promising results to aid in the diagnosis of breast cancer by CEUS. Clinical relevance statement: The proposed spatiotemporal method can be developed as a standardized software to automatically quantify the enhancement heterogeneity of breast cancer on CEUS, possibly leading to the improved diagnostic accuracy of differentiation between benign and malignant lesions. Key Points: • Advanced spatiotemporal analysis of ultrasound contrast-enhanced loops for aiding the differentiation of malignant or benign breast lesions. • Four parameters reflecting the enhancement heterogeneity were estimated in the hyper- and partly-enhanced breast lesions by analyzing the neighboring pixel-level time-intensity curves. • For the classification of hyper-enhanced breast lesions, mutual information produces the best diagnostic performance (AUC = 0.893). [ABSTRACT FROM AUTHOR]

Developing affordable electrocatalysts is crucial for driving the sustainable energy transition to green hydrogen. Here, a generalizable method known as polymer infusion additive manufacturing is reported for transforming 3D‐printed photopolymers into core–shell micro lattice electrodes for electrocatalytic water splitting with transition metal/metal oxides/carbon heterointerfaces. The optimized free‐standing architectures integrate Cu/CuOx on carbon (Cu/CuOx/C) microlattices, yielding high electrocatalytic activity (overpotential of 145 mV at 10 mA cm−2 and a Tafel slope of 134 mV dec−1) and excellent durability for the hydrogen evolution reaction (HER) (>100 h), surpassing state‐of‐the‐art Cu foams. Additionally, for the oxygen evolution reaction (OER), Co/CoOx on carbon (Co/CoOx/C) microlattices display exceptional activity with the lowest overpotential (1.40 V to gain 10 mA cm−2) among all reported PGM‐free electrodes. The study explores the gas phase mass‐transport properties of these 3D microlattices via microscopic imaging of bubble evolution, finding that the outstanding electrocatalytic performance and long‐term stability of microlattice electrodes leverages their mesoscale (100–300 µm) pores, providing accessibility of electrolytes, maximizing utilization of active sites, and ensuring rapid evolution of gas bubbles. Thus, a simple but pioneering method is introduced for manufacturing 3D mesostructured electrocatalysts with deep control of liquid and gas phase mass‐transport, enhancing the efficacy of alkaline water electrolysis. [ABSTRACT FROM AUTHOR]

Objectives: Ultrasound‐targeted microbubble disruption (UTMD) is a widely used technique to improve the differentiation and proliferation capacity of mesenchymal stem cells (MSCs), but the optimal therapeutic parameters for UTMD are unclear. In this study, we aimed to find the appropriate peak negative pressure (PNP), which is a key parameter for enhancing the stemness properties and proliferation of MSCs. Methods: Experiments were performed in UTMD group, ultrasound (US) group under different PNP exposure conditions (0.5, 1.0, and 1.5 MPa), and control group. Apoptosis safety was analyzed by flow cytometry and MSC proliferation was measured at 12, 24, and 36 hours after irradiation by cell counting kit 8. The expression of the stemness genes NANOG, OCT‐4, and SOX‐2 were determined by enzyme‐linked immunosorbent assay (ELISA) or reverse transcription polymerase chain reaction. Results: The results showed that the 1.5 MPa UTMD‐treated group had the highest proliferation capacity of MSCs at 24 hours. ELISA or quantitative reverse transcription polymerase chain reaction results showed that UTMD treatment of the 1.5 MPa group significantly upregulated the expression of the stemness genes NANOG, SOX‐2, and OCT‐4. Conclusions: In conclusion, the appropriate peak PNP value of UTMD was 1.5 MPa, and 1.5 MPa‐mediated UTMD group obviously promoted MSCs proliferation and maintained stemness by upregulating the expression of stemness genes. [ABSTRACT FROM AUTHOR]

Flotation of small particles is one of the global challenges facing the mineral raw materials processing industry. Large amounts of non-ferrous and rare metals are lost in the flotation tailings in the form of mineral particles below 15 µm in size as a result of the low effectiveness of their capture by coarse bubbles generated in conventional flotation machines. The method of combined microflotation, developed in recent years, uses conventional coarse bubbles (CB) and microbubbles (MB) produced in the stand-alone generator of air-in-water microdispersion, which serves as the flotation carriers. Depending on the MB dose, the effect of their application may be positive or negative. The theoretical analysis of various mechanisms of particle transfer onto the surface of coarse bubbles and further into the froth layer allowed to obtain the formula for the optimal MB dose ƒ = dd/2dpρp, where dd is MB size; dp and ρp respectively are the size and the density of particles. Experiments performed on the copper ore flotation tailings at the Atalaya Mining (Spain) and Chaarat Kapan (Armenia) concentrators showed that, besides the optimal MB dose in the range of 1-3 ml/g, there is another optimal MB dose in the range of 10-20 ml/g, where the copper recovery increases by several percent compared to the reference test (ƒ = 0). The deep minimum in copper recovery is observed in the area between the optimal MB doses, which is by several percent lower than the value in the reference test. [ABSTRACT FROM AUTHOR]

Copyright of Chemical Engineering (China) / Huaxue Gongcheng is the property of Hualu Engineering Science & Technology Co Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The induced magnetic field is used to control the fluid motion and heat transfer in a variety of applications, such as in MHD devices, microfluidics, electrically conducting fluids in channels and in circular pipes, and clinical applications such as drug delivery and cooling of nuclear reactors. Henceforth this investigation aims to elucidate the behavior of viscoelastic (second-grade fluid) ternary nanofluid flow through a permeable stretching sheet with an induced magnetic field. The stretching surface is subjected to the Cattaneo-Christov heat and mass flux model to investigate heat and mass transfer properties. Solutions of reduced governing equations are obtained numerically via the shooting method and computed using the bvp-4c algorithm. The impacts of diverse active parameters such as porous medium, magnetic parameter, reciprocal magnetic Prandtl parameter, stretching parameter, HSS parameter, and relaxation time parameter for heat and mass flux are studied graphically. In addition, the values of significant engineering factors are calculated and comparative analysis is presented through bar graphs. It is seen that regular heat sink/source promotes thermal distribution and relaxation time for mass flux enhances the mass transfer rate between fluid flow and solid surface. [ABSTRACT FROM AUTHOR]

Abstract Microbubbles (MBs) combined with focused ultrasound (FUS) has emerged as a promising noninvasive technique to permeabilize the blood–brain barrier (BBB) for drug delivery into the brain. However, the safety and biological consequences of BBB opening (BBBO) remain incompletely understood. This study aims to investigate the effects of two parameters mediating BBBO: microbubble volume dose (MVD) and mechanical index (MI). High-resolution MRI-guided FUS was employed in mouse brains to assess BBBO by manipulating these two parameters. Afterward, the sterile inflammatory response (SIR) was studied 6 h post-FUS treatment. Results demonstrated that both MVD and MI significantly influenced the extent of BBBO, with higher MVD and MI leading to increased permeability. Moreover, RNA sequencing revealed upregulation of major inflammatory pathways and immune cell infiltration after BBBO, indicating the presence and extent of SIR. Gene set enrichment analysis identified 12 gene sets associated with inflammatory responses that were significantly upregulated at higher MVD or MI. A therapeutic window was established between therapeutically relevant BBBO and the onset of SIR, providing operating regimes to avoid damage from stimulation of the NFκB pathway via TNFɑ signaling to apoptosis. These results contribute to the optimization and standardization of BBB opening parameters for safe and effective drug delivery to the brain and further elucidate the underlying molecular mechanisms driving sterile inflammation.

[Display omitted] The goal of this study was to evaluate the performance of different commercial ultrasound contrast microbubbles (MBs) when measuring bladder phantom pressure with sub-harmonic-aided pressure estimation (SHAPE) methodology. We hypothesized that SHAPE performance is dependent on MB formulation. This study aimed to advance the SHAPE application for bladder pressure measurements in humans. Using a previously designed and built bladder phantom, we tested four different commercial agents: Definity, Lumason, Sonazoid and Optison. A standard clinical cystometrogram (CMG) system was used to infuse a MB–saline mixture into the bladder phantom to measure pressure. Ultrasound imaging was performed using the GE Healthcare LOGIQ E10 scanner. All agents showed a predicted inverse linear relationship between change in pressure and SHAPE signal. However, they differ from each other in terms of stability, linear correlation, sensitivity to pressure and error. Generally, Definity and Lumason showed the highest performance during the SHAPE-based bladder phantom pressure assessments. Our results show that the SHAPE signal decreases as bladder phantom pressures increases, regardless of the agent or CMG phase, suggesting the possibility of using SHAPE for measuring bladder pressure without a catheter. However, the efficacy of SHAPE in measuring pressure varies by MB formulation. These observations support using Lumason and Definity in a human subject feasibility study as we advance toward a catheter-free solution for measuring voiding bladder pressure via SHAPE. [ABSTRACT FROM AUTHOR]

Drug delivery to central nervous pathologies is compromised by the blood-brain barrier (BBB). A clinically explored strategy to promote drug delivery across the BBB is sonopermeation, which relies on the combined use of ultrasound (US) and microbubbles (MB) to induce temporally and spatially controlled opening of the BBB. We developed an advanced in vitro BBB model to study the impact of sonopermeation on the delivery of the prototypic polymeric drug carrier pHPMA as a larger molecule and the small molecule antiviral drug ribavirin. This was done under standard and under inflammatory conditions, employing both untargeted and RGD peptide-coated MB. The BBB model is based on human cerebral capillary endothelial cells and human placental pericytes, which are co-cultivated in transwell inserts and which present with proper transendothelial electrical resistance (TEER). Sonopermeation induced a significant decrease in TEER values and facilitated the trans-BBB delivery of fluorescently labeled pHPMA (Atto488-pHPMA). To study drug delivery under inflamed endothelial conditions, which are typical for e.g. tumors, neurodegenerative diseases and CNS infections, tumor necrosis factor (TNF) was employed to induce inflammation in the BBB model. RGD-coated MB bound to and permeabilized the inflamed endothelium-pericyte co-culture model, and potently improved Atto488-pHPMA and ribavirin delivery. Taken together, our work combines in vitro BBB bioengineering with MB-mediated drug delivery enhancement, thereby providing a framework for future studies on optimization of US-mediated drug delivery to the brain. [ABSTRACT FROM AUTHOR]

The first use of ultrasound in treating vascular disorders dates back to 1976. Since then, numerous original studies have been published, offering various concepts of its use. Many technical solutions have been developed and used with variable success, some of which have been developed in modern medicine. This article discusses the development of ultrasound therapeutic technologies in treating vascular disorders. The history of methods is described, available data on promising future areas are presented, and information on existing methods and devices is given.

Abstract Improving the efficacy of chemotherapy remains a key challenge in cancer treatment, considering the low bioavailability, high cytotoxicity, and undesirable side effects of some clinical drugs. Targeted delivery and sustained release of therapeutic drugs to cancer cells can reduce the whole-body cytotoxicity of the agent and deliver a safe localized treatment to the patient. There is growing interest in herbal drugs, such as curcumin, which is highly noted as a promising anti-tumor drug, considering its wide range of bioactivities and therapeutic properties against various tumors. Conversely, the clinical efficacy of curcumin is limited because of poor oral bioavailability, low water solubility, instability in gastrointestinal fluids, and unsuitable pH stability. Drug-delivery colloid vehicles like liposomes and nanoparticles combined with microbubbles and ultrasound-mediated sustained release are currently being explored as effective delivery modes in such cases. This study aimed to synthesize and study the properties of curcumin liposomes (CLs) and optimize the high-frequency ultrasound release and uptake by a human breast cancer cell line (HCC 1954) through in vitro studies of culture viability and cytotoxicity. CLs were effectively prepared with particles sized at 81 ± 2 nm, demonstrating stability and controlled release of curcumin under ultrasound exposure. In vitro studies using HCC1954 cells, the combination of CLs, ultrasound, and Definity microbubbles significantly improved curcumin’s anti-tumor effects, particularly under specific conditions: 15 s of continuous ultrasound at 0.12 W/cm2 power density with 0.6 × 107 microbubbles/mL. Furthermore, the study delved into curcumin liposomes’ cytotoxic effects using an Annexin V/PI-based apoptosis assay. The treatment with CLs, particularly in conjunction with ultrasound and microbubbles, amplified cell apoptosis, mainly in the late apoptosis stage, which was attributed to heightened cellular uptake within cancer cells.

Experiments on ultrasound propagation through a gel doped with resonant encapsulated microbubbles provided evidence for a discontinuous transition between wave propagation regimes at a critical excitation frequency. Such behavior is unlike that observed for soft materials doped with non-resonant air or through liquid foams, and disagrees with a simple mixture model for the effective sound speed. Here, we study the discontinuous transition by measuring the transition as a function of encapsulated microbubble volume fraction. The results show the transition always occurs in the strong-scattering limit (l/λ < 1, l and λ are the mean free path and wavelength, respectively), that at the critical frequency the effective phase velocity changes discontinuously to a constant value with increasing microbubble volume fraction, and the measured critical frequency shows a power law dependence on microbubble volume fraction. The results cannot be explained by multiple scattering theory, viscous effects, mode decoupling, or a critical density of states. It is hypothesized the transition depends upon the microbubble on-resonance effective properties, and we discuss the results within the context of percolation theory. The results shed light on the discontinuous transition's physics, and suggest soft materials can be engineered in this manner to achieve a broad range of physical properties with potential application in ultrasonic actuators and switches. [ABSTRACT FROM AUTHOR]

Gas bubbling can be an effective means to float out alumina inclusions from liquid steel in a ladle. However, large spherical cap bubbles are formed when using porous plugs, as the liquid steel is nonwetting to the porous refractory. These bubbles rise rapidly through the liquid steel, forming a fast‐moving bubble plume, restricting contact times. Sized microbubbles, by contrast, have now been generated in liquid metals by shearing methods, involving linear crossflows to an entering flow of gas, or alternatively by rotational shearing. Combined with these convective shearing forces, local kinetic energy of turbulence can also play an important part in determining final microbubble size distributions. As microbubbles have much smaller rise velocities and present a far greater inclusion capture surface area than those of a single large bubble of the same gross volume, this will allow us to remove sub‐50 μm inclusions from liquid steel. It is expected that this goal will require a redesign of current ladle shrouds. [ABSTRACT FROM AUTHOR]

Antibacterial sonothermal therapy (ASTT) is attractive for treating implant‐associated infection, which addresses the limitations of poor penetration of photothermal therapy. However, achieving implant surface‐specific ultrasound heating is incredibly challenging. Inspired by the porous acoustic metastructure in noise reduction, the acoustic metastructure would be a new strategy for attaining ASTT. Herein, an "acoustic confinement effect" is proposed to "trap" ultrasound for the metastructure TiO2 porous coating on titanium implants. The metastructure coating accomplishes specific acoustic absorption and efficient acoustic‐to‐thermal conversion, surpassing the non‐specific heating of conventional coatings. The theoretical calculation and experiment of metastructure porous coating prove the acoustic‐to‐thermal conversion mechanism, which is also validated in metastructure porous coatings on medical polyetheretherketone, indicating it is universal. Excitingly, this acoustic metastructure "trap" can capture bacteria and local sonothermal enhancement, exhibiting superior ASTT antibacterial rates (S. aureus, 99.69%; E. coil, 99.58%) at low‐power ultrasound. In addition, the metastructure TiO2 coating mimics human bone and demonstrates outstanding osseointegration. This study sheds substantial light on developing the acoustic responsive surface, broadening a new direction of acoustic metamaterials in medical applications. [ABSTRACT FROM AUTHOR]