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We perform large-scale atomistic simulations of a system containing 12 × 106 atoms, comprising an oxygen gas-filled bubble immersed in water, to understand the stability and cavitation induced by ultrasound. First, we propose a method to construct a bubble/water system. For a given bubble radius, the pressure inside the bubble is estimated using the Young–Laplace equation. Then, this pressure is used as a reference for a constant temperature, constant pressure simulation of an oxygen system, enabling us to extract a sphere of oxygen gas and place it into a cavity within an equilibrated water box. This ensures that the Young–Laplace equation is satisfied and the bubble is stable in water. Second, this stable bubble is used for ultrasound-induced cavitation simulations. We demonstrate that under weak ultrasound excitation, the bubble undergoes stable cavitation, revealing various fluid velocity patterns, including the first-order velocity field and microstreaming. These fluid patterns emerge around the bubble on a nanometer scale within a few nanoseconds, a phenomenon challenging to observe experimentally. With stronger ultrasound intensities, the bubble expands significantly and then collapses violently. The gas core of the collapsed bubble, measuring 3–4 nm, exhibits starfish shapes with temperatures around 1500 K and pressures around 6000 bar. The simulation results are compared with those from Rayleigh–Plesset equation modeling, showing good agreement. Our simulations provide insights into the stability and cavitation of nanosized bubbles. [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]

Objective. A reliable, calibrated, non-invasive thermometry method is essential for thermal therapies to monitor and control the treatment. Ultrasound (US) is an effective thermometry modality due to its relatively high sensitivity to temperature changes, and fast data acquisition and processing capabilities. Approach. In this work, the change in backscattered energy (CBE) was used to control the tissue temperature non-invasively using a real-time proportional-integral-derivative (PID) controller. A clinical high-frequency US scanner was used to acquire radio-frequency echo data from ex vivo porcine tissue samples and in vivo mice hind leg tissue while the tissue was treated with mild hyperthermia by a focused US applicator. The PID controller maintained the focal temperature at approximately 40 °C for about 4 min. Main results. The results show that the US thermometry based on CBE estimated by a high-frequency US scanner can produce 2D temperature maps of a localized heating region and to estimate the focal temperature during mild hyperthermia treatments. The CBE estimated temperature varied by an average of ±0.85 °C and ±0.97 °C, compared to a calibrated thermocouple, in ex vivo and in vivo studies, respectively. The mean absolute deviations of CBE thermometry during the controlled hyperthermia treatment were ±0.45 °C and ±0.54 °C in ex vivo and in vivo, respectively. Significance. It is concluded that non-invasive US thermometry via backscattered energies at high frequencies can be used for real-time monitoring and control of hyperthermia treatments with acceptable accuracy. This provides a foundation for an US mediated drug delivery system. [ABSTRACT FROM AUTHOR]

Sonoporation-based delivery has great promise for noninvasive drug and gene therapy. After short-term membrane resealing, the long-term function recovery of sonoporated cells affects the efficiency and biosafety of sonoporation-based delivery. It is necessary to identify the key early biological signals that influence cell fate and to develop strategies for manipulating the long-term fates of sonoporated cells. Here, we used a customized experimental platform with a single cavitating microbubble induced by a single ultrasound pulse (frequency: 1.5 MHz, pulse length:13.33 μs, peak negative pressure: ∼0.40 MPa) to elicit single-site reversible sonoporation on a single HeLa cell model. We used a living-cell microscopic imaging system to trace the long-term fates of sonoporated HeLa cells in real-time for 48 h. Fluorescence from intracellular propidium iodide and Fluo-4 was used to evaluate the degree of sonoporation and intracellular calcium fluctuation (ICF), respectively. Changes in cell morphology were used to assess the long-term cell fates (i.e., proliferation, arrest, or death). We found that heterogeneously sonoporated cells had different long-term fates. With increasing degree of sonoporation, the probability of normal (proliferation) and abnormal fates (arrest and death) in sonoporated cells decreased and increased, respectively. We identified ICF as an important early event for triggering different long-term fates. Reversibly sonoporated cells exhibited stronger proliferation and restoration at lower extents of ICF. We then regulated ICF dynamics in sonoporated cells using 2-APB or BAPTA treatment to reduce calcium release from intracellular organelles and enhance intracellular calcium clearance, respectively. This significantly enhanced the proliferation and restoration of sonoporated cells and reduced the occurrence of cell-cycle arrest and death. Finally, we found that the long-term fates of sonoporated cells at multiple sites and neighboring cells were also dependent on the extent of ICF, and that 2-APB significantly enhanced their viability and reduced death. Thus, using a single HeLa cell model, we demonstrated that regulating intracellular calcium can effectively enhance the proliferation and restoration capabilities of sonoporated cells, therefore rescuing the long-term viability of sonoporated cells. These findings add to our understanding of the biophysical process of sonoporation and help design new strategies for improving the efficiency and biosafety of sonoporation-based delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

Subcutaneous microbubble administration in connection with contrast enhanced ultrasound (CEUS) imaging is showing promise as a noninvasive and sensitive way to detect tumor draining sentinel lymph nodes (SLNs) in patients with breast cancer. Moreover, there is potential to harness the results from these approaches to directly estimate cancer burden, since some microbubble formulas, such as the Sonazoid used in this study, are rapidly phagocytosed by macrophages, and the macrophage concentration in a lymph node is inversely related to the cancer burden. This work presents a mathematical model that can approximate a rate constant governing macrophage uptake of Sonazoid, ki, given dynamic CEUS Sonazoid imaging data. Twelve healthy women were injected with 1.0 ml of Sonazoid in an upper-outer quadrant of one of their breasts and SLNs were imaged in each patient immediately after injection, and then at 0.25, 0.5, 1, 2, 4, 6, and 24 h after injection. The mathematical model developed was fit to the dynamic CEUS data from each subject resulting in a mean ± sd of 0.006 ± 0.005 h−1 and 0.4 ± 0.1 h−1 for relative lymphatic flow (EFl) and ki, respectively. Furthermore, the roughly 25% sd of the ki measurement was similar to the sd that would be expected from realistic noise simulations for a stable 0.4 h−1 value of ki, suggesting that macrophage concentration is highly consistent among cancer-free SLNs. These results, along with the significantly smaller variance in ki measurement observed compared to relative lymphatic flow suggest that ki may be a more precise and promising approach of estimating macrophage abundance, and inversely cancer burden. Future studies comparing tumor-free to tumor-bearing nodes are planned to verify this hypothesis. [ABSTRACT FROM AUTHOR]

To enhance the anesthetic efficacy and reduce toxic side effects, a strategy is proposed involving the utilization of general anesthetics of Propofol (Pro) and Etomidate (Eto) to synergistic inhibition GABA receptors simultaneously. Four‐in‐one molecular aggregates were prepared to implement this strategy, which comprised of Pro and Eto with the bridging molecule monoglyceride monooleate (GMO) and surfactant F127 through intermolecular forces. The blood‐brain barrier (BBB) targeted lactoferrin (LF) is affixed to their surface, obtaining the final molecular aggregates. By employing lactoferrin enrich aggregates to the BBB, followed by ultrasound combine microbubbles to open the BBB, a remarkable 4.5‐fold enhancement in brain drug delivery was achieved. The molecular aggregates group maintained stable parameters of heart rate, diastolic blood pressure, and systolic blood pressure. A notable increase of more than twice therapeutic index (TI) value was observed, implying their higher anesthesia efficiency and reduced toxicity. Electroencephalogram (EEG) experiments demonstrate a significant elevation in the proportion of δ waves from 28% to 80% for aggregates, accompanied by a nearly fivefold reduction in the proportion of θ waves, meaning a significant improvement in synergistic anesthesia effectiveness (interaction index 0.289) with lower drug dosage. Furthermore, mouse immunofluorescence brain slice experiments suggest Pro and Eto enter the GABA receptor simultaneously, resulting in synergistic inhibition of GABA receptors. [ABSTRACT FROM AUTHOR]

Transarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0–37.5 mg of Dox/mL of beads) is reported. Up to 400 microbubbles were bound to Dox-loaded beads (70–150 microns). This facilitated ultrasound imaging of the beads and increased the release rate of Dox upon exposure to high intensity focused ultrasound (HIFU). Furthermore, ultrasound exposure (1 MPa peak negative pressure) increased the distance at which Dox could be detected from beads embedded in a tissue-mimicking phantom, compared with a no ultrasound control. [ABSTRACT FROM AUTHOR]

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the performance and the impact of contrast-enhanced intraoperative ultrasound (CE-IOUS) on intraoperative decision-making, as there is still no standardized protocol for its use. Therefore, we retrospectively analyzed multiple CE-IOUS performed in hepato-pancreatic-biliary surgery with respect to pre- and postoperative imaging and histopathological findings. Methods: Data of 50 patients who underwent hepato-pancreatic-biliary surgery between 03/2022 and 03/2024 were retrospectively collected. CE-IOUS was performed with a linear 6–9 MHz multifrequency probe connected to a high-resolution device. The ultrasound contrast agent used was a stabilized aqueous suspension of sulphur hexafluoride microbubbles. Results: In total, all 50 lesions indicated for surgery were correctly identified. In 30 cases, CE-IOUS was used to localize the primary lesion and to define the resection margins. In the remaining 20 cases, CE-IOUS identified an additional lesion. Fifteen of these findings were identified as malignant. In eight of these cases, the additional malignant lesion was subsequently resected. In the remaining seven cases, CE-IOUS again revealed an inoperable situation. In summary, CE-IOUS diagnostics resulted in a high correct classification rate of 95.7%, with positive and negative predictive values of 95.2% and 100.0%, respectively. Conclusions: CE-IOUS shows excellent performance in describing intraoperative findings in hepato-pancreatic-biliary surgery, leading to a substantial impact on intraoperative decision-making. [ABSTRACT FROM AUTHOR]

Encapsulated microbubbles (EMBs) stabilized by thin coatings have been used as contrast agents for ultrasound sonography as well as having been demonstrated as a promising new technology for targeted drug delivery. The dynamics of EMBs is three-dimensional (3D) because EMBs within micro-vessels inevitably interact with boundaries, but the theoretical and numerical studies are limited to spherical, weakly non-spherical, and/or axisymmetric EMBs. Here, we have developed physical, mathematical, and numerical models for nonlinear 3D EMB dynamics. The liquid flow is evaluated using the boundary integral method. The EMB coating is modeled as a thin viscoelastic shell including stretching, bending, and shear effects and simulated using the finite element method. These models are coupled through the kinematic and dynamic boundary conditions at the interface. The model is in good agreement with the Hoff equation for spherical EMBs and the asymptotic theory for weakly non-spherical deformation of EMBs. Using this model, a numerical study for EMB dynamics near a rigid boundary subject to an ultrasonic wave is performed. The migration, non-spherical oscillation, resonant oscillation, and jetting of EMBs are displayed and analyzed systematically. If the ultrasound wave is strong, a high-speed liquid jet forms at the final stage of the collapse, orientated between the directions of the wave and toward the wall. The EMB jet is weaker and slower and has less momentum, as the non-spherical deformation of the coating and the jetting are suppressed by the viscoelastic property of the coating. If the ultrasound is not strong, the EMB remains spherical for many cycles of oscillation but the EMB undergoes resonant oscillation and becomes significantly non-spherical after several oscillation cycles, when the wave frequency is equal to its natural frequency. The numerical capability has the potential to be developed for the optimization of sonography or drug delivery. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective study, three dogs and three cats were selected from the database of the Chonnam National University Teaching Hospital from February 2017 to June 2019. The inclusion criteria for the selection of patients were as follows: (1) clinical data including age, sex, breed, clinical signs, histology, fine-needle aspiration, or fluid centesis were available and (2) intraluminal CEUS was performed; CEUS findings helped confirm the diagnosis. Each patient underwent physical examination, blood tests, radiography, and conventional ultrasonography. Intraluminal CEUS was performed using contrast agents, including SonoVue, agitated saline, saline, or a combination for GI hydrosonography in two patients and sono-cystourethrography in four patients. GI hydrosonography could assess the anatomic relationship between the mass and gastric lumen after administration of a mixture of 0.1 mL SonoVue and 30 mL/kg water in case 1 and could dilate the colonic lumen to detect the thickened wall using saline infusion in case 2. Upon sono-cystourethrography, communication between the urinary tract and prostatic cyst was clearly visualized in case 3, and narrowing of the urethral lumen secondary to prostatomegaly could be ruled out in case 4 with pyogranulomatous prostitis using agitated saline. The saline or agitated saline is appropriate for filling the lumen and improving the acoustic window for GI hydrosonography. Intraluminal CEUS examinations helped to assess the patency of the lumen, evaluate the extent of luminal dilation, rule out luminal narrowing, determine the presence of a mass within the lumen, and identify rupture sites. Administering intraluminal fluid can improve the acoustic window for the visualization of the lumen and wall layers in the cavitary organs. Microbubbles in ultrasound contrast agents can also be used for intracavitary applications to enhance visualization of the lesion in human patients. However, there was no literature extending the clinical application of intraluminal contrast-enhanced ultrasonography (CEUS) to patients with naturally occurring diseases in veterinary medicine. This case series aims to describe the detailed application and diagnostic value of intraluminal CEUS in six clinical cases with naturally occurring gastrointestinal (GI) and urinary tract diseases. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound could assess whether cancer chemotherapeutic agents work in days, rather than waiting 2–3 months, as is typical using the Response Evaluation Criteria in Solid Tumors (RECIST), therefore avoiding toxic side effects and expensive, ineffective therapy. A total of 40 mice were implanted with human colon cancer cells: treatment-sensitive mice in control (n = 10, receiving saline) and treated (n = 10, receiving bevacizumab) groups and treatment-resistant mice in control (n = 10) and treated (n = 10) groups. Each mouse was imaged using 3D dynamic contrast-enhanced ultrasound with Definity microbubbles. Curvature learning, an unsupervised learning approach, quantized pixels into three classes—blue, yellow, and red—representing normal, intermediate, and high cancer probability, both at baseline and after treatment. Next, a curvature learning score was calculated for each mouse using statistical measures representing variations in these three color classes across each frame from cine ultrasound images obtained during contrast administration on a given day (intra-day variability) and between pre- and post-treatment days (inter-day variability). A Wilcoxon rank-sum test compared score distributions between treated, treatment-sensitive mice and all others. There was a statistically significant difference in tumor score between the treated, treatment-sensitive group (n = 10) and all others (n = 30) (p = 0.0051). Curvature learning successfully identified treatment response, detecting changes in tumor perfusion before changes in tumor size. A similar technique could be developed for humans. [ABSTRACT FROM AUTHOR]

When a laser is focused on an underwater object, it experiences a large amount of pressure owing to the plasma confinement effect of water. A hemispherical bubble is generated on the surface of the object, and large pressure is generated when the bubble collapses. In this study, we conducted experiments using different laser energies to analyze the pressure–time histories associated with bubble contraction. The maximum pressure was 10%–40% of the laser ablation pressure, whereas the pressure pulse width was 5–10 times longer than the laser pulse width. Furthermore, the bubble motion could be adiabatically explained, except for the plasma interaction region. The results indicate that the pressure at which the bubble collapses does not depend on the maximum size of the generated bubble but depends on the energy of water vapor within the bubble. [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]

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]

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]

We report our experience disrupting the blood-brain barrier (BBB) to improve drug delivery in glioblastoma patients receiving temozolomide chemotherapy. The goals of this retrospective analysis were to compare MRI-based measures of BBB disruption and vascular damage to the exposure levels, acoustic emissions data, and acoustic simulations. We also simulated the cavitation detectors. Monthly BBB disruption (BBBD) was performed using a 220 kHz hemispherical phased array focused ultrasound system (Exablate Neuro, InSightec) and Definity microbubbles (Lantheus) over 38 sessions in nine patients. Exposure levels were actively controlled via the cavitation dose obtained by monitoring subharmonic acoustic emissions. The acoustic field and sensitivity profile of the cavitation detection system were simulated. Exposure levels and cavitation metrics were compared to the level of BBBD evident in contrast-enhanced MRI and to hypointense regions in T2*-weighted MRI. Our treatment strategy evolved from using a relatively high cavitation dose goal to a lower goal and longer sonication duration and ultimately resulted in BBBD across the treatment volume with minimal petechiae. Subsonication-level feedback control of the exposure using acoustic emissions also improved consistency. Simulations of the acoustic field suggest that reflections and standing waves appear when the focus is placed near the skull, but their effects can be mitigated with aberration correction. Simulating the cavitation detectors suggest variations in the sensitivity profile across the treatment volume and between patients. A correlation was observed with the cavitation dose, BBBD and petechial hemorrhage in 8/9 patients, but substantial variability was evident. Analysis of the cavitation spectra found that most bursts did not contain wideband emissions, a signature of inertial cavitation, but biggest contribution to the cavitation dose – the metric used to control the procedure – came from bursts with wideband emissions. Using a low subharmonic cavitation dose with a longer duration resulted in BBBD with minimal petechiae. The correlation between cavitation dose and outcomes demonstrates the benefits of feedback control based on acoustic emissions, although more work is needed to reduce variability. Acoustic simulations could improve focusing near the skull and inform our analysis of acoustic emissions. Monitoring additional frequency bands and improving the sensitivity of the cavitation detection could provide signatures of microbubble activity associated with BBB disruption that were undetected here and could improve our ability to achieve BBB disruption without vascular damage. A hemispherical ultrasound phased array was used to disrupt the BBB in glioblastoma patients. Left: targeted and disrupted volumes. Right: treatment plan and post-ultrasound contrast-enhanced MRI. [Display omitted] • We used focused ultrasound to disrupt the blood-brain barrier in glioma patients. • We found parameters that produced effective disruption with minimal side effects. • We demonstrated the potential utility of acoustic modeling of the treatments. • We show how acoustic emissions were related to the disruption and vascular damage. [ABSTRACT FROM AUTHOR]

Ultrasound examination is becoming the most popular medical imaging modality because of its low cost and high safety profile. Ultrasound contrast agents enhance the scattering of sound waves, which can improve the clarity and resolution of images. Nanoparticle Ultrasound contrast agents have the characteristics of a large specific surface area and a modifiable surface, which can increase drug loading capacity, prolong circulation time, and enable drug enrichment in specific organs or tissues. This leads to improved therapeutic effects and reducing toxic and side effects. Compared with traditional ultrasound contrast agents, Nano-ultrasound contrast agents overcome the limitation of imaging solely within blood vessels and facilitate imaging within tumor tissues, thereby extending the duration of enhanced imaging. Sonodynamic therapy is an emerging treatment method that has been developed rapidly in recent years, which has the advantages of noninvasive, high spatial and temporal resolution, and low toxicity and side effects. Sonodynamic therapy utilizes a sonosensitizer that, when excited by ultrasound at the tumor site, produces toxic reactive oxygen species, inducing apoptosis or necrosis in tumor cells. Ultrasound-guided sonodynamic therapy allows for real-time observation of lesions, is convenient and flexible, and is free of radiation exposure. With the use of nanomaterials as carriers, ultrasound-guided sonodynamic therapy has made significant strides. This study categorizes and summarizes the current research on acoustic sensitizer carrier materials, including carbon-based, silicon-based, peptide-based, iron-based, metal-organic frameworks, polymers, and liposomes. It concludes by highlighting the current challenges in the integration of ultrasound imaging with sonodynamic therapy and suggests future directions for clinical application development. [ABSTRACT FROM AUTHOR]

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]

Photothermal therapy (PTT) has garnered considerable attention as an attractive treatment tool for cancer due to precisely selective treatment and minimal side effects. The primary challenge of PTT, which hinders its widespread application, is the limited therapeutic depth. This limitation arises from optical scattering in biological tissues, causing inadequate heat distribution within the deep tissue. To overcome this challenge, ultrasound‐assisted PTT (ULTRA‐PTT) is proposed that leverages the temporary formation of gas bubbles induced by ultrasound within the light propagation path. These bubbles act as optical clearing agents, effectively reducing optical scattering in biological tissues. To facilitate ULTRA‐PTT, a dedicated handpiece consisting of a ring‐shaped ultrasound transducer and a laser delivery module is developed. In‐vivo experiments show that ULTRA‐PTT statistically outperforms conventional PTT in melanoma treatment, mostly due to its ability to deliver sufficient laser energy to deep‐seated cancer cells. These findings underscore the potential of ULTRA‐PTT to expand the clinical applications of PTT beyond local tumors occurring in superficial tissue. [ABSTRACT FROM AUTHOR]

Tumor starvation therapy utilizing glucose oxidase (GOx), has gained traction due to its non-invasive and bio-safe attributes. However, its effectiveness is often hampered by severe hypoxia in the tumor microenvironment (TME), limiting GOx's catalytic activity. To address this issue, a multifunctional nanosystem based on mesoporous polydopamine nanoparticles (MPDA NPs) was developled to alleviate TME hypoxia. This nanosystem integrated GOx modification and oxygenated perfluoropentane (PFP) encapsulation to address hypoxia-related challenges in the TME. Under NIR laser irradiation, the MPDA NPs exhibit significant photothermal conversion efficacy, activating targeted tumor photothermal therapy (PTT), while also serving as proficient photoacoustic (PA) imaging agents. The ensuing temperature rise facilitates oxygen (O 2) release and induces liquid-gas conversion of PFP, generating microbubbles for enhanced ultrasound (US) imaging signals. The supplied oxygen alleviates local hypoxia, thereby enhancing GOx-mediated endogenous glucose consumption for tumor starvation. Overall, the integration of ultrasound/photoacoustic dual imaging-guided PTT and starvation therapy within MPDA-GOx@PFP@O 2 nanoparticles (MGPO NPs) presents a promising platform for enhancing the efficacay of tumor treatment by overcoming the complexities of the TME. A multifunctional MPDA-based theranostic nanoagent was developed for US/PAI imaging-guided PTT and starvation therapy against tumor hypoxia by direct O 2 delivery. The incorporation of oxygenated perfluoropentane (PFP) within the mesoporous structure of MGPO not only enables efficient US imaging but also helps in alleviating tumor hypoxia. Moreover, the strong near-infrared (NIR) absorption of MGPO NPs promote the generation of PFP microbubbles and release of oxygen, thereby enhancing US imaging and GOx-mediated starvation therapy. Such a multifunctional nanosystem leverages synergistic effects to enhance therapeutic efficacy while incorporating US/PA imaging for precise visualization of the tumor. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective. Super-resolution ultrasonography offers the advantage of visualization of intricate microvasculature, which is crucial for disease diagnosis. Mapping of microvessels is possible by localizing microbubbles (MBs) that act as contrast agents and tracking their location. However, there are limitations such as the low detectability of MBs and the utilization of a diluted concentration of MBs, leading to the extension of the acquisition time. We aim to enhance the detectability of MBs to reduce the acquisition time of acoustic data necessary for mapping the microvessels. Approach. We propose utilizing phase patterned waves (PPWs) characterized by spatially patterned phase distributions in the incident beam to achieve this. In contrast to conventional ultrasound irradiation methods, this irradiation method alters bubble interactions, enhancing the oscillation response of MBs and generating more significant scattered waves from specific MBs. This enhances the detectability of MBs, thereby enabling the detection of MBs that were undetectable by the conventional method. The objective is to maximize the overall detection of bubbles by utilizing ultrasound imaging with additional PPWs, including the conventional method. In this paper, we apply PPWs to ultrasound imaging simulations considering bubble–bubble interactions to elucidate the characteristics of PPWs and demonstrate their efficacy by employing PPWs on MBs fixed in a phantom by the experiment. Main results. By utilizing two types of PPWs in addition to the conventional ultrasound irradiation method, we confirmed the detection of up to 93.3% more MBs compared to those detected using the conventional method alone. Significance. Ultrasound imaging using additional PPWs made it possible to increase the number of detected MBs, which is expected to improve the efficiency of bubble detection. [ABSTRACT FROM AUTHOR]

The distorted Born iterative (DBI) method is considered to obtain images with high-contrast and resolution. Besides satisfying the Born approximation condition, the frequency-hopping (FH) technique is necessary to gradually update the sound contrast from the first iteration and progress to the actual sound contrast of the imaged object in subsequent iterations. Inspired by the fact that the higher the frequency, the higher the resolution. Because low-frequency allows for low-resolution object imaging, hence for high-resolution imaging requirements, using low-frequency to possess a high-resolution image from the first iteration will be less efficient. For an effective reconstruction, the object's resolution at low frequencies should be small. And similarly, with high frequencies, the object resolution should be larger. Therefore, in this paper, the FH, and the resolution-turning (RT) technique are proposed to obtain object images with high-contrast and -resolution. The convergence speed in the initial iterations is rapidly achieved by utilizing low frequency in the frequency-turning technique and low image resolution in the resolution-turning technique. It is crucial to ensure accurate object reconstruction for subsequent iterations. The desired spatial resolution is attained by employing high frequency and large image resolution. The resolution-turning distorted Born iterative (RT-DBI) and frequency-hopping distorted Born iterative (FH-DBI) solutions are thoroughly investigated to exploit their best performance. This makes sense because if it is not good to choose the number of iterations for the frequency f1 in FH-DBI and for the resolution of N1 × N1 in RT-DBI, then these solutions give even worse quality than traditional DBI. After that, the RT-FH-DBI integration was investigated in two sub-solutions. We found that the lower frequency f1 used both before and after the RT would get the best performance. Consequently, compared to the traditional DBI approaches, the normalized error and total runtime for the reconstruction process were dramatically decreased, at 83.6% and 18.6%, respectively. Besides fast and quality imaging, the proposed solution RT-FH-DBI is promised to produce high-contrast and high-resolution object images, aiming at object reconstruction at the biological tissue. The development of 3D imaging and experimental verification will be studied further. [ABSTRACT FROM AUTHOR]

Fluorescent dyes, or fluorophores, enable researchers to visualize specific biological molecules by fluorescence microscopy. Herein, a novel fluorescent FITC-poly(amidoamine) (FITC-PAMAM) dendrimers have been synthesized via divergent approach. The molecular structure of the FITC-PAMAM dendrimers (G-0 to G5) was characterized by 1H NMR, 13C NMR spectroscopy and by FTIR. In order to emphasize the structural efficacy of FITC-PAMAM dendrimer, the drug delivery behavior has been evaluated by using 5-fluorouracil (5-FU) as a model cancer therapy drug. Anti-proliferative activity of FITC-cored PAMAM dendrimers in all generations (G0-G5) with or without 5-FU were analyzed on human gastric carcinoma cells (AGS) by WST-1 cell proliferation assay. Initially, the nontoxic dose of unloaded FITC-PAMAM dendrimers was assessed for further drug loading experiments. Loading of 5-FU into FITC-PAMAM dendrimers, regardless of generation, increased the toxicity of the drug. Besides, 5-FU loaded FITC-PAMAM dendrimers induced a generation-based gradual inhibition of cell proliferation. FITC and phase contrast merged images indicated that FITC-PAMAM dendrimers facilitate the entry of the drug into the cells, in a generation-dependent manner. The FITC- dendrimers may serve as a promising intracellular drug delivery agent for 5-FU by increasing cell uptake into cells and thereby, enhancing antiproliferative activity on AGS cells in a generation-dependent manner. [ABSTRACT FROM AUTHOR]

Safe and accurate in situ delivery of biocompatible materials is a fundamental requirement for many biomedical applications. These include sustained and local drug release, implantation of acellular biocompatible scaffolds, and transplantation of cells and engineered tissues for functional restoration of damaged tissues and organs. The common practice today includes highly invasive operations with major risks of surgical complications including adjacent tissue damage, infections, and long healing periods. In this work, a novel non‐invasive delivery method is presented for scaffold, cells, and drug delivery deep into the body to target inner tissues. This technology is based on acousto‐sensitive materials which are polymerized by ultrasound induction through an external transducer in a rapid and local fashion without additional photoinitiators or precursors. The applicability of this technology is demonstrated for viable and functional cell delivery, for drug delivery with sustained release profiles, and for 3D printing. Moreover, the mechanical properties of the delivered scaffold can be tuned to the desired target tissue as well as controlling the drug release profile. This promising technology may shift the paradigm for local and non‐invasive material delivery approach in many clinical applications as well as a new printing method – "acousto‐printing" for 3D printing and in situ bioprinting. [ABSTRACT FROM AUTHOR]

Starch derived from plants plays an essential role in pharmaceuticals due to its components Amylose and Amylopectin, which form essential granules for drug delivery. Its biocompatibility and cost-effectiveness make it indispensable in pharmaceutical formulations, facilitating controlled drug release and tablet breakdown. The effectiveness and safety of drug formulations are often hindered by challenges such as low solubility and stability. In order to overcome these obstacles, current research is focused on modifying the properties of starch. The goal is to improve its solubility, swelling, erosion, stability, and ability to release drugs. A promising solution that has emerged is ultrasound-based modification. This technique has shown great potential in transforming starch granules, leading to improved solubility, degradability, and control over drug release. Not only is this method efficient and quick, but it also has the added benefit of being eco-friendly. This discussion will explore the mechanisms behind the modification of starch based on ultrasound, delving into both the physical and chemical changes that occur in starch granules. The analysis explores the utilization of modified starch induced by ultrasound in the field of drug delivery, investigating its stability and compatibility with biological systems. By exploring the capabilities and difficulties associated with the use of ultrasound to change starch for the delivery of drugs, we highlighted its potential as a leading and effective methodology. [ABSTRACT FROM AUTHOR]

Ultrasound-induced optical clearing microscopy (US-OCM) addresses limited imaging depth in optical microscopy, caused by light scattering in biological tissues. It uses ultrasound-induced gas bubbles to better image biological samples. However, controlling the bubble location using only ultrasound is challenging. This study introduces a novel method, "optrasound," combining optical and ultrasound energies for precise bubble control. It presents the ultrasound field and uses a focused laser to trigger bubble formation. Optrasound-induced deep microscopy improves light beam width by 3.39 times at a depth of 350 µm because the gas bubbles reduce light scattering. This technique can precisely localize a bubble cloud while matching the US-OCM performance. [ABSTRACT FROM AUTHOR]

The aim of the study is to develop the synthesis of a novel series of potent anti-tubercular (anti-TB) activity of 1,3-diphenylpyrazole-based spirooxindolopyrrolizidine derivatives via an efficient green approach achieved by using an ionic liquid ([Bmim]BF4) under ultrasonication. The title compounds 4a–4ad with a general molecular formula CaHbX(0–2)NcOd (X = F/Cl/Br) were produced with high yields in shorter reaction time and well characterized by using spectral techniques; and finally single crystal X-ray diffraction method (4b). The newly synthesized compounds were evaluated for their in vitro anti-TB activity against Mycobacterium tuberculosis H37Rv strain. Among all, six compounds 4e (C36H29N5O4), 4g (C34H28N4O3), 4q (C36H28F2N4O2), 4r (C36H28ClFN4O2), 4y (C36H29BrN4O2) and 4z (C36H28BrFN4O2) exhibited significant anti-TB activity with MIC value 6.25 μg mL−1, when compared to the standard drug ethambutol (MIC:1.56 μg mL−1). In silico molecular docking studies were performed against M. tuberculosis enoyl–acyl carrier protein reductase inhibitor. The compounds 4o, 4p, 4y and 4aa were exhibited least binding energies −12.58, −12.61, −12.58 and −12.57 kcal mol−1, respectively. These results reveal that the produced compounds might be used for the future generation of novel anti-TB drugs. [ABSTRACT FROM AUTHOR]

Early damage in metal materials is primarily characterized by microdefects, such as microcracks and micropores. In this study, we developed a novel approach for quantitatively assessing the microdefect damage degree in dual-phase bainite–ferrite (B + F) X80 pipeline steel using ultrasound nonlinear parameters. A finite element analysis model with micron-scale three-dimensional ellipsoidal defects was established based on the Gurson–Tvergaard–Needleman material damage theory. The propagation process of Lamb waves in the model was simulated to investigate the interaction mechanism between microdefects and Lamb waves and explore the quantitative relationship between ultrasound nonlinearity and microdefect damage degree, which can be characterized by the size and number of microdefects. Furthermore, to validate the simulation findings, an ultrasound testing experiment was designed to evaluate the microdefect damage in (B + F) X80 pipeline steel. The results demonstrate that when Lamb waves propagate through microdefects, their amplitude is attenuated, resulting in changes in ultrasound nonlinear parameters. Within a specific range, the nonlinear coefficient of Lamb waves increases with an increase in microdefect length and number of microdefects but decreases with an increase in microdefect width. This finding holds significant value for evaluating damage degree and predicting the service life of X80 pipeline steel. [ABSTRACT FROM AUTHOR]

To investigate the expulsion effect of different expulsion modes on Hexagrammos otakii, this study examined various environmental conditions in an indoor tank. Specifically, different lighting conditions (white, blue, and green light at illumination intensities of 5000 lx, 8000 lx, and 10000 lx) were explored, as well as varied sound conditions (sound frequencies of 150 Hz, 300 Hz, and 450 Hz at different sound pressure levels of 130 dB, 140 dB, and 150 dB) and bubble curtain conditions (air volumes of 60 L/min, 120 L/min, and 180 L/min). Additionally, the expulsion effect of different fish densities (1.56 tails/m², 2.35 tails/m², 3.13 tails/m²) of Hexagrammos otakii was investigated. The findings revealed that the bubble curtain exhibited the most effective expulsion effect on Hexagrammos otakii, with an expulsion rate of (40.4 ± 12.0) %, the highest period of 53%, and an average expulsion distance of 3.0 expulsion intervals when the air volume was 180 L/min and the fish density was 1.56 tails/m². Conversely, the expulsion effect of light and sound on Hexagrammos otakii was found to be insignificant, with the expulsion rate of sound not exceeding 20% and that of light being lower than 15%. These results have implications for the selection and design of fish expulsion equipment in offshore areas, such as those surrounding wind farms and nuclear power plants. Therefore, this study provides valuable scientific reference for resource managers and practitioners in the field. [ABSTRACT FROM AUTHOR]

This review discusses the current progress in the clinical use of magnetic resonance-guided focused ultrasound (MRgFUS) and other ultrasound platforms to transiently permeabilize the blood-brain barrier (BBB) for drug delivery in neurological disorders and neuro-oncology. Safety trials in humans have followed on from extensive pre-clinical studies, demonstrating a reassuring safety profile and paving the way for numerous translational clinical trials in Alzheimer's disease, Parkinson's disease, and primary and metastatic brain tumors. Future directions include improving ultrasound delivery devices, exploring alternative delivery approaches such as nanodroplets, and expanding the application to other neurological conditions. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a cytosine–adenine–guanine (CAG) trinucleotide repeat expansion in the HTT gene. There are no cures for HD, but the genetic basis of this disorder makes gene therapy a viable approach. Adeno-associated virus (AAV)-miRNA-based therapies have been demonstrated to be effective in lowering HTT mRNA; however, the blood–brain barrier (BBB) poses a significant challenge for gene delivery to the brain. Delivery strategies include direct injections into the central nervous system, which are invasive and can result in poor diffusion of viral particles through the brain parenchyma. Focused ultrasound (FUS) is an alternative approach that can be used to non-invasively deliver AAVs by temporarily disrupting the BBB. Here, we investigate FUS-mediated delivery of a single-stranded AAV9 bearing a cDNA for GFP in 2-month-old wild-type mice and the zQ175 HD mouse model at 2-, 6-, and 12-months. FUS treatment improved AAV9 delivery for all mouse groups. The delivery efficacy was similar for all WT and HD groups, with the exception of the zQ175 12-month cohort, where we observed decreased GFP expression. Astrocytosis did not increase after FUS treatment, even within the zQ175 12-month group exhibiting higher baseline levels of GFAP expression. These findings demonstrate that FUS can be used to non-invasively deliver an AAV9-based gene therapy to targeted brain regions in a mouse model of Huntington's disease. [ABSTRACT FROM AUTHOR]

Microswimmers are considered promising candidates for active cargo delivery to benefit a wide spectrum of biomedical applications. Yet, big challenges still remain in designing the microswimmers with effective propelling, desirable loading and adaptive releasing abilities all in one. Inspired by the morphology and biofunction of spermatozoa, we report a one-step formation strategy of polymorphous sperm-like magnetic microswimmers (PSMs) by developing a vortex turbulence-assisted microfluidics (VTAM) platform. The fabricated PSM is biodegradable with a core-shell head and flexible tail, and their morphology can be adjusted by vortex flow rotation speed and calcium chloride solution concentration. Benefiting from the sperm-like design, our PSM exhibits both effective motion ability under remote mag/netic actuation and protective encapsulation ability for material loading. Further, it can also realize the stable sustain release after alginate-chitosan-alginate (ACA) layer coating modification. This research proposes and verifies a new strategy for the sperm-like microswimmer construction, offering an alternative solution for the target delivery of diverse drugs and biologics for future biomedical treatment. Moreover, the proposed VTAM could also be a general method for other sophisticated polymorphous structures fabrication that isn't achievable by conventional laminar flow. Microswimmers are promising candidates for various biomedical applications. Inspired by spermatozoa, Tan et al. report a one-step strategy to fabricate biodegradable sperm-like magnetic microswimmers with both propelling and cargo delivery functions in a vortex turbulence assisted microfluidic chip. [ABSTRACT FROM AUTHOR]

Bubble columns are widely used in numerous industrial processes because of their advantages in operation, design, and maintenance compared to other multiphase reactor types. In contrast to their simple design, the generated flow conditions inside a bubble column reactor are quite complex, especially in continuous mode with counter-current liquid flow. For the design and optimization of such reactors, precise numerical simulations and modelling are needed. These simulations and models have to be validated with experimental data. For this reason, experiments were carried out in a laboratory-scale bubble column using shadow imaging and particle image velocimetry (PIV) techniques with and without counter-current liquid flow. In the experiments, two types of gases—relatively poorly soluble air and well-soluble CO2—were used and the bubbles were generated with three different capillary diameters. With changing gas and liquid flow rates, overall, 108 different flow conditions were investigated. In addition to the liquid flow fields captured by PIV, shadow imaging data were also statistically evaluated in the measurement volume and bubble parameters such as bubble diameter, velocity, aspect ratio, bubble motion direction, and inclination. The bubble slip velocity was calculated from the measured liquid and bubble velocities. The analysis of these parameters shows that the counter-current liquid flow has a noticeable influence on the bubble parameters, especially on the bubble velocity and motion direction. In the case of CO2 bubbles, remarkable bubble shrinkage was observed with counter-current liquid flow due to the enhanced mass transfer. The results obtained for bubble aspect ratio are compared to known correlations from the literature. The comprehensive and extensive bubble data obtained in this study will now be used as a source for the development of correlations needed in the validation of numerical simulations and models. The data are available from the authors on request. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the interactions between microbubbles and microwave ablation (MWA). Methods: The study employed custom‐made phantoms (in vitro) and white New Zealand rabbits (in vivo). MWA was performed with or without microbubbles in the phantoms (2 × 105 particles mL−1) and rabbit livers (intravenous injection of 0.05 mL/kg SonoVue). During the MWA, K‐type thermocouple probes were used to monitor the MWA‐induced temperature increase. Contrast‐enhanced ultrasound imaging (CEUS) was used to monitor and analyze the microbubbles signal intensity. After MWA, the ablation‐zone volumes were evaluated and compared between the groups with and without microbubbles. Results: In both the phantom models and rabbits, microbubbles showed no significant influence on MWA, including the ablation range and MWA‐induced temperature increase. In phantoms and rabbit livers filled with microbubbles, MWA caused the formation of a gradually expanding microbubble‐defect region over the ablation time. An increase in the temperature caused microbubble destruction. Conclusions: Microbubbles had no significant influence on MWA. However, MWA induced the destruction of microbubbles in a temperature‐dependent manner. Thus, the poor thermotolerance of microbubbles is a non‐negligible barrier when using CEUS to monitor the ablation range during MWA in real‐time. [ABSTRACT FROM AUTHOR]

Nanodrugs capable of aggregating in the tumor microenvironment (TME) have demonstrated great efficiency in improving the therapeutic outcome. Among various approaches, the strategy utilizing electrostatic interaction as a driving force to achieve intratumor aggregation of nanodrugs has attracted great attention. However, the great difference between the two nanodrugs with varied physicochemical properties makes their synchronous transport in blood circulation and equal‐opportunity tumor uptake impossible, which significantly detracts from the beneficial effects of nanodrug aggregation inside tumors. We herein propose a new strategy to construct a pair of extremely similar nanodrugs, referred to as "twins‐like nanodrugs (TLNs)", which have identical physicochemical properties including the same morphology, size, and electroneutrality to render them the same blood circulation time and tumor entrance. The 1:1 mixture of TLNs (TLNs‐Mix) intravenously injected into a mouse model efficiently accumulates in tumor sites and then transfers to oppositely charged nanodrugs for electrostatic interaction‐driven coalescence via responding to matrix metalloproteinase‐2 (MMP‐2) enriched in tumor. In addition to enhanced tumor retention, the thus‐formed micron‐sized aggregates show high echo intensity essential for ultrasound imaging as well as ultrasound‐triggered penetrative drug delivery. Owing to their distinctive features, the TLNs‐Mix carrying sonosensitizer, immune adjuvant, and ultrasound contrast agent exert potent sonodynamic immunotherapy against hypovascular hepatoma, demonstrating their great potential in treating solid malignancies. [ABSTRACT FROM AUTHOR]

As a natural cationic peptide, Nisin is capable of widely inhibiting the growth of Gram-positive bacteria. However, it also has drawbacks such as its antimicrobial activity being susceptible to environmental factors. Nano-encapsulation can improve the defects of nisin in food applications. In this study, nisin-loaded egg white protein nanoparticles (AH-NEn) were prepared in fixed ultrasound-mediated under pH 3.0 and 90 °C. Compared with the controls, AH-NEn exhibited smaller particle size (112.5 ± 2.85 nm), smaller PDI (0.25 ± 0.01), larger Zeta potential (24 ± 1.18 mV), and higher encapsulation efficiency (91.82%) and loading capacity (45.91%). The turbidity and Fourier transform infrared spectroscopy (FTIR) results indicated that there are other non-covalent bonding interactions between the molecules of AH-NEn besides the electrostatic forces, which accounts for the fact that it is structurally more stable than the controls. In addition, by the results of fluorescence intensity, differential scanning calorimetry (DSC), and X-ray diffraction (XRD), it was shown that thermal induction could improve the solubility, heat resistance, and encapsulation of nisin in the samples. In terms of antimicrobial function, acid–heat induction did not recede the antimicrobial activity of nisin encapsulated in egg white protein (EWP). Compared with free nisin, the loss rate of bactericidal activity of AH-NEn was reduced by 75.0% and 14.0% following treatment with trypsin or a thermal treatment at 90 °C for 30 min, respectively. [ABSTRACT FROM AUTHOR]

Traditional brining methods, such as immersion, are time‐consuming and affect the quality of the food product. Thus, high‐intensity ultrasound (HIUS) has been studied as a brining‐assisted non‐thermal technology. However, this approach to shrimp and the assessment of the individual and combined effects of HIUS parameters, for example, time (t), power (P), and salt concentration (SC), is a knowledge gap. This study aimed to model HIUS‐brining for improving salt diffusion and water properties while maintaining relevant purchase attributes closer to fresh shrimp (Penaeus vannamei) quality. Our findings suggest HIUS improves salt diffusion, decreasing Aw and enhancing water‐holding capacity (WHC). Instead, the increased P reduced hardness and enhanced whiteness. HIUS‐brining (22.02 min/267.89 W/6.68%) maximized Na+ (2.58%) and WHC (86.31%), minimized Aw (.92), and retained hardness (71.07 N) and whiteness (55.14) close to freshness. Therefore, it is possible to employ HIUS in the shrimp brine to improve salt diffusion without damaging physicochemical attributes. Practical applications: Despite traditional methods for seafood brining being considered effective, they are time‐consuming, taking hours to reach the desirable moisture value. High‐intensity ultrasound (HIUS) is an emerging non‐thermal technology recently explored as a brining technology for animal‐origin food, such as meat. The cavitation induced by HIUS generates gas microbubbles. The implosion increases local temperature and pressure and generates microjets, facilitating the mass transfer (sponge effect) and salt diffusion in the muscle tissues. However, the cavitation mechanism also releases free radicals, resulting in physicochemical alterations during processing, such as damage to color and texture. The present research contributes to providing a better understanding of the application and optimization of HIUS to accelerate the shrimp brining process. The findings herein are promising for the industrial utilization of sonication to obtain brined products without damaging the quality attributes of shrimp. [ABSTRACT FROM AUTHOR]

In order to explore the effect of magnetization on bubble motion behavior under different flotation agent systems, the three reagent solutions of sodium oleate, pineol oil and secoctanol were magnetized by laboratory self-made magnetization device, and the influence of magnetization on them was summarized by observing the bubbles generated in the self-made sink. The test results showed that the maximum velocity of bubbles under the sodium oleate system increased by 7.85 mm/s, the acceleration increased by 97 mm/s², the deformation coefficient of bubbles decreased by 0.19, the bubble merger time and bubble beating times increased by 0.25 s and 74 ms respectively compared with the unmagnetized conditions, and the bubble merger and bubble beating time changes significantly and the maximum speed increased by 9.43 mm/s when the magnetic induction intensity of the bubbles under the pine oil system was 100 mT. Under the secoctanol system, the bubble merger and bubble beating time changed significantly when the magnetic induction intensity was 150 mT, and the maximum velocity of the bubble increased by 3.03 mm/s at 300 mT. The experiments show that the magnetization treatment with 150 mT magnetic induction intensity has a favorable effect on the flotation behavior of sodium oleate solution. The largest differences in bubble deformation coefficient and beating time under sodium oleate, pineol oil and sec-octanol were at 150, 100 and 150 mT, respectively, and the influence of magnetic induction intensity on bubble velocity was also different under different solution systems. In addition, the rate of rise of sodium oleate has two peaks, while pineol oil and secoctanol have only one peak. Magnetization has obvious effects on all three solutions, and the research results have certain guiding significance for optimizing the application of magnetization treatment in flotation. [ABSTRACT FROM AUTHOR]

Objective: Minimally invasive surgery for spontaneous intracerebral hemorrhage is impeded by inadequate lysis of the target blood clot. Ultrasound is thought to expedite intravascular thrombolysis, thereby facilitating vascular recanalization. However, the impact of ultrasound on intracerebral blood clot lysis remains uncertain. This study aimed to explore the feasibility of combining ultrasound with urokinase to enhance blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage. Methods: The blood clots were divided into four groups: control group, ultrasound group, urokinase group, and ultrasound + urokinase group. Using our experimental setup, which included a key-shaped bone window, we simulated a minimally invasive puncture and drainage procedure for spontaneous intracerebral hemorrhage. The blood clot was then irradiated using ultrasound. Blood clot lysis was assessed by weighing the blood clot before and after the experiment. Potential adverse effects were evaluated by measuring the temperature variation around the blood clot in the ultrasound + urokinase group. Results: A total of 40 blood clots were observed, with 10 in each experimental group. The blood clot lysis rate in the ultrasound group, urokinase group, and ultrasound + urokinase group (24.83 ± 4.67%, 47.85 ± 7.09%, 61.13 ± 4.06%) was significantly higher than that in the control group (16.11 ± 3.42%) (p = 0.02, p < 0.001, p < 0.001). The blood clot lysis rate in the ultrasound + urokinase group (61.13 ± 4.06%) was significantly higher than that in the ultrasound group (24.83 ± 4.67%) (p < 0.001) or urokinase group (47.85 ± 7.09%) (p < 0.001). In the ultrasound + urokinase group, the mean increase in temperature around the blood clot was 0.26 ± 0.15°C, with a maximum increase of 0.38 ± 0.09°C. There was no significant difference in the increase in temperature regarding the main effect of time interval (F = 0.705, p = 0.620), the main effect of distance (F = 0.788, p = 0.563), or the multiplication interaction between time interval and distance (F = 1.100, p = 0.342). Conclusions: Our study provides evidence supporting the enhancement of blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage through the combined use of ultrasound and urokinase. Further animal experiments are necessary to validate the experimental methods and results. [ABSTRACT FROM AUTHOR]

The inflammatory damage caused by thrombus formation and dissolution can increase the risk of thrombotic complications on top of cell death and organ dysfunction caused by thrombus itself. Therefore, a rapid and precise thrombolytic therapy strategy is in urgent need to effectively dissolve thrombus and resist oxidation simultaneously. In this study, Ce‐UiO‐66, a cerium‐based metal–organic framework (Ce‐MOF) with reactive oxygen species (ROS) scavenging properties, encapsulated by low‐immunogenic mesenchymal stem cell membrane with inflammation‐targeting properties, is used to construct a targeted nanomedicine Ce‐UiO‐CM. Ce‐UiO‐CM is applied in combination with external ultrasound stimulation for thrombolytic therapy in rat femoral artery. Ce‐UiO‐66 has abundant Ce (III)/Ce (IV) coupling sites that react with hydrogen peroxide (H2O2) to produce oxygen, exhibiting catalase (CAT) activity. The multi‐cavity structure of Ce‐UiO‐66 can generate electron holes, and its pore channels can act as micro‐reactors to further enhance its ROS scavenging capacity. Additionally, the porous structure of Ce‐UiO‐66 and the oxygen produced by its reaction with H2O2 may enhance the cavitation effects of ultrasound, thereby improving thrombolysis efficacy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems. Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway, but are limited to their easy agglomeration and colloidal morphology, which makes it difficult to exert effects on low delivery efficiency. OBJECTIVE: To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles. METHODS: The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold. The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized. The microstructure, porosity, permeability, rheology, in vitro hemostasis, and antibacterial properties of the composite hydrogel were characterized. The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining, and the optimization effects of low-intensity pulsed ultrasound on the permeability, porosity, and mechanical properties of hydrogel were evaluated. RESULTS AND CONCLUSION: (1) Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers. The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability. (2) Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility. (3) Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure, and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation. The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials. The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@ methylacrylylated gelatin hydrogel scaffold. Under the irradiation of low-intensity pulsed ultrasound, the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties. (4) Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles, and more uniform dispersion could be obtained under ultrasonic excitation. (5) The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets, which showed stronger mechanical properties. The elongation at break was 122%, and the ductility was better than that without gold nanoparticles-nanodroplets (P < 0.05). (6) These findings indicate that the composite hydrogel scaffold has good biocompatibility, antibacterial property, oxidation resistance, and hemostatic effect. [ABSTRACT FROM AUTHOR]

Cancer is a serious health problem to be solved. With the development of biomaterials, enhanced diagnostic and controllable therapeutic strategies for cancer have emerged, revealing encouraging results with a promising future. Due to its outstanding tissue penetration and controllability, along with a series of bioeffects on tissues, ultrasound (US), as a common medical technology, has been regarded as an effective tool against cancer, and its use has promoted the exploration of US‐sensitive biomaterials. In this review, the bioeffects of US are first introduced and then the main US‐sensitive biomaterials (containing cavitation nuclei, sonosensitizers, and US‐responsive macromolecular systems) used to treat cancer, followed by a summary of several applications based on US‐sensitive biomaterials, from diagnosis to therapy. Finally, the emerging challenges in this field that need to be overcome are highlighted. This review reports the progress of US‐sensitive biomaterials, providing new possibilities in cancer theranostics and thus benefiting patients. [ABSTRACT FROM AUTHOR]

Microalgae have rigid, complex cell walls hindering direct lipid extraction. Cell disruption techniques are used to rupture these cellular structures to increase lipid extraction. Researchers investigating the downstreamprocessing of microalgae do not always have access to microalgal cultivation systems to generate large amounts of fresh microalgal biomass. Using resuspended freeze-dried microalgal biomass as a model laboratory system for concentrated fresh biomass during cell disruption experiments offers greater flexibility in experimental planning and omits investment costs of microalgal cultivation equipment. So far, it however remains unclear whether freeze-dried resuspended biomass can be used as a model laboratory system to represent concentrated fresh biomass during cell disruption and lipid extraction experiments. This paper thus evaluated the suitability of resuspended freeze-dried Nannochloropsis as a model laboratory system for concentrated fresh Nannochloropsis during cell disruption. Ultrasound assisted cell disruption was used as example cell disruption technique and lipid extraction efficiency and free fatty acid content were investigated. Tap water and 3% sodium chloride are both suitable resuspension media for the resuspension of freeze-dried Nannochloropsis. Resuspension duration should be limited (< 120 min) to prevent the formation of free fatty acids. The condition of the biomass (concentrated fresh, or resuspended freeze-dried) prior to ultrasound assisted cell disruption did not influence the resulting lipid extraction efficiency. Resuspended freeze-dried Nannochloropsis biomass in tap water or 3% sodium chloride can thus be used as a model laboratory system for fresh microalgal biomass during research on ultrasound assisted lipid extraction. The generalization of the results to other cultivation conditions, cell disruption techniques, components of interest or microalgal species should be carefully assessed. [ABSTRACT FROM AUTHOR]

To investigate the plasma shielding of laser-induced cavitation bubbles near a wall, a pulsed laser with different energies was selected to induce cavitation bubbles on the surface of 7050-T7451 aluminum alloy. A high-speed camera captured the evolution of the cavitation bubble, while a fiber-optic hydrophone system collected the acoustic signals during the evolution. Finally, a confocal microscope was used to view and analyze the surface morphology of 7050 aluminum alloy. The experimental results indicate that as the laser energy increases, the diameter, the evolution time, the pressure of the bubble, and both the pit diameter and depth all increase. Beyond an energy level of 1.4 J, the maximum diameter and the evolution time of the laser-induced cavitation bubble begin to decrease; the maximum diameter decreases by 2.04%, and the first evolution time decreases by 3.26%. Plasma shielding was observed in this experiment. Considering that the essence of a laser-induced cavitation bubble is the interaction between a high-energy laser and a liquid medium, the abnormal decrease in the maximum diameter, evolution time, and sound pressure epitomizes the manifestation of plasma shielding. [ABSTRACT FROM AUTHOR]

As a non-invasive tool, ultrasound waves can be applied to probe gaseous content of the drilling fluid in offshore oil-drilling operations. The approach is believed to improve sensitivity and accuracy of a gas-kick detection system. In this research, four types of bubble flow are designed to simulate undeveloped gas kicks, and their effects on changes of ultrasound waves are investigated. The bubbles are found to have changed power distribution of the sound waves that have been reflected by the bubbles and received by side sensors. The pattern of power spectrum changes around the master frequency is found to be closely related to the type of bubble flow. Such changes are grouped on the basis of cluster analysis, and it is found that bubble strings and bubble groups would produce substantially different effects and that bubble mergences would largely alter spectral property of the sound waves. By establishing relationship between power-change pattern of sound waves and the behavior of a bubble flow, the research is intended to seek a more predictive way of recognizing early-stage gas kicks for offshore oil-drilling practices. [ABSTRACT FROM AUTHOR]

Currently, the majority of research on double cavitation bubbles focuses on horizontally arranged structures, while investigations into the pulsation of vertically aligned double bubbles remain limited. This paper aims to conduct high-speed photography research on the interaction of vertically structured double cavitation bubbles induced by pulsed laser. The pulsed laser induced cavitation method is used to induce the formation of vertically arranged double cavitation bubbles, and high-speed photography techniques are employed to investigate their pulsation characteristics.The double cavitation bubbles studied are divided into three forms according to the initial size ratio S*. The results indicate that, for vertically arranged double cavitation bubbles, similar-sized bubbles 1 ≤ S * < 1.15 exhibit mutual attraction and fusion, with a tendency for fusion preceding separation. Bubbles of different sizes 1.15 ≤ S * < 3 repel during the expansion process and attract during the shrinkage process.The pulsation of small bubbles with extremely different sizes S * ≥ 3 is strongly influenced by repulsion, while the pulsation of large bubbles is essentially unaffected. [ABSTRACT FROM AUTHOR]

Radiotherapy treatment plans have become highly conformal, posing additional constraints on the accuracy of treatment delivery. Here, we explore the use of radiation-sensitive ultrasound contrast agents (superheated phase-change nanodroplets) as dosimetric radiation sensors. In a series of experiments, we irradiated perfluorobutane nanodroplets dispersed in gel phantoms at various temperatures and assessed the radiation-induced nanodroplet vaporization events using offline or online ultrasound imaging. At 25 °C and 37 °C, the nanodroplet response was only present at higher photon energies (≥10 MV) and limited to <2 vaporization events per cm2 per Gy. A strong response (~2000 vaporizations per cm2 per Gy) was observed at 65 °C, suggesting radiation-induced nucleation of the droplet core at a sufficiently high degree of superheat. These results emphasize the need for alternative nanodroplet formulations, with a more volatile perfluorocarbon core, to enable in vivo photon dosimetry. The current nanodroplet formulation carries potential as an innovative gel dosimeter if an appropriate gel matrix can be found to ensure reproducibility. Eventually, the proposed technology might unlock unprecedented temporal and spatial resolution in image-based dosimetry, thanks to the combination of high-frame-rate ultrasound imaging and the detection of individual vaporization events, thereby addressing some of the burning challenges of new radiotherapy innovations. [ABSTRACT FROM AUTHOR]