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Introduction: Alzheimer's disease, a progressive neurodegenerative disorder, is marked by beta-amyloid plaque accumulation and cognitive decline. The limited efficacy and significant side effects of anti-amyloid monoclonal antibody therapies have prompted exploration into innovative treatments like focused ultrasound therapy. Focused ultrasound shows promise as a noninvasive technique for disrupting the blood-brain barrier, potentially enhancing drug delivery directly to the brain and improving the penetration of existing therapeutic agents. Methods: This systematic review was conducted using PubMed and Embase databases, focusing on studies published in the last ten years that examined the use of low-intensity focused ultrasound for blood-brain barrier disruption in Alzheimer's disease. The search strategy encompassed terms related to Alzheimer's disease, focused ultrasound, and the blood-brain barrier. Studies were selected based on predefined inclusion and exclusion criteria. The quality of included studies was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence framework. Results: Twelve studies were analyzed, the results of which suggested that low intensity focused ultrasound when combined with microbubbles may safely and transiently disrupt the blood-brain barrier. These studies, primarily early-phase and observational, highlight the potential feasibility of focused ultrasound in facilitating drug delivery to the brain for the treatment of Alzheimer's disease. Notably, one study reported positive impacts on cognitive tests, suggesting potential direct therapeutic effects of focused ultrasound beyond blood-brain barrier disruption. Conclusion: The results of the included studies indicate the use of focused ultrasound in Alzheimer's disease treatment might be safe and effective in transiently opening the blood-brain barrier. Although current evidence is promising, further research is needed to establish generalizability. Future studies should also aim to further elucidate the mechanisms of action of low-intensity focused ultrasound as well as microbubbles for blood-brain barrier opening and explore potential clinical benefits beyond blood-brain barrier opening such as impacts on cognitive outcomes. Future studies should also aim for greater participant diversity to ensure findings are applicable across the full spectrum of Alzheimer's disease patients. [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]

Simple Summary: Boron neutron capture therapy (BNCT) is radiotherapy that depends on a nuclear reaction between boron-10 (10B) and neutrons. The neutron source has been changing from nuclear reactors to accelerators. Current BNCT using boronophenylalanine (BPA) as the boron compound has been shown to markedly reduce tumor sizes when used to treat recurrent head and neck cancer (HNC); however, early recurrence has been reported. Ultrasound, a safe diagnostic method, in combination with microbubbles, is expected to promote the uptake of BPA into tumor cells. Ultrasound also has the ability to increase the sensitivity of cancer cells to radiotherapy. Therefore, the combination of ultrasound needs to be promoted in order to improve the antitumor efficacy of BNCT for HNC. Boron neutron capture therapy (BNCT) is radiotherapy in which a nuclear reaction between boron-10 (10B) in tumor cells and neutrons produces alpha particles and recoiling 7Li nuclei with an extremely short range, leading to the destruction of the tumor cells. Although the neutron source has traditionally been a nuclear reactor, accelerators to generate neutron beams have been developed and commercialized. Therefore, this treatment will become more widespread. Recurrent head and neck cancer (HNC) close to the body surface is considered a candidate for BNCT using the boron compound boronophenylalanine (BPA) and has been found to be highly responsive to this treatment. However, some cases recur early after the completion of the treatment, which needs to be addressed. Ultrasound is a highly safe diagnostic method. Ultrasound with microbubbles is expected to promote the uptake of BPA into tumor cells. Ultrasound also has the ability to improve the sensitivity of tumor cells to radiotherapy. In addition, high-intensity focused ultrasound may improve the efficacy of BNCT via its thermal and mechanical effects. This review is not systematic but outlines the current status of BPA-based BNCT and proposes plans to reduce the recurrence rate of HNC after BNCT in combination with ultrasound. [ABSTRACT FROM AUTHOR]

Objective: Evaluation of tumor microvascular morphology is of great significance in tumor diagnosis, therapeutic effect prediction, and surgical planning. Recently, two-dimensional ultrasound localization microscopy (2DULM) has demonstrated its superiority in the field of microvascular imaging. However, it suffers from planar dependence and is unintuitive. We propose a novel three-dimensional ultrasound localization microscopy (3DULM) to avoid these limitations. Methods: We investigated 3DULM based on a 2D array for tumor microvascular imaging. After intravenous injection of contrast agents, all elements of the 2D array transmit and receive signals to ensure a high and stable frame rate. Microbubble signal extraction, filtering, positioning, tracking, and other processing were used to obtain a 3D vascular map, flow velocity, and flow direction. To verify the effectiveness of 3DULM, it was validated on double helix tubes and rabbit VX2 tumors. Cisplatin was used to verify the ability of 3DULM to detect microvascular changes during tumor treatment. Results: In vitro, the sizes measured by 3DULM at 3 mm and 13 mm were 178 μ m and 182 μ m , respectively. In the rabbit tumors, we acquired 9000 volumes to reveal vessels about 30 μ m in diameter, which surpasses the diffraction limit of ultrasound in traditional ultrasound imaging, and the results matched with micro-angiography. In addition, there were significant changes in vascular density and curvature between the treatment and control groups. Conclusions: The effectiveness of 3DULM was verified in vitro and in vivo. Hence, 3DULM may have potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease. Clinical relevance statement: 3D ultrasound localization microscopy is highly sensitive to microvascular changes; thus, it has clinical potential for tumor diagnosis and treatment evaluation. Key Points: • 3D ultrasound localization microscopy is demonstrated on double helix tubes and rabbit VX2 tumors. • 3D ultrasound localization microscopy can reveal vessels about 30 μ m in diameter—far smaller than traditional ultrasound. • This form of imaging has potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease. [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]

Abstract Background Acute thrombotic events play a major role in various cardiovascular diseases. Therefore, direct thrombus imaging can be proved beneficial for early diagnosis and prompt therapy of thrombosis. Our study investigated targeted dual‐modality cyclic arginine‐glycine‐aspartic micro bubbles (cRGD‐MBs) for direct imaging of thrombi by fluorescence and ultrasound. Methods cRGD‐MBs were prepared by mechanical vibration and chemical chelation methods. Results Coulter counter analysis demonstrated that the cRGD‐MBs were well dispersed, with diameters ranging from 1 to 3 μm. They emitted bright red fluorescence under an excitation wavelength of 660 nm. In vivo fluorescence and ultrasound imaging revealed that cRGD‐MBs accumulated at the site of thrombus in the carotid artery with significant fluorescence and ultrasonic signal. Conclusions This study showed that novel microbubble cRGD‐MBs were successfully synthesized, and that these could potentially be used as contrast agents for immediate diagnosis of acute thrombus in vivo.

Background and Objectives: Microbubbles (MBs) are gas or vapor-filled cavities inside liquids with sizes ranging from 2 to 3 µm. Recently, MBs have shown great promise in nanomedicine owing to their high encapsulation efficiency, targeted drug release, improved biocompatibility, and longer blood circulation. Furthermore, they are more suitable for focusing on particular body regions and are safer and non-invasive. MBs generators are used to create bubbles in fluid dynamics, chemistry, medicine, agriculture, and the environment. Drug delivery using MBs increases penetration without causing systemic toxicity. In this study, we examined whether the use of microbubbles as a local drug-delivery mechanism increases tubular penetration of endodontic medications and irrigant. Materials and Methods: An Enterococcus faecalis culture was added to 38 dentin cylinders of single-rooted teeth. Samples were divided into the experimental and control groups that received a triple antibiotic paste with and without MB infusion (n = 19 in each group), respectively. After 14 days, the number of live bacteria in the samples was determined using confocal laser scanning microscopy. Results: After 14 days of contact with the medication, the percentages of live and dead bacteria were assessed. Results show that Group 2 (Triple antibiotic infused micro bubble) showed significantly (P

Among several separation processes, air flotation is distinguished as a remarkably high potential separation process related to its high separation efficiency and throughput, energy-efficient, simple process, cost-effective, applicability to a wide range of oily wastewater, and no by-products. The current study aimed to investigate the effect of the type and concentration of surfactant on the stability of oil-water emulsion and the efficiency of the separation process. For this purpose, three types of surfactant were used (anionic SDS, mixed nonionic Span 85/Tween 80, and cationic CTAB). The results demonstrated that the Span 85/Tween 80 surfactant has the best stability, and it increases with the surfactant concentration augmentation. The removal efficiency with CTAB surfactant reached approximately 95% at a concentration of 0.3% and decreased by increasing the surfactant concentration. The mean diameter of bubbles generated in the emulsion with CTAB surfactant was 71 µm, which was lower than that obtained with the other two surfactants.

The low energy consumption and efficient treatment of oily wastewater using microbubble flotation technology is a current research hotspot. A low-energy microbubble jet flotation system for treating oily wastewater was established using an effervescent atomizer as a microbubble generator. The effects of air-liquid mass flow ratio(ALR) and working pressure (p) on the size distribution characteristics of microbubbles and de-oiling capacity were discussed, and the energy consumption of effervescent atomizer was analyzed. The experimental results showed that a large number of microbubbles could be generated by using the effervescent atomizer to organize submerged jet, the number of microbubbles with diameters less than 150 μm accounted for more than 55%, and the number of microbubbles with diameters less than 600 μm accounted for more than 98%. The number of microbubbles increased first and then decreased with the increase of ALR, and the optimum ALR was 0.15. When p was 0.2 MPa and ALR was 0.15, the Sauter mean diameter of microbubbles could be as low as 238 μm, the oil concentration in wastewater was 29.73 mg/L, the power consumed by the microbubble jet flotation was only 6.53×10-4 kW·h per kilogram of wastewater , which was more than 35% lower than dissolved air flotation.

Abstract While numerous types of chemical cosmetic cleansers have been presented, those with sensitive skin may still experience some irritation while using them. Moreover, the environmental issue of chemical agents has been documented repeatedly. To address these, we suggest the potential application of a micro-sized bubble-laden water jet to cleanse the cosmetics without (or less) using chemical detergents. We devised a venturi-type nozzle with a mesh and air holes capable of generating massive fine bubbles. By testing with the foundation and lip tint (known to be highly adhesive) coated on the synthetic leather and artificial skin surfaces, we measured that the cleansing performance of the bubbly jet is much better (even without the chemical agent) than the single-phase liquid jet. As a mechanism for enhanced removal, it is understood that the greater kinetic energy of the jet due to the acceleration of the effective liquid–air mixture flow and the direct bubble-cosmetic collisions play essential roles. We believe that the present results will spur the development of environment-friendly cleaning methods.

We believe our poly(lactic acid) (PLA) microbubbles are well suited for therapeutic delivery to spinal cord injury (SCI) using ultrasound-triggered bursting. We investigated the feasibility of clinical ultrasound bursting in situ , the optimal bursting parameters in vitro and the loading and release of a model bio-active DNA. Microbubbles were tested using clinical ultrasound in a rat cadaver SCI model. Burst pressure thresholds were determined using the change in enhancement after ultrasound exposure. Resonance frequency, acoustic enhancement, sizing and morphology were evaluated by comparing two microbubble porogens, ammonium carbonate and ammonium carbamate. Oligonucleotides were loaded into the shell and released using the found optimized ultrasound bursting parameters. In situ imaging and bursting were successful. In vitro bursting thresholds using frequencies 1, 2.25 and 5 MHz were identified between peak negative pressures 0.2 and 0.5 MPa, believed to be safe for spinal cord. The pressure threshold decreased with decreasing frequencies. PLA bursting was optimized near the resonance frequency of 2.5 to 3.0 MHz using 2.25 MHz and not at lower frequencies. PLA microbubbles, initially with a mean size of approximately 2 µm, remained in one piece, collapsed to between 0.5 and 1 µm and did not fragment. Significantly more oligonucleotide was released after ultrasound bursting of loaded microbubbles. Microbubble-sized debris was detected when using ammonium carbamate, leading to inaccurate microbubble concentration measurements. PLA microbubbles made with ammonium carbonate and burst at appropriate parameters have the potential to safely improve intrathecal therapeutic delivery to SCI using targeted ultrasound. [ABSTRACT FROM AUTHOR]

Microbubbles (MBs) are gas or vapor-filled cavities inside liquids with sizes ranging from 2 to 3 µm. Recently, MBs have shown great promise in nanomedicine owing to their high encapsulation efficiency, targeted drug release, improved biocompatibility, and longer blood circulation. Furthermore, they are more suitable for focusing on particular body regions and are safer and non-invasive. MBs generators are used to create bubbles in fluid dynamics, chemistry, medicine, agriculture, and the environment. Drug delivery using MBs increases penetration without causing systemic toxicity. In this study, we examined whether the use of microbubbles as a local drug-delivery mechanism increases tubular penetration of endodontic medications and irrigant. An Enterococcus faecalis culture was added to 38 dentin cylinders of single-rooted teeth. Samples were divided into the experimental and control groups that received a triple antibiotic paste with and without MB infusion (n = 19 in each group), respectively. After 14 days, the number of live bacteria in the samples was determined using confocal laser scanning microscopy. After 14 days of contact with the medication, the percentages of live and dead bacteria were assessed. Results show that Group 2 (Triple antibiotic infused micro bubble) showed significantly (P < 0.05) higher antibacterial efficacy than Group 1 (TAP). In this study, the antibacterial efficacy was significantly higher in the experimental group than in the control group. Therefore, within the limitations of the study it can be said that MB infusion is a viable technique to improve root canal disinfection. Hence, it can be considered as a novel technique for local drug delivery systems in endodontic management. [ABSTRACT FROM AUTHOR]

This work reports a simple bubble generator for the high-speed generation of microbubbles with constant cumulative production. To achieve this, a gas–liquid co-flowing microfluidic device with a tiny capillary orifice as small as 5 μm is fabricated to produce monodisperse microbubbles. The diameter of the microbubbles can be adjusted precisely by tuning the input gas pressure and flow rate of the continuous liquid phase. The co-flowing structure ensures the uniformity of the generated microbubbles, and the surfactant in the liquid phase prevents coalescence of the collected microbubbles. The diameter coefficient of variation (CV) of the generated microbubbles can reach a minimum of 1.3%. Additionally, the relationship between microbubble diameter and the gas channel orifice is studied using the low Capillary number (Ca) and Weber number (We) of the liquid phase. Moreover, by maintaining a consistent gas input pressure, the CV of the cumulative microbubble volume can reach 3.6% regardless of the flow rate of the liquid phase. This method not only facilitates the generation of microbubbles with morphologic stability under variable flow conditions, but also ensures that the cumulative microbubble production over a certain period of time remains constant, which is important for the volume-dominated application of chromatographic analysis and the component analysis of natural gas. [ABSTRACT FROM AUTHOR]

Among several separation processes, the air flotation distinguish as remarkably high potential separation process related to its high separation efficiency and throughput, energy-efficient, simple process, cost-effective, applicable to a wide range of oily wastewater and no by-products. The current study aimed to investigate the effect of the type and concentration of surfactant on the stability of oil-water emulsion and efficiency of the separation process. For this purpose, three types of surfactant where used (anionic SDS, mixed nonionic Span 85/Tween 80, and cationic CTAB). The results demonstrated that the Span 85/Tween 80 surfactant has the best stability, and it increases with the surfactant concentration augmentation. The removal efficiency with CTAB surfactant reached to approximately 95% at concentration of 0.3%, and decreased by increasing the surfactant concentration. The mean diameter of bubbles generated in emulsion with CTAB surfactant was 71 µm, which was lower than that obtained with the other two surfactants. [ABSTRACT FROM AUTHOR]

Microbubble shows great potential for hydrogenation reaction in fixed bed reactors (FBRs). However, the lack of understanding of the hydrodynamic behaviors of microbubble swarm in FBR limits the reactor design. In this work, a pilot‐scale HiGee‐aided fixed bed reactor (HFBR), including a HiGee microbubble generator (HMG) and a catalyst bed, has been developed and then applied for poly alpha olefin 4 (PAO 4) hydrogenation. An empirical correlation of Sauter mean diameter (d32) of microbubbles at the inlet and outlet of catalyst bed was established. The gas holdup (φb) of catalyst bed with HMG was 5–10 times higher than that without HMG. Based on d32 and φb, the effective interfacial area in HFBR was calculated as 2000–6000 m2/m3. Compared with static mixer‐aided fixed bed reactor, the aromatic content of PAO 4 hydrogenated in the HFBR was 56%–69% lower, which shows bright future for industrial application. [ABSTRACT FROM AUTHOR]

Spherical micro/nanorobots are reported as attractive candidates in nano‐surgery, contamination degradation, analytical chemistry, medical engineering, etc. Unlike macroscopic robots, the standard fabrication and inspection strategy to control the high quality of microrobots are rarely explored before. Overcoming the geometrical discrepancy is now essential to keep an identical locomotion behavior for spherical microrobot individuals for complex usages. Herein, acoustic‐based microbubble grippers are proposed controlled by a machine vision system to realize agile recognition and sorting of unqualified spherical microrobot models. Theoretical analysis and numerical simulation reveal the basic grabbing mechanisms via acoustic stimuli. The acoustic resonation of microbubbles can generate a locally enhanced acoustic field, attracting microrobots toward the bubble surface by the acoustic forces. The viscosity of microfluid makes it possible to instantaneously grab or release just by controlling the microbubble activation. Further, a machine vision‐based monitor and control system is proposed to enable automatic control for the entire process. Based on extracted characteristic parameters, target microrobot models are quickly selected and grabbed out. It is expected that such a combination of microgrippers with an advanced control system will pave the way for high‐qualified inspection for microrobots and improve their unique versatility in myriad micromanipulation scenarios. [ABSTRACT FROM AUTHOR]

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Carbon monoxide is a gasotransmitter that may be beneficial for vascular tissue engineering and regenerative medicine strategies because it can promote endothelial cell (EC) proliferation and migration by binding to heme‐containing compounds within cells. For example, CO may be beneficial for vascular cognitive impairment and dementia because many patients' disrupted blood–brain barriers do not heal naturally. However, control of the CO dose is critical, and new controlled delivery methods need to be developed. This study developed ultrasound‐sensitive microbubbles with a carefully controlled precipitation technique, loaded them with CO, and assessed their ability to promote EC proliferation and function. Microbubbles fabricated with perfluoropentane exhibited good stability at room temperature, but they could still be ruptured and release CO in culture with application of ultrasound. Microbubbles synthesized from the higher boiling point compound, perfluorohexane, were too stable at physiological temperature. The lower‐boiling point perfluoropentane microbubbles had good biocompatibility and appeared to improve VE‐cadherin expression when CO was loaded in the bubbles. Finally, tissue phantoms were used to show that an imaging ultrasound probe can efficiently rupture the microbubbles and that the CO‐loaded microbubbles can improve EC spreading and proliferation compared to control conditions without microbubbles as well as microbubbles without application of ultrasound. Overall, this study demonstrated the potential for use of these ultrasound‐sensitive microbubbles for improving blood vessel endothelialization. [ABSTRACT FROM AUTHOR]

This study aimed to compare the plasma-activated water (PAW) and plasma-activated microbubble water (PAMBW) with commercial sodium hypochlorite (SH) for postharvest processing of fresh-cut romaine lettuce. The PAW and PAMBW properties showed that PAMBW produced higher content and more effective reactive oxygen and nitrogen species than PAW. PAMBW treatment recorded a 4.6 log10 CFU/g Escherichia coli (E. coli) O157:H7 reduction on lettuce compared to a 3.2 log10 CFU/g reduction by SH. Field emission scanning electron microscopy (FE-SEM) and qRT-PCR revealed that the reactive species generated by PAMBW treatment damaged the E. coli O157:H7 cell membranes and significantly (P

IntroductionAlzheimer’s disease, a progressive neurodegenerative disorder, is marked by beta-amyloid plaque accumulation and cognitive decline. The limited efficacy and significant side effects of anti-amyloid monoclonal antibody therapies have prompted exploration into innovative treatments like focused ultrasound therapy. Focused ultrasound shows promise as a non-invasive technique for disrupting the blood–brain barrier, potentially enhancing drug delivery directly to the brain and improving the penetration of existing therapeutic agents.MethodsThis systematic review was conducted using PubMed and Embase databases, focusing on studies published in the last ten years that examined the use of low–intensity focused ultrasound for blood–brain barrier disruption in Alzheimer’s disease. The search strategy encompassed terms related to Alzheimer’s disease, focused ultrasound, and the blood–brain barrier. Studies were selected based on predefined inclusion and exclusion criteria. The quality of included studies was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence framework.ResultsTwelve studies were analyzed, the results of which suggested that low intensity focused ultrasound when combined with microbubbles may safely and transiently disrupt the blood–brain barrier. These studies, primarily early-phase and observational, highlight the potential feasibility of focused ultrasound in facilitating drug delivery to the brain for the treatment of Alzheimer’s disease. Notably, one study reported positive impacts on cognitive tests, suggesting potential direct therapeutic effects of focused ultrasound beyond blood–brain barrier disruption.ConclusionThe results of the included studies indicate the use of focused ultrasound in Alzheimer’s disease treatment might be safe and effective in transiently opening the blood–brain barrier. Although current evidence is promising, further research is needed to establish generalizability. Future studies should also aim to further elucidate the mechanisms of action of low-intensity focused ultrasound as well as microbubbles for blood–brain barrier opening and explore potential clinical benefits beyond blood–brain barrier opening such as impacts on cognitive outcomes. Future studies should also aim for greater participant diversity to ensure findings are applicable across the full spectrum of Alzheimer’s disease patients.

Sonoporation is a non-invasive method that uses ultrasound for drug and gene delivery for therapeutic purposes. Here, both Finite Element Method (FEM) and Lattice Boltzmann Method (LBM) are applied to study the interaction physics of microbubble oscillation and collapse near flexible tissue. After validating the Finite Element Method with the nonlinear excited lipid-coated microbubble as well as the Lattice Boltzmann Method with experimental results, we have studied the behavior of a three-dimensional compressible microbubble in the vicinity of tissue. In the FEM phase, the oscillation microbubble with a lipid shell interacts with the boundary. The range of pressure and ultrasound frequency have been considered in the field of therapeutic applications of sonoporation. The viscoelastic and interfacial tension as the coating properties of the microbubble shell have been investigated. The presence of an elastic boundary increases the resonance frequency of the microbubble compared to that of a free microbubble. The increase in pressure leads to an expansion in the range of the microbubble’s motion, the velocity induced in the fluid, and the shear stress on the boundary walls of tissue. An enhancement in the surface tension of the microbubble can influence fluid flow and reduce the shear stress on the boundary. The multi-pseudo-potential interaction LBM is used to reduce thermodynamic inconsistency and high-density ratio in a two-phase system for modeling the cavitation process. The three-dimensional shape of the microbubble during the collapse stages and the counter of pressure are displayed. There is a time difference between the occurrence of maximum velocity and pressure. All results in detail are presented in the article bodies.

Recently, our group developed a synergistic brain drug delivery method to achieve simultaneous transcranial hyperthermia and localized blood–brain barrier opening via MR-guided focused ultrasound (MRgFUS). In a rodent model, we demonstrated that the ultrasound power required for transcranial MRgFUS hyperthermia was significantly reduced by injecting microbubbles (MBs). However, the specific mechanisms underlying the power reduction caused by MBs remain unclear. The present study aims to elucidate the mechanisms of MB-enhanced transcranial MRgFUS hyperthermia through numerical studies using the finite element method. The microbubble acoustic emission (MAE) and the viscous dissipation (VD) were hypothesized to be the specific mechanisms. Acoustic wave propagation was used to model the FUS propagation in the brain tissue, and a bubble dynamics equation for describing the dynamics of MBs with small shell thickness was used to model the MB oscillation under FUS exposures. A modified bioheat transfer equation was used to model the temperature in the rodent brain with different heat sources. A theoretical model was used to estimate the bubble shell’s surface tension, elasticity, and viscosity losses. The simulation reveals that MAE and VD caused a 40.5% and 52.3% additional temperature rise, respectively. Compared with FUS only, MBs caused a 64.0% temperature increase, which is consistent with our previous animal experiments. Our investigation showed that MAE and VD are the main mechanisms of MB-enhanced transcranial MRgFUS hyperthermia.

In up to 30% patients who experience acute myocardial infarction, successful recanalization of the epicardial coronary artery cannot provide adequate microvascular reperfusion. In this study, we sought to determine whether long-pulsed ultrasound (US)-mediated microbubble (MB) cavitation was useful for the treatment of microvascular obstruction, and the therapeutic effects were compared within different long-pulse-length and short-pulsed US. Microvascular obstruction model was established by injecting micro-thrombi into common iliac artery of a rat’s hind limb. About 1 MHz US with different long pulse lengths (ranging from 100 to 50,000 cycles) was delivered, compared to short pulse (5 cycles). The control group was given MB only without therapeutic US. Contrast perfusion images were performed at baseline, emboli, and 1, 5, 10 min post-embolization, and peak plateau video intensity (A) was obtained to evaluate the therapeutic effects. Long-tone-burst US showed better thrombolytic effects than short-pulsed US (1,000, 5,000 cycles >500 cycles, >5 cycles, and control) (P < 0.01). 1,000 cycles group showed the optimal thrombolytic effect, but microvascular hemorrhage was observed in 50,000 cycles group. In conclusion, long-tone-burst US-enhanced MB therapy mediated successful thrombolysis and may offer a powerful approach for the treatment for microvascular obstruction within a certain pulse length.

Ultrasound-targeted microbubble cavitation (UTMC)-mediated blood–brain barrier (BBB) opening is being explored as a method to increase drug delivery to the brain. This strategy has progressed to clinical trials for various neurological disorders, but the underlying cellular mechanisms are incompletely understood. In the study described here, a contact co-culture transwell model of the BBB was developed that can be used to determine the signaling cascade leading to increased BBB permeability. This BBB model consists of bEnd.3 cells and C8-D1A astrocytes seeded on opposite sides of a transwell membrane. Pulsed ultrasound (US) is applied to lipid microbubbles (MBs), and the change in barrier permeability is measured via transendothelial electrical resistance and dextran flux. Live cell calcium imaging (Fluo-4 AM) is performed during UTMC treatment. This model exhibits important features of the BBB, including endothelial tight junctions, and is more restrictive than the endothelial cell (EC) monolayer alone. When US is applied to MBs in contact with the ECs, BBB permeability increases in this model by two mechanisms: UTMC induces pore formation in the EC membrane (sonoporation), leading to increased transcellular permeability, and UTMC causes formation of reversible inter-endothelial gaps, which increases paracellular permeability. Additionally, this study determines that calcium influx into ECs mediates the increase in BBB permeability after UTMC in this model. Both transcellular and paracellular permeability can be used to increase drug delivery to the brain. Future studies can use this model to determine how UTMC-induced calcium-mediated signaling increases BBB permeability. [ABSTRACT FROM AUTHOR]

In this study, we investigated the detachment of an oil droplet from a wall surface by microbubbles (MBs) using the numerical simulation of a gas–liquid–liquid three‐phase flow based on a phase‐field model. A single MB was collided with an oil droplet adhered to a wall surface to determine whether the droplet would detach from the wall. It was confirmed that the oil droplet detached from the wall when the interfacial tension between the water and oil or between the bubble and oil was low. To clarify the mechanism, we theoretically calculated the balance of interfacial tension at the three‐fluid contact line. The lower the interfacial tension between the water and oil and between the bubble and oil, the smaller the contact angle of the oil droplet on the bubble. This increased wettability was the driving force that caused the oil droplet to detach from the wall surface. [ABSTRACT FROM AUTHOR]

Accurate visualization of bubbles in multiphase flow is a crucial aspect of modeling heat transfer, mixing, and turbulence processes. It has many applications, including chemical processes, wastewater treatment, and aquaculture. A new software, Flow_Vis, based on experimental data visualization, has been developed to visualize the movement and size distribution of bubbles within multiphase flow. Images and videos recorded from an experimental rig designed to generate microbubbles were analyzed using the new software. The bubbles in the fluid were examined and found to move with different velocities due to their varying sizes. The software was used to measure bubble size distributions, and the obtained results were compared with experimental measurements, showing reasonable accuracy. The velocity measurements were also compared with literature values and found to be equally accurate. [ABSTRACT FROM AUTHOR]

Increasing evidence has suggested a link between cerebrovascular disease and the cognitive impairment associated with Alzheimer's disease. However, detailed descriptions of microvascular changes across brain regions and how they relate to other more traditional pathology have been lacking. Additionally, the efforts to elucidate the interplay between cerebral microvascular function and Alzheimer's disease progression are complicated by the necessity of probing deep-brain structures since early-stage Alzheimer's disease typically involves hippocampal pathology. The purpose of this study was to examine changes in microvascular dynamics in a mouse model of Alzheimer's disease using cohorts that were age-matched to wild-type controls. Data from both sexes were included in this study. Super-resolution ultrasound localization microscopy revealed microvascular functional and structural features throughout the whole brain depth to visualize and quantify. We found that functional decreases in hippocampal and entorhinal flow velocity preceded structural derangements in regional vascular density. Co-registered histological sectioning confirmed the regionalized perfusion deficits seen on ultrasound imaging, which were co-localized with amyloid beta plaque deposition. In addition to providing global vascular quantifications of deep brain structures with a high local resolution, this technology also permitted velocity-profile analysis of individual vessels and, in some cases, allowed for decoupling of arterial and venous flow contributions. These data suggest that microvascular pathology is an early and pervasive feature of Alzheimer's disease and may represent a novel therapeutic target for this disease. [ABSTRACT FROM AUTHOR]

Fast increased amount of excess activated sludge (EAS) from wastewater treatment plants has aroused universal concerns on its environmental risks and demands for appropriate treatments, while effective treatment is dependent upon proper pretreatment. In this study, air-supplied microbubbles (air-MBs) with generated size of 25.18 to 28.25 μm were used for EAS pretreatment. Different durations (30, 60, 90, and 120 s) yielded sludge with varied physiochemical conditions, and 60 s decreased sludge oxidation status and significantly increased adenosine triphosphate (ATP) content. Soluble, loosely-bound, and tightly-bound extracellular polymeric substances (SEPS, LB-EPS, and TB-EPS) were extracted from the sludge through a stepwise approach and examined through three-dimensional excitation-emission matrix (3D-EEM) and quantitative analysis. The results showed that 60- and 120-s treatments generated stronger fluorescence intensities on dissolved organic matters (DOMs) of protein-like and fulvic acid in LB-EPS and TB-EPS, which indicated the decrease of counterparts in EAS, and therefore facilitated sludge dewaterability and reduction. The dominant microbial communities in EAS, including Proteobacteria, Bacteroidota, Chloroflexi, and Actinobacteriota, were not significantly affected by MB pretreatment. The results collectively revealed the effects of MB pretreatment on EAS and indicated that MBs could be an effective pretreatment technique for EAS treatment process. [ABSTRACT FROM AUTHOR]

This paper investigated the aeration performance of micro-nanobubbles (MNBs) generated by using the ultrasonic micro-nanobubble preparation technology and the conventional aeration with large air bubbles.Experimental tests demonstrated that MNBs exhibit significantly enhanced stability and persistence compared to conventional aeration.The oxygen mass transfer coefficient of MNBs was 4.11 times that of conventional aeration, and their oxygen utilization efficiency was 3.30 times higher than that of conventional aeration.Comparative analysis highlighted the superiority of micro-nanobubble aeration over conventional aeration in terms of oxygen mass transfer efficiency and oxygen utilization rate.Under the same aeration intensity, MNBs rapidly elevated the dissolved oxygen (DO) concentration in the water, demonstrating their superior oxygen retention capability. After 24 hours of aeration cessation, the DO concentration in water treated with MNBs returned to its initial state, measuring 5.77 mg·L-1,whereas the DO concentration in the water tank aerated with conventional bubbles decreased to 5.82 mg·L-1 after just 1 hour of aeration cessation.Conventional aeration was widely used in environmental water treatment.The insights gained from this study regarding the performance differences of micro-nanobubble aeration are expected to provide theoretical and technological support for improving the effectiveness of water environmental treatment. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the appropriate combination of pulse length (PL) and pulse repetition frequency (PRF) when performing ultrasound stimulated microbubble (USMB) to enhance doxorubicin (DOX) delivery to tumors. Methods: A total of 48 tumor‐bearing mice were divided into four groups, namely groups A–D. The mice in groups B–D were treated with chemotherapy and USMB treatment with different combinations of PL and PRF, and group A was control. Contrast‐enhanced ultrasound imaging was conducted to analyze tumor blood perfusion. Fluorescence microscopy and high‐performance liquid chromatography were used to qualitatively and quantitatively analyse DOX release. The structural changes of tumors were observed under light microscope and transmission electron microscope. Furthermore, another 24 tumor‐bearing mice were treated with sonochemotherapy and some related inflammatory factors were measured to explore the underlying mechanism. Results: With PL of three cycles and PRF of 2 kHz, the tumor perfusion area ratio increased by 26.67%, and the DOX concentration was 4.69 times higher than the control (P <.001). With PL of 34.5 cycles and PRF of 200 Hz, the tumor perfusion area ratio decreased by 12.7% and DOX did not exhibit increased extravasation compared with the control. Microvascular rupture and hemorrhage were observed after long PL and low PRF treatment. While vasodilation and higher levels of some vasodilator inflammatory factors were found after treatment with short PL and high PRF. Conclusions: USMB treatment using short PL and high PRF could enhance tumor blood perfusion and increase DOX delivery, whereas long PL and low PRF could not serve the same purpose. [ABSTRACT FROM AUTHOR]

High-intensity focused ultrasound (HIFU) is a novel minimally invasive local treatment of solid tumors. Endoscopic ultrasound-guided HIFU (EUS-HIFU) using mechanical effects would have potential benefits, including precise detection of target lesions and enhance drug delivery. The aim of this study is to develop EUS-HIFU device and to prove our concept in porcine model using a locally injected phase change nano droplet (PCND) as the sensitizer. A phospholipid PCND contained volatile perfluoro-carbon liquids. The prototype HIFU apparatus comprised a small (20 × 20 mm) transducer with center frequency of 2.1 MHz, attachable to a linear EUS transducer. Under general anesthetic, a single porcine received EUS-guided injection of PCND. The HIFU transducer was placed laparotomically in the stomach, and the liver was ablated through the gastric wall. PCND was injected successfully and a distinct lesion was generated at the HIFU transducer focus only in injected areas that received HIFU exposure at 4.7 kW/cm2 at a duty cycle of 5 % (mean temporal intensity, 0.245 kW/cm2) for 30 s. The generated lesions were mechanically fractionated in macroscopic view. The concept of transluminal HIFU ablation using novel EUS-HIFU system was proved in a porcine animal model. This novel treatment system has great potential for future cancer treatment although further investigation in more animals and different organs are warranted. [ABSTRACT FROM AUTHOR]

[Display omitted] Microfluidics has recently been proposed as a viable method for producing bulk nanobubbles for use in various applications. The portability, compact size, and capacity to precisely control fluids on a small scale are a few of the benefits of microfluidics that may be exploited to create customized bulk nanobubbles. However, despite the potential of microfluidic nanobubble generation, low throughput and limited nanobubble concentration remain challenging for microfluidics. Here, we integrate a microporous silicon membrane into a polydimethylsiloxane microfluidic chip to generate bulk nanobubbles in the 100–140 nm diameter range with a concentration of up to 108 mL−1. We investigate the nanobubble size and morphology using several characterisation techniques, including transmission electron microscopy, resonance mass measurement, dynamic light scattering, and the Tyndall effect. This new nanobubble generation technique can increase nanobubble concentration by ∼ 23 times compared to earlier microfluidic nanobubble generation platforms, which should increase the feasibility of translation to medical applications. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) is an emerging antibacterial therapy. This work selected hematoporphyrin monomethyl ether (HMME) as the sonosensitizer, and studied the enhanced inhibition effect of Escherichia coli and biofilm by microbubble-mediated cavitation in SDT. Firstly, the influence of microbubble-mediated cavitation effect on different concentrations of HMME (10 µg/ml, 30 µg/ml, 50 µg/ml) was studied. Using 1,3-diphenylisobenzofuran (DPBF) as an indicator, the effect of microbubble-mediated cavitation on the production of reactive oxygen species (ROS) was studied by absorption spectroscopy. Secondly, using agar medium, laser confocal microscopy and scanning electron microscopy, the effect of microbubble-mediated cavitation on the activity and morphology of bacteria was studied. Finally, the inhibitory effect of cavitation combined with SDT on biofilm was evaluated by laser confocal microscopy. The research results indicate that: (1) Microbubble-mediated ultrasound cavitation can significantly increase cavitation intensity and production of ROS. (2) Microbubble-mediated acoustic cavitation can alter the morphological structure of bacteria. (3) It can significantly enhance the inhibition of SDT on the activity of Escherichia coli and its biofilm. Compared with the control group, the addition of microbubbles resulted in an increase in the number of dead bacteria by 61.7 %, 71.6 %, and 76.2 %, respectively. The fluorescence intensity of the biofilm decreased by 27.1 %, 80.3 %, and 98.2 %, respectively. On the basis of adding microbubbles to ensure antibacterial and biofilm inhibition effects, this work studied the influence of cavitation effect in SDT on bacterial structure, providing a foundation for further revealing the intrinsic mechanism of SDT.

Ultrasound is a widely used diagnostic medical imaging modality, and its therapeutic potential has recently been reported. This study examined whether ultrasound irradiation causes nanobubble destruction and identified the most effective frequency and duration of ultrasound for doxorubicin delivery in rat liver under ultrasound-targeted nanobubble destruction. Rats underwent an intravenous nanobubble injection via the caudal vein. An ultrasound probe was applied to the rat liver. The rats were divided into different groups based on the frequency. Fluorescence images were acquired using an IVIS® system. Laboratory tests were performed to determine the serum levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), total bilirubin, and creatinine. Under ultrasound irradiation, more nanobubbles were destroyed, and the doxorubicin uptake was increased in the rat liver (P ＜ 0.05). The 5 MHz group showed an increased fluorescence efficiency in the liver (P ＜ 0.05). Based on the duration of ultrasound irradiation, the 5, 10, and 13 MHz groups showed an increased fluorescence efficiency in the liver compared to the control group (P ＜ 0.05). There was no significant difference between the 15- and 30-minute groups. The other organs showed no significant differences compared to the control group. The groups to which ultrasound was applied showed increased serum AST and ALT levels, but the effects did not last for 30 min. Ultrasound-targeted nanobubble destruction was effective for doxorubicin delivery in the rat liver. The most effective ultrasound frequency and irradiation duration were 5 MHz and 15 min, respectively.

Boron neutron capture therapy (BNCT) is radiotherapy in which a nuclear reaction between boron-10 (10B) in tumor cells and neutrons produces alpha particles and recoiling 7Li nuclei with an extremely short range, leading to the destruction of the tumor cells. Although the neutron source has traditionally been a nuclear reactor, accelerators to generate neutron beams have been developed and commercialized. Therefore, this treatment will become more widespread. Recurrent head and neck cancer (HNC) close to the body surface is considered a candidate for BNCT using the boron compound boronophenylalanine (BPA) and has been found to be highly responsive to this treatment. However, some cases recur early after the completion of the treatment, which needs to be addressed. Ultrasound is a highly safe diagnostic method. Ultrasound with microbubbles is expected to promote the uptake of BPA into tumor cells. Ultrasound also has the ability to improve the sensitivity of tumor cells to radiotherapy. In addition, high-intensity focused ultrasound may improve the efficacy of BNCT via its thermal and mechanical effects. This review is not systematic but outlines the current status of BPA-based BNCT and proposes plans to reduce the recurrence rate of HNC after BNCT in combination with ultrasound.

This review explores a variety of techniques that utilize air injections beneath a vessel’s hull to reduce drag and consequently improve energy efficiency. It focuses on the methodologies of microbubble drag reduction (MBDR), air layer drag reduction (ALDR), and air cavity drag reduction (ACDR), offering insights into their design, operational mechanisms, and potential applications. This review provides a detailed examination of the underlying principles of these technologies, incorporating a blend of experimental research, numerical simulations, and mathematical modelling to offer a comprehensive understanding. It references recent experimental data, highlighting how these findings corroborate with numerical simulations and are further explained through mathematical models. Conclusively, this review accentuates the transformative influence of air injection methods in drag reduction within the maritime industry, emphasizing their pivotal role in boosting operational efficiency, reducing environmental impact, and driving the evolution of naval design and transportation. Through a balanced and detailed analysis, this review provides a holistic view of the current state and future prospects of these innovative resistance reduction strategies.

The classical microbubble generator of the venturi nozzle type is still used in a wide range of industries despite its relatively low performance. In this study, for overcoming the relatively low performances and maintaining the existing advantages, the cylindrical venturi type of microbubble generators with screw structures and flared diffusers are proposed using conventional 3D printers. In the experimental facility, flow rates and pressure drop were measured. Using high speed images, the performances were deduced for prepared microbubble generators. Based on experimental data, the effect of screw structures for performances of microbubble generators was identified. Furthermore, the flared diffuser to the diffuser of regular venturi nozzle with constant diverging angle were compared. Additionally, synergies are obtained by the screw structure in the flare diffuser. In conclusion, the performances of the venturi type microbubble generator through optimal designed screw structures by 39.4 % were improved. [ABSTRACT FROM AUTHOR]

Microbubbles are 10–100-μm bubbles with unique properties that find applications in chemical reactions, water aeration, sewage purification, biomedicine, skincare, and mineral flotation. Here, we review microbubbles with focus on basics, analysis, preparation, and applications. Microbubbles preparation can be done by lowering the pressure, by breaking the gas phase, or by electrochemistry. We present applications for improving gas–liquid reactions, wastewater treatment, mineral flotation, drug delivery, drinks, hyperoxia therapy, aquaculture, and agriculture. Industrial use of microbubbles is actually limited by the preparation of stable and uniformly sized microbubbles at large scale. [ABSTRACT FROM AUTHOR]

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There is an urgent need to realize precise clinical ultrasound with ultrasound contrast agents that provide high echo intensity and mechanical index tolerance. Graphene derivatives possess exceptional characteristics, exhibiting great potential in fabricating ideal ultrasound contrast agents. Herein, we reported a facile and green approach to synthesizing reduced graphene oxide with ellagic acid (rGO-EA). To investigate the application of a graphene derivative in ultrasound contrast agents, rGO-EA was dispersed in saline solution and mixed with SonoVue (SV) to fabricate SV@rGO-EA microbubbles. To determine the properties of the product, analyses were performed, including ultraviolet–visible spectroscopy (UV–vis), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), X-ray photoelectron spectrum (XPS), X-ray diffraction analysis (XRD) and zeta potential analysis. Additionally, cell viability measurements and a hemolysis assay were conducted for a biosafety evaluation. SV@rGO-EA microbubbles were scanned at various mechanical index values to obtain the B-mode and contrast-enhanced ultrasound (CEUS) mode images in vitro. SV@rGO-EA microbubbles were administered to SD rats, and their livers and kidneys were imaged in CEUS and B-mode. The absorption of rGO-EA resulted in an enhanced echo intensity and mechanical index tolerance of SV@rGO-EA, surpassing the performance of SV microbubbles both in vitro and in vivo. This work exhibited the application potential of graphene derivatives in the field of ultrasound precision medicine. [ABSTRACT FROM AUTHOR]

This study was to explore the activation of mast cells by microbubbles, with the focus on transient receptor potential (TRP) channels mediated degranulation and calcium influx. Bone marrow‐derived mast cells (BMMCs) were primarily obtained from femurs in mice and induced differentiation for 4 weeks. After the purity identification, BMMCs were contacted by homogeneous microbubbles with the diameter of 1 mm for 1 h. β‐hexosaminidase and histamine levels in supernatants were assessed by enzyme‐linked immunosorbent assay (ELISA) and the CD63 expression was tested by flow cytometry. The intracellular calcium binding with Fluo‐4 AM dyes in BMMCs was observed under the fluorescence microscope and the mean fluorescence intensity was quantitatively measured by flow cytometry. β‐hexosaminidase release, histamine concentration, CD63 expression and calcium influx were significantly increased in BMMCs group upon microbubble stimulation compared to the control groups. After preconditioning with the available inhibitors and microbubble contact, only transient receptor potential vanilloid 1 (TRPV1) and TRPV4 inhibitors robustly suppressed the microbubble‐induced degranulation. Likewise, the elevated fluorescence intensity of cytosolic calcium level was also significantly weaken. The results demonstrated microbubble stimulus effectively promoted BMMCs degranulation, which could be substantially restrained by inhibitors targeted for blocking TRPV1 or TRPV4 channel. The alternation of intracellular calcium level in BMMCs was consistent with the changes of degranulation capacity. It's suggested that the activation of BMMCs by microbubbles may involve specific TRP calcium dependent channels. [ABSTRACT FROM AUTHOR]

After the atmospheric hydrochloric acid leaching method is used to treat laterite ore and initially purify it, the extract that results often contains a significant amount of Fe2+ impurities. A novel metallurgical process has been proposed that utilizes microbubble aeration to oxidize Fe2+ ions in laterite hydrochloric acid lixivium, facilitating subsequent separation and capitalizing on the benefits of microbubble technology, including its expansive specific surface area, negatively charged surface attributes, prolonged stagnation duration, and its capacity to produce active oxygen. The study examined the impacts of aeration aperture, stirring speed, oxygen flow rate, pH value, and reaction temperature. Under optimized experimental conditions, which included an aeration aperture of 0.45 µm, stirring at 500 rpm, a bubbling flow rate of 0.4 L/min, pH level maintained at 3.5, and a temperature range of 75–85 °C, the oxidation efficiency of Fe2+ surpassed 99%. An analysis of the mass transfer process revealed that microbubble aeration markedly enhances the oxygen mass transfer coefficient, measured at 0.051 s−1. The study also confirmed the self-catalytic properties of Fe2+ oxidation and conducted kinetic studies to determine an apparent activation energy of 399 kJ/mol. At pH values below 3.5, the reaction is solely governed by chemical reactions; however, at higher pH values (>3.5), both chemical reactions and oxygen dissolution jointly control the reaction. [ABSTRACT FROM AUTHOR]

Microbubbles loaded with Rose Bengal and docetaxel (DTX-MB-RB) were more effective when activated using ultrasound than a standard dose of docetaxel. [Display omitted] Docetaxel (DTX) chemotherapy is commonly used in the treatment of patients with advanced prostate cancer demonstrating modest improvements in survival. As these patients are often elderly and the chemotherapy treatment is not targeted, it is often poorly tolerated. More targeted approaches that increase therapeutic efficacy yet reduce the amount of toxic chemotherapy administered are needed. In this manuscript, we investigate the potential of ultrasound targeted microbubble destruction (UTMD) to deliver a combination of docetaxel chemotherapy and Rose Bengal mediated sonodynamic therapy (SDT) in pre-clinical prostate cancer models. A Rose Bengal modified phospholipid was synthesized and used as a component lipid to prepare a microbubble (MB) formulation that was also loaded with DTX. The DTX-MB-RB formulation was used in the UTMD mediated treatment of androgen sensitive and androgen resistant 3D spheroid and murine models of prostate cancer. Results from the 3D spheroid experiments showed UTMD mediated DTX-MB-RB chemo-sonodynamic therapy to be significantly more effective at reducing cell viability than UTMD mediated DTX or SDT treatment alone. In an androgen sensitive murine model of prostate cancer, UTMD mediated DTX-MB-RB chemo-sonodynamic therapy was as effective as androgen deprivation therapy (ADT) at controlling tumour growth. However, when both treatments were combined, a significant improvement in tumour growth delay was observed. In an androgen resistant murine model, UTMD mediated DTX-MB-RB chemo-sonodynamic therapy was significantly more effective than standard DTX monotherapy. Indeed, the DTX dose administered using the DTX-MB-RB formulation was 91% less than standard DTX monotherapy. As a result, UTMD mediated DTX-MB-RB treatment was well tolerated while animals treated with DTX monotherapy displayed significant weight loss which was attributed to acute toxic effects. These results highlight the potential of UTMD mediated DTX-MB-RB chemo-sonodynamic therapy as a targeted, well tolerated alternative treatment for advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Glioblastoma is a highly invasive and fatal disease. Temozolomide, a blood–brain barrier (BBB)-penetrant therapeutic agent currently used for glioblastoma, does not exhibit sufficient therapeutic effect. Cisplatin (CDDP), a versatile anticancer drug, is not considered a therapeutic option for glioblastoma due to its low BBB permeability. We previously investigated the utility of microbubbles (MBs) in combination with ultrasound (US) in promoting BBB permeability and reported the efficacy of drug delivery to the brain using a minimally invasive approach. This study aimed to evaluate the feasibility of CDDP delivery to the brain using the combination of MBs and US for the treatment of glioblastoma. We used mice that were implanted with glioma-261 GFP-Luc cells expressing luciferase as the glioblastoma model. In this model, after tumor inoculation, the BBB opening was induced using MBs and US, and CDDP was simultaneously administered. We found that the CDDP concentrations were higher at the glioblastoma site where the US was applied, although CDDP normally cannot pass through the BBB. Furthermore, the survival was longer in mice treated with CDDP delivered via MBs and US than in those treated with CDDP alone or those that were left untreated. These results suggest that the combination of MBs and US is an effective antitumor drug delivery system based on BBB opening in glioblastoma therapy. [ABSTRACT FROM AUTHOR]

The effectiveness of thermal ablation for the treatment of liver tumours is limited by the risk of incomplete ablation, which can result in residual tumours. Herein, an enhancement strategy is proposed based on the controlled release of Ganoderma applanatum polysaccharide (GAP) liposome–microbubble complexes (GLMCs) via ultrasound (US)-targeted microbubble destruction (UTMD) and sublethal hyperthermic (SH) field. GLMCs were prepared by conjugating GAP liposomes onto the surface of microbubbles via biotin–avidin linkage. In vitro , UTMD promotes the cellular uptake of liposomes and leads to apoptosis of M2-like macrophages. Secretion of arginase-1 (Arg-1) and transforming growth factor-beta (TGF-β) by M2-like macrophages decreased. In vivo , restriction of tumour volume was observed in rabbit VX2 liver tumours after treatment with GLMCs via UTMD in GLMCs + SH + US group. The expression levels of CD68 and CD163, as markers of tumour-associated macrophages (TAMs) in the GLMCs + SH + US group were reduced in liver tumour tissue. Decreased Arg-1, TGF-β, Ki67, and CD31 factors related to tumour cell proliferation and angiogenesis was evident on histological analysis. In conclusion, thermal/US-triggered drug release from GLMCs suppressed rabbit VX2 liver tumour growth in the SH field by inhibiting TAMs, which represents a potential approach to improve the effectiveness of thermal ablation. [Display omitted] • A novel-designed drug carrier (GAP loaded liposome microbubble complex, GLMC) could be dual thermal/ultrasound-triggered. • Activity and population of TAMs were inhibited via delivery of GLMCs. • GLMCs could suppress rabbit VX2 liver tumour growth with no obvious toxicity. • GLMCs could be imaged on contrast-enhanced ultrasonography. • Potential for enhancing effects of thermal ablation on liver tumours. [ABSTRACT FROM AUTHOR]

Biaxial driving can more efficiently convert electrical power to forward acoustic power in piezoelectric materials, and the interaction between the orthogonal electric fields can produce a combination of extensional and shear deformations as a function of the phase difference between them to allow dynamic steering of the beam with a single-element. In this study, we demonstrate for the first time the application of a single-element biaxially driven ring transducer in vivo for blood–brain barrier opening in mice, and compare it to that achieved with a conventional single-element highly focused (F# = 0.7) spherical transducer operating at a similar frequency. Transcranial focused ultrasound (0.45 MPa, 10 ms pulse length, 1 Hz repetition frequency, 30 s duration) was applied bilaterally to mice with a 40 μ l/kg bolus of DefinityTM microbubbles, employing either a single-element biaxial ring (1.482 MHz, 10 mm inner diameter, 13.75 mm outer diameter) or spherical (1.5 MHz, 35 mm diameter, F# = 0.7; RK50, FUS Instruments) transducer on each side. Follow-up MRI scans (T1 pre- and post- 0.2 mmol/kg Gd injection, T2) were acquired to assess blood–brain barrier opening volume and potential damage. Compared to blood–brain barrier opening achieved with a conventional single-element spherical focused transducer, the opening volume achieved with a single-element biaxial ring transducer was 35% smaller (p = 0.002) with a device of a ring diameter of 40% the aperture size. Axial refocusing was further demonstrated with the single-element biaxial ring transducer, yielding a 1.63 mm deeper, five-fold larger opening volume (p = 0.048) relative to its small-focus mode. The biaxial ring transducer achieved a more localized opening compared to the spherical focused transducer under the same parameters, and further enabled dynamic axial refocusing with a single-element transducer with a smaller fabrication footprint. [ABSTRACT FROM AUTHOR]