Deciphering the hydrodynamics of lipid-coated microbubble sonoluminescence for sonodynamic therapy.

Sonodynamic therapy (SDT) is a minimally invasive targeted cancer therapy that uses focused low-intensity ultrasound (<10 MPa, <10 W/cm2) to activate sonosensitizer drugs. Once activated, these chemical compounds generate reactive oxygen species (ROS) to damage and kill cancer cells. A Phase I clinical trial has shown promising results for treating glioblastoma with SDT. We hypothesize that the efficacy of SDT can be improved by introducing lipid-coated microbubbles that produce a sonochemical effect that enhances ROS production. We investigate the hydrodynamics of a U.S. Food and Drug Administration (FDA)-approved microbubble, Lumason®, and a phospholipid-coated oxygen microbubble to predict the ultrasound parameters that induce sonoluminescence onset in biophysically relevant medium (e.g., water and blood) under clinical SDT conditions. The threshold pressures and frequencies for sonoluminescence with these therapeutic agents lie between 20 kHz - 1 MHz and 0.05 MPa - 1 MPa, respectively. The lipid-coated oxygen microbubble exhibits stronger sonoluminescence than the Lumason® microbubble, suggesting its use for improving SDT efficacy.

CMUT for ultrafast passive cavitation detection during ultrasound-induced blood-brain barrier disruption: proof of concept study.

OBJECTIVE: Cavitation dose monitoring plays a key role in ultrasound drug delivery to the brain. The use of CMUT technology has a great potential for passive cavitation detection (PCD). Approach. Here, a circular (diameter 7mm) capacitive micromachined ultrasonic transducer (CMUT) centered at 5MHz was designed to be inserted into a therapeutic transducer (1.5MHz) used for ultrasound-induced blood-brain barrier (BBB) disruption on mice. CMUT-based real-time cavitation detection was performed during the ultrasound procedure (50µL intravenous injection of SonoVue microbubbles, Frequency 1.5MHz, PNP 480kPa, Duty Cycle 10%, PRF 10Hz, Duration 60s). BBB disruption were confirmed by contrast-enhanced 7T-MRI. Main results. The CMUT device has a fractional bandwidth of 140%, almost twice a conventional piezocomposite PCD transducer. As expected, the CMUT device was able to detect the occurrence of harmonic, subharmonic and ultraharmonic frequencies as well as the increase of broadband signal indicating inertial cavitation in a wide frequency range (from 0.75 to 6 MHz). Signal-to-noise ratio was high enough (> 40 dB) to perform ultrafast monitoring and follow the subtle intrapulse variations of frequency components at a rate of 10 kHz. Significance. This first in vivo proof of concept demonstrates the interest of CMUT for PCD and encourages us to develop devices for PCD in larger animals by integrating an amplifier directly to the CMUT front-end to considerably increase the signal-to-noise ratio.

Sonothrombolysis Using Microfluidically Produced Microbubbles in a Murine Model of Deep Vein Thrombosis.

The need for safe and effective methods to manage deep vein thrombosis (DVT), given the risks associated with anticoagulants and thrombolytic agents, motivated research into innovative approaches to resolve blood clots. In response to this challenge, sonothrombolysis is being explored as a technique that combines microbubbles, ultrasound, and thrombolytic agents to facilitate the aggressive dissolution of thrombi. Prior studies have indicated that relatively large microbubbles accelerate the dissolution process, either in an in vitro or an arterial model. However, sonothrombolysis using large microbubbles must be evaluated in venous thromboembolism diseases, where blood flow velocity is not comparable. In this study, the efficacy of sonothrombolysis was validated in a murine model of pre-existing DVT. During therapy, microfluidically produced microbubbles of 18 µm diameter and recombinant tissue plasminogen activator (rt-PA) were administered through a tail vein catheter for 30 min, while ultrasound was applied to the abdominal region of the mice. Three-dimensional ultrasound scans were performed before and after therapy for quantification. The residual volume of the thrombi was 20% in animals post sonothrombolysis versus 52% without therapy ( p = 0.012 < 0.05 ), indicating a significant reduction in DVT volume. Histological analysis of tissue sections confirmed a reduction in DVT volume post-therapy. Therefore, large microbubbles generated from a microfluidic device show promise in ultrasound-assisted therapy to address concerns related to venous thromboembolism.

Application of microbubble air flotation to harvest Microcystis sp. from agriculture wastewater: The regulation and mechanisms.

The harvesting of microalgae is the main bottleneck of its large-scale biomass production, and seeking an efficient, green, and low-cost microalgae harvesting technology is one of the urgent problems to be solved. Microbubble air flotation has been proven to be an effective measure, but the mechanisms of microbubbles-algal cell attachment are still unclear. In this study, microbubble air flotation was used as a harvesting method for Microcystis cultured in agricultural wastewater. The process mechanism of microbubble air flotation harvesting microalgae in wastewater was fully revealed from three aspects (the design of bubble formation, the adhesion law, and the recovery rate of microalgae under different working conditions). The results show that the length of the release pipe is the main factor affecting the proportion of microbubbles with a particle size of less than 50 µm. In the process of adhesion, when the particle size of microbubbles is 0.6-1.7 times the size of Microcystis, the adhesion efficiency of microbubbles to Microcystis is the highest. Under the conditions of pressure 0.45 MPa, gas-liquid ratio 5%, and release pipe length 100 cm, the harvesting performance of Microcystis was the best. Microbubble air flotation has better harvesting performance (63.5%, collection rate) of Microcystis with higher density. By understanding the mechanism of microbubble flotation, the technical parameters of microbubble flotation for harvesting energy microalgae are optimized to provide support for the development of efficient and low-cost devices and equipment for collecting microalgae.

Vessel recovery using ultrasound localisation microscopy: An in silico comparative study between minimum variance and delay-and-sum beamformers.

The use of particle localisation and tracking algorithms on Contrast Enhanced Ultrasound (CEUS) or other ultrasound mode image data containing sparse microbubble (MB) populations, can produce super-resolved vascularization maps. Typically such data stem from conventional delay and sum (DAS) beamforming that is used widely in ultrasound imaging modes. Recently, adaptive beamforming has shown significant improvement in spatial resolution, but its value to super-resolution image analysis approaches is not fully understood. The in silico study here evaluates the performance of combining minimum variance beamformers (MV BF), established to provide improved lateral resolution, compared to DAS BFs with single particle detection. The isolated effect of a range of simplified image-affecting factors such as flow profile, pulse length, noise, vessel separations and data availability is considered. The study aims to assess the vessel recovery performance using the different beamformers and investigate the link with MB detection and localisation. The MV BF was shown to provide improved microvessel position accuracy compared to conventional DAS BFs. In particular, vessel separations between 0.3-4 λ provided superior localisation uncertainty with the MV. In addition, for a separation of 0.36λ, vessel recovery was achieved with both methods but the use of MV eliminated artifacts that appear as additional vessels. These results were found to be linked to improved MB detection and localisation for the MV BF, which is proposed as suitable for testing in Ultrasound Localisation Microscopy (ULM) imaging using patient data.

Ultrasound targeted microbubble destruction assisted exosomal delivery of siHmox1 effectively inhibits doxorubicin-induced cardiomyocyte ferroptosis.

Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-regulation of Hmox1, as knockdown of Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery of siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed by ultrasound microbubble targeted destruction (UTMD) in the heart region. UTMD greatly facilitated exosome delivery into heart. Consistently, UTMD assisted exosomal delivery of siHomox1 nearly blocked the ferroptosis and the subsequent cardiotoxicity induced by doxorubicin. In summary, our findings reveal that the upregulation of HMOX1 induces ferroptosis in cardiomyocytes and UTMD-assisted exosomal delivery of siHmox1 can be used as a potential therapeutic strategy for DIC.

Macrophage uptake rate of Sonazoid in breast lymphosonography is highly conserved in healthy controls.

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-1and 0.4 ± 0.1 h-1for relative lymphatic flow (EFl) andki, respectively. Furthermore, the roughly 25% sd of thekimeasurement was similar to the sd that would be expected from realistic noise simulations for a stable 0.4 h-1value ofki, suggesting that macrophage concentration is highly consistent among cancer-free SLNs. These results, along with the significantly smaller variance inkimeasurement observed compared to relative lymphatic flow suggest thatkimay 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.

Low-intensity focused ultrasound combined with microbubbles for non-invasive downregulation of rabbit carotid body activity in the treatment of hypertension.

Targeting the carotid body (CB) is a new approach in treating hypertension. This study investigates the efficacy and safety of ultrasound combined with microbubbles in targeting CB to treat hypertension. Twenty-seven hypertensive rabbits were randomly assigned to three groups: microbubbles only (sham group, n = 11), ultrasound plus microbubbles (LIFU group, n = 11), and bilateral carotid sinus nerve denervation (CSND group, n = 5). Four weeks post-intervention, blood pressure, hypoxic ventilatory response (HVR), blood pressure variability (BPV), heart rate variability (HRV), biochemical indicators, neurohormones, and histopathology were assessed in all groups. The results indicated significant reductions in systolic and diastolic blood pressure in the LIFU and CSND groups post-intervention, along with decreases in BPV, HRV, and catecholamines. HVR results showed a 35.10% reduction in CB activity in the LIFU group compared to the sham group, which was significantly lower than the reduction in the CSND group compared to the sham group (73.85%). Histopathology and transmission electron microscopy confirmed CB damage and cell apoptosis, with immunofluorescence showing a reduction in type I and II cells. In conclusion, LIFU combined with microbubbles can reduce blood pressure by lowering CB and sympathetic nerve activity.

Functionalization of microbubbles in a microfluidic chip for biosensing application.

Microbubbles are widely used for biomedical applications, ranging from imagery to therapy. In these applications, microbubbles can be functionalized to allow targeted drug delivery or imaging of the human body. However, functionalization of the microbubbles is quite difficult, due to the unstable nature of the gas/liquid interface. In this paper, we describe a simple protocol for rapid functionalization of microbubbles and show how to use them inside a microfluidic chip to develop a novel type of biosensor. The microbubbles are functionalized with biochemical ligand directly at their generation inside the microfluidic chip using a DSPE-PEG-Biotin phospholipid. The microbubbles are then organized inside a chamber before injecting the fluid with the bioanalyte of interest through the static bubbles network. In this proof-of-concept demonstration, we use streptavidin as the bioanalyte of interest. Both functionalization and capture are assessed using fluorescent microscopy thanks to fluorescent labeled chemicals. The main advantages of the proposed technique compared to classical ligand based biosensor using solid surface is its ability to rapidly regenerate the functionalized surface, with the complete functionalization/capture/measurement cycle taking less than 10 min.

Quantitative evaluation of anti-biofilm cavitation activity seeded from microbubbles or protein cavitation nuclei by passive acoustic mapping.

OBJECTIVE: Bacterial biofilms represent a major challenge for effective antibiotic therapy as they confer physical and functional changes that protect bacteria from their surrounding environment. In this work, focused ultrasound in combination with cavitation nuclei was used to disrupt biofilms of Staphylococcus aureus and Pseudomonas aeruginosa, both of which are on the World Health Organization's priority list for new antimicrobial research. Approach: Single species biofilms were exposed to ultrasound (0.5 MHz centre frequency, 0.5-1.5 MPa peak rarefactional pressure, 200 cycle pulses, 5 Hz repetition frequency, 30 s duration), in the presence of two different types of cavitation nuclei. Quantitative passive acoustic mapping (PAM) was used to monitor cavitation emissions during treatment using a calibrated linear array. Main Results: It was observed that the cumulative energy of acoustic emissions during treatment was positively correlated with biofilm disruption, with differences between bacterial species attributed to differences in biofilm morphology. PCaN provided increased biofilm reduction compared to microbubbles due in large part to their persistence over the duration of ultrasound exposure. There was also good correlation between the spatial distribution of cavitation as characterized by PAM and the extent of biofilm disruption observed with microscopy. Significance: Collectively, the results from this work indicate the potential broad applicability of cavitation for eliminating biofilms of priority pathogens and the opportunity presented by Passive Acoustic Mapping for real-time monitoring of antimicrobial processes.

Bibliometric and visualized analysis of ultrasound combined with microbubble therapy technology from 2009 to 2023.

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.

Soft Memristor at a Microbubble Interface.

Memristors show promising features for neuromorphic computing. Here we report a soft memristor based on the liquid-vapor surface of a microbubble. The thickness of the liquid film was modulated by electrostatic and interfacial forces, enabling resistance switches. We found a pinched current hysteresis at scanning periods between 1.6 and 51.2 s, while representing a resistor below 1.6 s and a diode-like behavior above 51.2 s. We approximate the thickening/thinning dynamics of liquid film by pressure-driven flow at the interface and derived the impacts of salt concentration and voltage amplitude on the memory effects. Our work opens a new approach to building nanofluidic memristors by a soft interface, which may be useful for new types of neuromorphic computing in the future.

Exogenous microbubbles contribute to valorization of microalgal compounds by ultrasound-assisted extraction.

Ultrasound-assisted extraction (UAE) shows great potential in exploiting microalgal compounds. However, upgrading the extraction system lacks concerns. This study proposes a novel sono-reactor featuring a microbubble distributor for increasing bubble abundance and correspondingly improving microalgal compound extraction. Results indicate that protein concentrations increase with ultrasound powers and extraction time while an optimized gas flow rate exists. The optimal parameters by Box-Behnken design are power 646.0 W, nitrogen flow rate 25.0 mL/min, and time 40.0 min, with an optimal protein concentration of 249.1 mg/L - a substantial improvement over gas-free extraction. The strategic increase in bubble abundance enhances microalgal compound extraction efficiency and extraction kinetics. The system innovation will contribute to the advancement of bioresource utilization and sustainability.

International cross-sectional survey on attitudes and practices regarding use of contrast-enhanced ULTRAsound in VASCular surgery: The I-ULTRA-VASC study.

OBJECTIVES: The aim of this cross-sectional survey was to gather attitudes and practices of physicians from different countries regarding the implementation of contrast-enhanced ULTRAsound (CEUS) for vascular diseases in clinical practice as well as in academic research. METHODS: A web-based survey was developed in English, including 35 questions. Two-hundred sixty physicians were invited by email to fill in the survey anonymously on Google Forms using a dedicated link. The survey started on 25th February 2024 and was closed on 13th March 2024 (17 days). A reminder was sent after the first 10 days. In addition to descriptive statistics, sub-analyses of answers according to country of origin (Italy vs other States), years of experience (≤20 years vs > 20 years), and type of institution (Academic/University vs Non-Academic/Private) were also established a priori. RESULTS: A total of 121 practitioners from 20 countries completed our survey (response rate 121/260, 46%). Most responders were males (95/121, 78.5%). Most participants were vascular surgeons (118/121, 97.5%). CEUS was available in 87/121, 70.2% of the centers involved, even though a standardized protocol was present in 54/121, and 44% of surveyed institutions. Italian institutions presented greater CEUS availability (62/72, 86.1% vs 25/49, 51.0%; p = .001) and higher presence of standardized protocols (38/72, 52.8% vs 16/49, 32.6%; p = .022) than foreign institutions. The diagnostic tool was thought to be more useful for carotid artery stenosis in the postoperative phase, while for abdominal aortic aneurysms (AAAs) in the preoperative phase. For diagnosis and/or preoperative management of carotid stenosis 53/121, 44% of physicians believed that CEUS should be performed only in selected cases, while for AAA 42/121, 35% of them believed that it could be useful only for scientific purposes. Similarly, 99/121, 82% of participants answered that CEUS was usually prescribed in 0%-20% of the cases during the preoperative diagnostic pathway of patients with peripheral arterial disease. No differences between country of origin, years of experience, and type of institution were found for the reported items. There was also 106/121, 88% of respondents agreed upon the need for better integration of CEUS in current guidelines and 114/121, 94% of them upon the need for further studies. CONCLUSIONS: This ULTRA-VASC survey has demonstrated that CEUS is still rarely used in current practice for many vascular diseases despite the availability of this tool in most centers Future studies are needed, as well as enhanced guidance on the proper implementation of CEUS from guidelines.

Focused ultrasound therapy for Alzheimer's disease: exploring the potential for targeted amyloid disaggregation.

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 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. 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.

Ultrasound Combination to Improve the Efficacy of Current Boron Neutron Capture Therapy for Head and Neck Cancer.

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.

Comparison of the diagnostic performance of contrast-enhanced ultrasound and high-resolution magnetic resonance imaging in the evaluation of histologically defined vulnerable carotid plaque: a systematic review and meta-analysis.

Background: Vulnerable carotid plaque is closely associated with ischemic stroke. Contrast-enhanced ultrasound (CEUS) and high-resolution magnetic resonance imaging (HR-MRI) are two imaging modalities capable of assessing the vulnerability of carotid plaques. This systematic review aimed to compare the diagnostic performance of CEUS and HR-MRI in the evaluation of histologically defined vulnerable carotid plaques. Methods: A systematic literature search with predefined search terms was performed on PubMed, the Cochrane library, Embase, and Web of Science from January 2001 to December 2023. Studies that evaluated the diagnostic accuracy of vulnerable carotid plaques confirmed by histology with CEUS and/or HR-MRI were included. The pooled values were calculated using a random-effects meta-analysis to determine diagnostic power. Results: This analysis included a total of 839 patients from 20 studies comprising 1,357 HR-MRI plaques and CEUS 504 plaques. With the reference to histological results, all nine CEUS studies focused on the detection of intraplaque neovascularization (IPN), and three studies also examined morphological changes or ulcerated plaques; meanwhile, among the HR-MRI studies, seven predominantly focused on identifying intraplaque hemorrhage (IPH) and three mainly examined lipid-rich necrotic cores (LRNCs). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the curve (AUC) for CEUS studies were 0.85 [95% confidence interval (CI): 0.81-0.89], 0.76 (95% CI: 0.69-0.83), 3.41 (95% CI: 1.68-6.94), 0.14 (95% CI: 0.05-0.38), 27.68 (95% CI: 5.78-132.62), and 0.89 [standard error (SE) 0.06], respectively; for HR-MRI, these values were 0.88 (95% CI: 0.85-0.90), 0.89 (95% CI: 0.86-0.92), 7.49 (95% CI: 3.28-17.09), 0.17 (95% CI: 0.12-0.24), 49.13 (95% CI: 23.87-101.11), and 0.94 (SE 0.01), respectively. The difference in AUC between the two modalities was not statistically significant (Z=0.82; P=0.68). Conclusions: CEUS and HR-MRI are valuable noninvasive diagnostic tools for identifying histologically confirmed vulnerable carotid plaques and demonstrate similar diagnostic performance. CEUS is more capable of detecting IPN and morphological changes, while HR-MRI is more suited to classifying IPH and LRNCs.

Ultrasound-stimulated microbubbles enhances radiosensitivity in cervical cancer.

BACKGROUND: Ultrasound-stimulated microbubble (USMB) therapy has proven efficacy of targeting tumor vasculature and enhancing the effect of radiation in tumor xenografts. In this investigation, we studied whether this treatment enhances the sensitivity of cervical cancer to radiation. METHODS: Human cervical cancer (ME-180 and SiHa) cells were treated with USMB or exposed to radiation (0, 2, 4, 6 and 8 Gy) or radiation (8 Gy) in combination with USMB. Clone formation assay and CCK-8 assay were used to analyze the proliferation capacity of cells. Apoptosis and DNA double-strand breaks were detected using flow cytometry and immunofluorescence staining of gamma-H2AX (γ-H2AX), respectively. Matrigel tubule formation was performed to evaluate the angiogenesis of human umbilical vein endothelial cells. In xenograft model of SiHa cells, tumor tissue expression of CD31 was detected by immunohistochemistry. RESULTS: USMB and radiation synergistically restrained the growth of ME-180 and SiHa cells. USMB promoted radiation-induced apoptosis by enhancing the levels of proapoptotic proteins. Furthermore, USMB enhanced radiation-induced γ-H2AX foci to induce DNA double-strand breaks in cervical cancer cells. USMB in combination with radiation reduced the angiogenic capacity of endothelial cells in vitro. Moreover, USMB strengthened the inhibitory effect of radiation on tumor growth and angiogenesis in xenograft models. CONCLUSION: In conclusion, USMB exposure effectively enhanced the destructive effect of radiation on cervical cancer, suggesting that USMB might be a promising sensitizer of radiotherapy to treat cervical cancer.