Low-intensity Ultrasound Research Articles

Progression in low-intensity ultrasound-induced tumor radiosensitization.

Radiotherapy (RT) is a widely utilized tumor treatment approach, while a significant obstacle in this treatment modality is the radioresistance exhibited by tumor cells. To enhance the effectiveness of RT, scientists have explored radiosensitization approaches, including the use of radiosensitizers and physical stimuli. Nevertheless, several approaches have exhibited disappointing results including adverse effects and limited efficacy. A safer and more effective method of radiosensitization involves low-intensity ultrasound (LIUS), which selectively targets tumor tissue and enhances the efficacy of radiation therapy. This review summarized the tumor radioresistance reasons and explored LIUS potential radiosensitization mechanisms. Moreover, it covered diverse LIUS application strategies in radiosensitization, including the use of LIUS alone, ultrasound-targeted intravascular microbubble destruction, ultrasound-mediated targeted radiosensitizers delivery, and sonodynamic therapy. Lastly, the review presented the limitations and prospects of employing LIUS-RT combined therapy in clinical settings, emphasizing the need to connect research findings with practical applications. LIUS employs cost-effective equipment to foster tumor radiosensitization, curtail radiation exposure, and elevate the quality of life for patients. This efficacy is attributed to LIUS's ability to utilize thermal, cavitation, and mechanical effects to overcome tumor cell resistance to RT. Multiple experimental analyses have underscored the effectiveness of LIUS in inducing tumor radiosensitization using diverse strategies. While initial studies have shown promising results, conducting more comprehensive clinical trials is crucial to confirm its safety and effectiveness in real-world situations.

Effectiveness of low-intensity ultrasound on anaerobic bioaugmentation of phenolic wastewater: Model optimization and system stabilization

The study optimized the parameters of low-intensity ultrasound (LIUS), including ultrasound density (0.25 W·mL−1), duration (12 min), and interval time (48 h), through a combination of uniform experiments and response surface prediction. The optimized parameters were aimed at enhancing the removal efficiency of phenolic wastewater to approximately 80%. Furthermore, they facilitate the production of hydrolytic gases in anaerobic digestion, resulting in methane accumulation of up to 237.3 mL·(g VS)−1. Following the long-term experiment, LIUS has been demonstrated to effectively enhance the enzyme activity of anaerobic organisms while also damaging the bacterial structure of microorganisms. However, microbiological analysis indicates that the ultrasound-induced screening mechanism effectively increases the relative abundance of dominant bacterial communities. This facilitated the removal of persistent phenolic contaminants and stabilized the balanced development of the overall anaerobic environment. These findings suggest that LIUS can enhance biological activity and improve the anaerobic treatment of phenolic wastewater.

Ultrasound-triggered three dimensional hyaluronic acid hydrogel promotes in vitro and in vivo reprogramming into induced pluripotent stem cells

Cellular reprogramming technologies have been developed with different physicochemical factors to improve the reprogramming efficiencies of induced pluripotent stem cells (iPSCs). Ultrasound is a clinically applied noncontact biophysical factor known for regulating various cellular behaviors but remains uninvestigated for cellular reprogramming. Here, we present a new reprogramming strategy using low-intensity ultrasound (LIUS) to improve cellular reprogramming of iPSCs in vitro and in vivo. Under 3D microenvironment conditions, increased LIUS stimulation shows enhanced cellular reprogramming of the iPSCs. The cellular reprogramming process facilitated by LIUS is accompanied by increased mesenchymal to epithelial transition and histone modification. LIUS stimulation transiently modulates the cytoskeletal rearrangement, along with increased membrane fluidity and mobility to increase HA/CD44 interactions. Furthermore, LIUS stimulation with HA hydrogel can be utilized in application of both human cells and in vivo environment, for enhanced reprogrammed cells into iPSCs. Thus, LIUS stimulation with a combinatorial 3D microenvironment system can improve cellular reprogramming in vitro and in vivo environments, which can be applied in various biomedical fields.

Towards an understanding of the mechanisms of therapeutic ultrasound on biomimetic models of cancer

Therapeutic ultrasound is transforming the treatment of a range of malignancies in a non-invasive and non-systemic manner. Low-intensity ultrasound (LIUS) has been proposed to selectively eradicate cancer cells but the underlying biological mechanisms remains unknown. To gain an understanding of this phenomenon, 2D breast cancer monocultures were sonicated at varying acoustic intensities (0.1–0.5 W·cm−2) and excitation times (1–10 minutes). Additionally, 2D monocultures consisting of healthy cell lines were sonicated at varying acoustic intensities (0.1–0.5 W·cm−2) to determine any distinguishing biological responses. To begin recapitulating in vivo conditions, breast cancer cells were also seeded into 3D collagen hydrogels. At a 1 MHz frequency, 20% duty cycle, 100 Hz pulse repetition frequency, a significant drop in cancer cell viability is observed at a sonication intensity of 0.5 W·cm−2 and over 10 minute excitation time. Healthy counterparts subjected to the same parameters revealed no distinguishing effects. Sonication of breast cancer cells seeded in 3D collagen hydrogels revealed no effect in cell viability compared to non-sonicated controls. The acoustic wave propagation software OptimUS was used to determine the influence culturing plates have on ultrasound propagation, revealing these materials can significantly vary the acoustic field at frequencies relevant to LIUS.

Continuous Low-Intensity Ultrasound Improves Cartilage Repair in Rabbit Model of Subchondral Injury.

Subchondral drilling (SD), a bone marrow stimulation technique, is used to repair cartilage lesions that lack regenerative potential. Cartilage repair outcomes upon SD are typically fibrocartilaginous in nature with inferior functionality. The lack of cues to foster the chondrogenic differentiation of egressed mesenchymal stromal cells upon SD can be attributed for the poor outcomes. Continuous low-intensity ultrasound (cLIUS) at 3.8 MHz is proposed as a treatment modality for improving cartilage repair outcomes upon marrow stimulation. Bilateral defects were created by SD on the femoral medial condyle of female New Zealand white rabbits (n = 12), and the left joint received cLIUS treatment (3.8 MHz, 3.5 Vpp, 8 min/application/day) and the contralateral right joint served as the control. On day 7 postsurgery, synovial fluid was aspirated, and the cytokine levels were assessed by Quantibody™ assay. Rabbits were euthanized at 8 weeks and outcomes were assessed macroscopically and histologically. Defect areas in the right joints exhibited boundaries, incomplete fill, irregular cartilage surfaces, loss of glycosaminoglycan (GAG), and absence of chondrocytes. In contrast, the repaired defect area in the joints that received cLIUS showed complete fill, positive staining for GAG with rounded chondrocyte morphology, COL2A1 staining, and columnar organization. Synovial fluid collected from cLIUS-treated left knee joints had lower levels of IL1, TNFα, and IFNγ when compared to untreated right knee joints, alluding to the potential of cLIUS to mitigate early inflammation. Further at 8 weeks, left knee joints (n = 12) consistently scored higher on the O'Driscoll scale, with a higher percent hyaline cartilage score. No adverse impact on bone or change in the joint space was noted. Upon a single exposure of cLIUS to TNFα-treated cells, nuclear localization of pNFκB and SOX9 was visualized by double immunofluorescence and the expression of markers associated with the NFκB pathway was assayed by quantitative real-time polymerase chain reaction. cLIUS extends its chondroprotective effects by titrating pNFκB levels, preventing its nuclear translocation, while maintaining the expression of SOX9, the collagen II transcription factor. Our combined results demonstrate that healing of chondral defects treated with marrow stimulation by SD can be accelerated by employing cLIUS regimen that possesses chondroinductive and chondroprotective properties. Impact statement Repair of cartilage represents an unsolved biomedical burden. In vitro, continuous low-intensity ultrasound (cLIUS) has been demonstrated to possess chondroinductive and chondroprotective potential. To our best knowledge, the use of cLIUS to improve cartilage repair outcomes upon marrow stimulation, in vivo, has not been reported and our work reported here fills that gap. Our results demonstrated enhanced cartilage repair outcomes under cLIUS (3.8 MHz) in a rabbit model of subchondral injury by subchondral drilling. Enhanced repair stemmed from mesenchymal stem cell differentiation in vivo and the subsequent synthesis of articular cartilage-specific matrix.

Correction: Effect of Low-Intensity Ultrasound on the Temperature Field and Microstructure of 2219 Aluminum Alloy

Correction: Effect of Low-Intensity Ultrasound on the Temperature Field and Microstructure of 2219 Aluminum Alloy

Effect of Low-Intensity Ultrasound on the Temperature Field and Microstructure of 2219 Aluminum Alloy

Effect of Low-Intensity Ultrasound on the Temperature Field and Microstructure of 2219 Aluminum Alloy

Rib detection using pitch-catch ultrasound and classification algorithms for a novel ultrasound therapy device

BackgroundNoninvasive ultrasound (US) has been used therapeutically for decades, with applications in tissue ablation, lithotripsy, and physical therapy. There is increasing evidence that low intensity US stimulation of organs can alter physiological and clinical outcomes for treatment of health disorders including rheumatoid arthritis and diabetes. One major translational challenge is designing portable and reliable US devices that can be used by patients in their homes, with automated features to detect rib location and aid in efficient transmission of energy to organs of interest. This feasibility study aimed to assess efficacy in rib bone detection without conventional imaging, using a single channel US pitch-catch technique integrated into an US therapy device to detect pulsed US reflections from ribs.MethodsIn 20 healthy volunteers, the location of the ribs and spleen were identified using a diagnostic US imaging system. Reflected ultrasound signals were recorded at five positions over the spleen and adjacent ribs using the therapy device. Signals were classified as between ribs (intercostal), partially over a rib, or fully over a rib using four models: threshold-based time domain classification, threshold-based frequency domain classification, logistic regression, and support vector machine (SVM).ResultsSVM performed best overall on the All Participants cohort with accuracy up to 96.25%. All models’ accuracies were improved by separating participants into two cohorts based on Body Mass Index (BMI) and re-fitting each model. After separation into Low BMI and High BMI cohorts, a simple time-thresholding approach achieved accuracies up to 100% and 93.75%, respectively.ConclusionThese results demonstrate that US reflection signal classification can accurately provide low complexity, real-time automated onboard rib detection and user feedback to advance at-home therapeutic US delivery.

Research trends on the use of ultrasound as neuromodulation-based therapy, based on bibliometric analysis

Link of Video Abstract: https://youtu.be/3g92-Hr_5c0 Introduction: Ultrasound has seen a significant increase in use in neuromodulation-based therapy over the past decade due to technological advancements, enabling precise tissue ablation, clinical neuromodulatory brain stimulation, and targeted blood-brain barrier permeabilization. The bibliometric analysis reveals a growing body of literature focused on the utilization of low-intensity ultrasound (LI-US) and high-intensity focused ultrasound (HIFUS) in the field of neuromodulation. Ultrasonography has potential applications in treating neurological and psychiatric illnesses like neuropathic pain, epilepsy, and treatment-resistant mental illness, but further investigation is needed to understand mechanisms and safety considerations. The use of bibliometric analysis can effectively identify common research patterns and highlight advancements in this specific academic field. Research indicates that ultrasound-based neuromodulation approaches may offer novel therapeutic interventions with enhanced efficacy and safety in treating various neurological and mental illnesses. Methods: The process of data collection involved conducting a search on the Scopus website using specific keywords. Subsequently, the collected data is stored in the file formats of .bib and .csv. These files are then subjected to analysis using the biblioshiny and Vosviewer software tools. The research not only use quantitative analysis but also incorporates qualitative investigations. Results: The trend of the most significant affiliations, authors, documents with the highest number of citations, relevant sources, cited nations, and annual scientific production was determined. This academic study employs many visualization techniques, including overlay visualization of the Scopus database, utilization of VOSviewer for database analysis, network visualization, density visualization, and thematic mapping. Conclusions: The use of ultrasound as a neuromodulation therapy offers numerous opportunities and potential across various sub-topics, despite a limited literature corpus compared to other academic disciplines. The use of this discipline in human subjects is limited, requiring extensive clinical studies and cross-national collaboration for the advancement of therapeutic interventions.

Effects of low-intensity ultrasound opening the blood-brain barrier on Alzheimer's disease-a mini review.

Due to the complex pathological mechanisms of Alzheimer's disease (AD), its treatment remains a challenge. One of the major difficulties in treating AD is the difficulty for drugs to cross the blood-brain barrier (BBB). Low-intensity ultrasound (LIUS) is a novel type of ultrasound with neuromodulation function. It has been widely reported that LIUS combined with intravenous injection of microbubbles (MB) can effectively, safely, and reversibly open the BBB to achieve non-invasive targeted drug delivery. However, many studies have reported that LIUS combined with MB-mediated BBB opening (LIUS + MB-BBBO) can improve pathological deposition and cognitive impairment in AD patients and mice without delivering additional drugs. This article reviews the relevant research studies on LIUS + MB-BBBO in the treatment of AD, analyzes its potential mechanisms, and summarizes relevant ultrasound parameters.

Overcome of Cisplatin Resistance in Ovarian Cancer by Combination of Low-intensity Ultrasound and Cisplatin.

Platinum-based chemotherapeutics are the main treatment options for ovarium cancer. However, the development of drug resistance is one of the major issues in chemotherapy. Even targeting a specific pathway may not produce an efficient sensitization to the chemo agent due to various pathways related to developing resistance against cisplatin. Hence, more effective strategies against drug resistance are essential for cancer treatment. In the presence of the ultrasonic waves, increased membrane porosity enables more drug uptake into the cancer cell. Therefore, the promising method in cancer therapy is seen as the use of the combined effect of chemotherapy and low-Intensity Ultrasound (LIUS) to overcome chemoresistance. The present study aimed to examine the effects of Ultrasound (US)+Cisplatin (Cis)- based combination therapy to advance an effective treatment against drug resistance in cisplatinresistant ovarian cancer cells A2780 (A2780cis) under in vitro conditions. Treatment groups as Cis and LIUS with two different ultrasound parameters (10% duty cycle (DC), 1 MHz, 1.0 W/cm2, 1 min and 50% DC, 1 MHz, 1.0 W/cm2, 3 min) were investigated to cope with the chemoresistance in A2780cis. After Cis therapy with IC50 concentrations determined in A2780 and A2780cis, drug-sensitive/resistant ovarian cancer cells were treated by ultrasound. The effects of the US+Cis combination therapy were evaluated by cell viability assays, colony formation, and cell cycle analyses. In both US parameters, the waveform was shown to be more effective in preventing drug resistance. While more than 80% of the cell population was suppressed with the US+Cis combination treatment, more than 90% of the colony formation was suppressed according to the colony formation test results. In addition, US+Cis combination therapy caused different cell cycle arrests in both A2780 and A2780cis cells. Ultrasound-based combination therapies show promising results in combating chemoresistance, and the disadvantages of conventional cancer treatments, such as cancer recurrence, drug resistance, and high cost, might reduce by the effectiveness of combination therapy of ultrasound therapy and chemotherapy.

Antibubbles Enable Tunable Payload Release with Low-Intensity Ultrasound.

The benefits of ultrasound are its ease-of-use and its ability to precisely deliver energy in opaque and complex media. However, most materials responsive to ultrasound show a weak response, requiring the use of high powers, which are associated with undesirable streaming, cavitation, or temperature rise. These effects hinder response control and may even cause damage to the medium where the ultrasound is applied. Moreover, materials that are currently in use rely on all-or-nothing effects, limiting the ability to fine-tune the response of the material on the fly. For these reasons, there is a need for materials that can respond to low intensity ultrasound with programmable responses. Here it is demonstrated that antibubbles are a low-intensity-ultrasound-responsive material system that can controllably release a payload using acoustic pressures in the kilopascal range. Varying their size and composition tunes the release pressure, and the response can be switched between a single release and stepwise release across multiple ultrasound pulses. Observations using confocal and high-speed microscopy reveal different ways that can lead to release. These findings lay the groundwork to design antibubbles that controllably respond to low-intensity ultrasound, opening a wide range of applications ranging from ultrasound-responsive material systems to carriers for targeteddelivery.

Ultrasound-Driven Healing: Unleashing the Potential of Chondrocyte-Derived Extracellular Vesicles for Chondrogenesis in Adipose-Derived Stem Cells.

Repairing cartilage defects represents a significant clinical challenge. While adipose-derived stem cell (ADSC)-based strategies hold promise for cartilage regeneration, their inherent chondrogenic potential is limited. Extracellular vesicles (EVs) derived from chondrocytes (CC-EVs) have shown potential in enhancing chondrogenesis, but their role in promoting chondrogenic differentiation of ADSCs remains poorly understood. Moreover, the clinical application of EVs faces limitations due to insufficient quantities for in vivo use, necessitating the development of effective methods for extracting significant amounts of CC-EVs. Our previous study demonstrated that low-intensity ultrasound (LIUS) stimulation enhances EV secretion from mesenchymal stem cells. Here, we identified a specific LIUS parameter for chondrocytes that increased EV secretion by 16-fold. CC-EVs were found to enhance cell activity, proliferation, migration, and 21-day chondrogenic differentiation of ADSCs in vitro, while EVs secreted by chondrocytes following LIUS stimulation (US-CC-EVs) exhibited superior efficacy. miRNA-seq revealed that US-CC-EVs were enriched in cartilage-regeneration-related miRNAs, contributing to chondrogenesis in various biological processes. In conclusion, we found that CC-EVs can enhance the chondrogenesis of ADSCs in vitro. In addition, our study introduces ultrasound-driven healing as an innovative method to enhance the quantity and quality of CC-EVs, meeting clinical demand and addressing the limited chondrogenic potential of ADSCs. The ultrasound-driven healing unleashes the potential of CC-EVs for chondrogenesis possibly through the enrichment of cartilage-regeneration-associated miRNAs in EVs, suggesting their potential role in cartilage reconstruction. These findings hold promise for advancing cartilage regeneration strategies and may pave the way for novel therapeutic interventions in regenerative medicine.

Low-intensity ultrasound combined with arsenic trioxide induced apoptosis of glioma via EGFR/AKT/mTOR

AimsThis study aimed to explore whether low-intensity ultrasound (LIUS) combined with low-concentration arsenic trioxide (ATO) could inhibit the proliferation of glioma and, if so, to clarify the potential mechanism. Main methodsThe effects of ATO and LIUS alone or in combination on glioma were examined by CCK8, EdU, and flow cytometry assays. Western blot analysis was used to detect changes in expression of apoptosis-related proteins and their effects on the EGFR/AKT/mTOR pathway. The effects of ATO and LIUS were verified in vivo in orthotopic xenograft models, and tumor size, arsenic content in brain tissue, survival, and immunohistochemical changes were observed. Key findingsLIUS enhanced the inhibitory effect of ATO on the proliferation of glioma, and EGF reversed the proliferation inhibition and protein changes induced by ATO and LIUS. The anti-glioma effect of ATO combined with LIUS was related to downstream AKT/mTOR pathway changes caused by inhibition of EGFR activation, which enhanced apoptosis of U87MG and U373 cells. In vivo experiments showed significant increases in arsenic content in brain tissue, as well as decreased tumor sizes and longer survival times in the combined treatment group compared with other groups. The trends of immunohistochemical protein changes were consistent with the in vitro results. SignificanceThis study showed that LIUS enables ATO to exert anti-glioma effects at a safe dose by inhibiting the activation of EGFR and the downstream AKT/mTOR pathway to regulate apoptosis. LIUS in combination with ATO is a promising novel method for treating glioma and could improve patient prognosis.

Anti-inflammatory Effect of Low-Intensity Ultrasound in Septic Rats.

Sepsis is a severe systemic inflammatory response caused by infection. Here, the spleen region of Sprague-Dawley (SD) rats with sepsis was irradiated with low-intensity ultrasound (LIUS) to explore the regulation of inflammation and its mechanism by LIUS. In this study, 30 rats used for survival analysis were randomly divided into the sham-operated group (Sham, n=10), the group in which sepsis was induced by cecal ligation and puncture (CLP, n=10) and the group treated with LIUS immediately after CLP (LIUS, n=10). The other 120 rats were randomly divided into the aforementioned three groups for detection at each time point. The parameters used in the LIUS group were 200 mW/cm2, 0.37 MHz, 20% duty cycle and 20 min, and no ultrasonic energy was produced in the Sham and CLP groups. Seven-day survival rate, histopathology and expression of inflammatory factors and proteins were evaluated in the three groups. LIUS was able to improve the survival rate of septic SD rats (p < 0.05), significantly inhibit the expression of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6) and nuclear factor-κB p65 (NF-κB p65) (p < 0.05) and restore the ultrastructure of the spleen. Our study determined that LIUS can relieve spleen damage and alleviate severe cytokine storm to improve survival outcomes in septic SD rats, and its mechanism may be related to the inhibition of the NF-κB signaling pathway by downregulation of IL-1β.

Low-Intensity Pulsed Ultrasound Neuromodulation of a Rodent's Spinal Cord Suppresses Motor Evoked Potentials.

Here we investigate the ability of low-intensity ultrasound (LIUS) applied to the spinal cord to modulate the transmission of motor signals. Male adult Sprague-Dawley rats (n = 10, 250-300 g, 15 weeks old) were used in this study. Anesthesia was initially induced with 2% isoflurane carried by oxygen at 4 L/min via a nose cone. Cranial, upper extremity, and lower extremity electrodes were placed. A thoracic laminectomy was performed to expose the spinal cord at the T11 and T12 vertebral levels. A LIUS transducer was coupled to the exposed spinal cord, and motor evoked potentials (MEPs) were acquired each minute for either 5- or 10-minutes of sonication. Following the sonication period, the ultrasound was turned off and post-sonication MEPs were acquired for an additional 5 minutes. Hindlimb MEP amplitude significantly decreased during sonication in both the 5- (p < 0.001) and 10-min (p = 0.004) cohorts with a corresponding gradual recovery to baseline. Forelimb MEP amplitude did not demonstrate any statistically significant changes during sonication in either the 5- (p = 0.46) or 10-min (p = 0.80) trials. LIUS applied to the spinal cord suppresses MEP signals caudal to the site of sonication, with recovery of MEPs to baseline after sonication. LIUS can suppress motor signals in the spinal cord and may be useful in treating movement disorders driven by excessive excitation of spinal neurons.

Biomechanical Response of Cancer Stem Cells to Low-intensity Ultrasound.

The presence of stem cells in cancer may increase the chances of drug resistance and invasiveness. Low-intensity ultrasound (LIUS) can regulate the biological and mechanical properties of cells and participate in cellular migration and differentiation. Although LIUS has shown significant potential in cancer treatment, the effects of LIUS on migration and drug resistance of cancer stem cells (CSCs) have remained less understanding on an angle of biomechanical. Hence, the objective of this work is to analyze the biomechanical response of LIUS to CSCs. In this study, we selected human ovarian cancer cell line A2780 and ovarian cancer stem cells (OCSCs) were enriched from A2780 cells, and observed that OCSCs had higher drug sensitivity and lower invasiveness than A2780 cells after LIUS exposure. Furthermore, we further analyzed the changes in cell morphology, cytoskeleton, and membrane stiffness of A2780 cells and OCSCs at various intensities of LIUS, these results showed that LIUS could induce morphological changes, F-actin formation and increase membrane stiffness, which could help to suppress migration and reduce the drug resistance of OCSCs. Our findings will help establish a better understanding of the biomechanical response to LIUS in CSCs, and future studies on cancer will benefit from the careful consideration of the cellular response of CSCs to LIUS stimulation, ultimately allowing for the development of more effective therapies.

A Bibliometric Analysis for Low-Intensity Ultrasound Study Over the Past Three Decades.

Low-intensity ultrasound (LI-US) is a non-invasive stimulation technique that has emerged in recent years and has been shown to have positive effects on neuromodulation, fracture healing, inflammation improvement, and metabolic regulation. This study reports the conclusions of a bibliometric analysis of LI-US. Input data for the period between 1995 and 2022, including 7209 related articles in the field of LI-US, were collected from the core library of the Web of Science (WOS) database. Using these data, a set of bibliometric indicators was obtained to gain knowledge on different aspects: global production, research areas, and sources analysis, contributions of countries and institutions, author analysis, citation analysis, and keyword analysis. This study combined the data analysis capabilities provided by the WOS database, making use of two bibliometric software tools: R software and VOS viewer to achieve analysis and data exploration visualization, and predicted the further development trends of LI-US. It turns out that the United States and China are co-leaders while Zhang ZG is the most significant author in LI-US. In the future, the hot spots of LI-US will continue to focus on parameter research, mechanism discussion, safety regulations, and neuromodulation applications.

Low-Intensity Ultrasound Reduces Brain Infarct Size by Upregulating Phosphorylated Endothelial Nitric Oxide in Mouse Model of Middle Cerebral Artery Occlusion.

There have been attempts to use therapeutic ultrasound (US) for the treatment of both experimental and clinical stroke. We hypothesized that low-intensity US has direct beneficial effects on the brain independent of cerebral blood flow (CBF) during middle cerebral artery occlusion (MCAO). Three groups of mice were studied. Group I included 84 mice with MCAO undergoing US treatment/no treatment at two US frequencies (0.25 and 1.05 MHz) with three different acoustic pressures at each frequency in which infarct size (IS) was measured 24 h later. Group II included 11 mice undergoing treatment based on best US results from group I animals in which the IS/risk area (RA) ratio was measured 24 h later. Group III included 38 normal mice undergoing US treatment/no treatment for assessment of CBF, tissue metabolite and protein expression and histopathology. Ultrasound at both frequencies and most acoustic pressures resulted in reduction in IS in group I animals, with the best results obtained with 0.25 MHz at 2.0 MPa: IS was reduced 4-fold in the cerebral cortex, 1.5-fold in the caudate putamen and 3.5-fold in the cerebral hemisphere compared with control. US application in group III animals elicited only a marginal increase in CBF despite a 2.6-fold increase in phosphorylated endothelial nitric oxide synthase (p-eNOS)-S1177 and a corresponding decrease in p-eNOS-T494. Histopathology revealed no evidence of hemorrhage, inflammation or necrosis. Low-intensity US at specific frequencies and acoustic pressures results in marked neuroprotection in a mouse model of stroke by modulation of p-eNOS independent of its effect on CBF.

Effect of Low-intensity Ultrasound on Cd Tolerance of Partial Nitrification Sludge

Cadmium (Cd) is a typical nitrification inhibitor, which has a strong inhibitory effect on partial nitrification (PN). The discrepancy on Cd tolerance of PN sludge caused by low-intensity ultrasound (LIU) was studied. It suggested that the half inhibitory concentration (IC50) of sludge was increased from 24.51 to 29.07 mg/L by 35 days of ultrasonic treatment, and the Cd tolerance of sludge was enhanced. Further analysis indicated that contents of extracellular polymeric substances (EPS) rose substantially because of LIU, which played a catalytic role on increasing adsorption capacity of PN sludge for Cd.