Non-chemical CO_(2) microbubbles as a mobility control technology in enhanced oil recovery(EOR)and carbon sequestration are becoming attractive.In this study,the EOR mechanisms of non-chemical CO_(2) microbubble(MB)in...Non-chemical CO_(2) microbubbles as a mobility control technology in enhanced oil recovery(EOR)and carbon sequestration are becoming attractive.In this study,the EOR mechanisms of non-chemical CO_(2) microbubble(MB)in low permeability reservoirs are experimentally investigated by the nuclear magnetic resonance(NMR)technology.This study reveals,for the first time,the EOR mechanisms of MB in a heterogeneous reservoir and its effect on pore structure.First,mobility reduction factors of MB with various gas–liquid ratios were determined,with MB at a gas–liquid ratio of 1 exhibiting the best performance under experimental conditions.Second,the coreflood experiments with NMR scanning were performed to reveal the EOR mechanisms of MB.It was observed that MB achieved an incremental oil recovery of 13.49% and 22.80%in the core sample with a permeability of 9.51×10^(−3) and 2.23×10^(−3)μm^(2),respectively.Benefiting from MB's conformance control,the total oil recovery was increased from 38.34%to 54.57% of original oil in place by MB in parallel core flood experiments.Third,the NMR tests demonstrated that MB significantly reduced residual oil in core samples,especially in small pore areas,which highlights the improvement of sweep efficiency by MB.Lastly,the effect of MB on pore structure was studied.The NMR tests indicated a significant increase in pore space after 1 pore volume of MB flooding.Minerals in the core sample were dissolved,leading to an increase in permeability and porosity of the core sample by 17.01%and 0.31%,respectively.Overall,the results of this study provide valuable insights into the EOR mechanisms of MB at the pore scale and offer implications for EOR and carbon sequestration in low-permeability reservoirs.展开更多
BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t...BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.展开更多
Objective:To evaluate the impact of the diameter of SonoVue microbubbles on binding characteristics, including the adhesion rate and stability, of a new contrast agent targeted to choriocarcinoma cells(JARs) in vitro,...Objective:To evaluate the impact of the diameter of SonoVue microbubbles on binding characteristics, including the adhesion rate and stability, of a new contrast agent targeted to choriocarcinoma cells(JARs) in vitro, in order to establish a foundation to explore targeted ultrasound imaging for localization of tumor cell antigens and increase the early diagnostic rate for tumors.Methods:The objects were divided into three groups:the large microbubble group(n = 15), the middling microbubble group(n = 15) and the tiny microbubble group(n = 15).The rosette formation rate was counted.JARs were calculated by flow cytometry(FCM).The targeted contrast agent was prepared by mixing SonoVue microbubbles of different diam-eter with rabbit anti-human chorionic gonadotrophin(HCG) antibody.The binding rates of the targeted contrast agent to JARs before and after PBS rinse were analyzed.Results:The binding rate was significantly lower in the large microbubble group(61.7 ± 1.8)% than in the middling microbubble group(82.6 ± 4.5)% and the tiny microbubble group(91.3 ± 5.8)%(P < 0.05).The binding rates of different diameter microbubbles to JARs before and after PBS rinse were different.The middling microbubbles were the most stable ones, with the binding rate of(82.3 ± 4.5)% and(80.4 ± 3.9)% before and after PBS rinse(P > 0.05).The binding rates of the targeted microbubbles labeled with fluorescence to JARs were 68.6%, 81.3% and 89.3% in the large microbubble group, the middling microbubble group and the tiny microbubble group, respectively(P < 0.05).Conclu-sion:The binding capacity of the targeted SonoVue microbubbles to JARs is related to the diameter of the microbubble, which is determined by the shaking method before preparation.Modulating the diameter of SonoVue microbubbles may increase the binding rate and stability of targeted microbubbles to JARs, thus to improve the image of JARs.展开更多
Objective： To explore the safety of ultrasound and microbubbles for enhancing the chemotherapeutic sensitivity of malignant tumors in the digestive system in a clinical trial, as well as its efficacy.Methods： From O...Objective： To explore the safety of ultrasound and microbubbles for enhancing the chemotherapeutic sensitivity of malignant tumors in the digestive system in a clinical trial, as well as its efficacy.Methods： From October 2014 to June 2016, twelve patients volunteered to participate in this study. Eleven patients had hepatic metastases from tumors of the digestive system, and one patient had pancreatic carcinoma. According to the mechanical index （MI） in the ultrasound field, patients were classified into four groups with MIs of 0.4, 0.6, 0.8 and 1.0. Within half an hour after chemotherapy, patients underwent ultrasound scanning with ultrasound microbubbles （SonoVue） to enhance the efficacy of chemotherapy. All adverse reactions were recorded and were classified in 4 grades according to the Common Terminology Criteria for Adverse Events version 4.03 （CTCAE V4.03）. Tumor responses were evaluated by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria. All the patients were followed up until progression.Results： All the adverse reactions recorded were level 1 or level 2. No local pain occurred in any of the patients. Among all the adverse reactions, fever might be related to the treatment with ultrasound combined with microbubbles. Six patients had stable disease （SD）, and one patient had a partial response （PR） after the first cycle of treatment. At the end of follow-up, tumor progression was restricted to the original sites, and no new lesions had appeared.Conclusions： Our preliminary data showed the potential role of a combined treatment with ultrasound and microbubbles in enhancing the chemotherapeutic sensitivity of malignant tumors of the digestive system. This technique is safe when the MI is no greater than 1.0.展开更多
Secondary radiation force can be an attractive force causing aggregates of encapsulated microbubbles in ultrasonic molecular imaging. The influence of the secondary radiation force on aggregation between two coated bu...Secondary radiation force can be an attractive force causing aggregates of encapsulated microbubbles in ultrasonic molecular imaging. The influence of the secondary radiation force on aggregation between two coated bubbles is investigated in this study. Numerical calculations are performed based on four simultaneous differential equations of radial and translational motions. Results show that the secondary force can change from attraction to repulsion during approach, and stable microbubble pairs can be formed in the vicinity of resonant regions; the possibility of microbubble aggregations can be reduced by using low exciting amplitude, ultrasonic frequencies deviating from the resonant frequencies or microbubbles with small compressibility.展开更多
The backscatter from sonicated albumin microbubbles (Albunex) was analyzed using acoustic densitometry in an in vitro pulsatile heart model to evaluate the effects of pressure on the backscatter from Albunex, and the ...The backscatter from sonicated albumin microbubbles (Albunex) was analyzed using acoustic densitometry in an in vitro pulsatile heart model to evaluate the effects of pressure on the backscatter from Albunex, and the cardiac cyclic changes of intracardiac backscatter from sonicated albumin microbubbles in 16 healthy persons were analyzed. It was found that the Albunex microbubbles were compressed in systole and decompressed in diastole, causing corresponding changes of backscatter in cardiac cycle. Although the intensities of backscatter in diastole and systole were related to the concentration of microbubbles, the concentration of microbubbles had no effect on the difference of end-diastolic and end-systolic backscatter. The difference of the backscatter was highly correlated with end-systolic pressure (r=0.96, P=0.001). In human studies, we also observed same intracardiac cyclic changes of backscatter from sonicated albumin microbubbles. Our study indicates that it is possible to evaluate the intracardiac pressure non-invasively by analyzing the intracardiac backscatter from the microbubbles with acoustic densitometry.展开更多
Objective: To investigate the role and potential mechanism of CXCR4 in promoting targeted homing of bone marrow mesenchymal stem cells(BMSCs) with ultrasound-exposed microbubbles(UM) pretreatment. Methods: Third gener...Objective: To investigate the role and potential mechanism of CXCR4 in promoting targeted homing of bone marrow mesenchymal stem cells(BMSCs) with ultrasound-exposed microbubbles(UM) pretreatment. Methods: Third generation BMSCs were divided into four groups control group, ultrasound(US) group, UM group and ultrasound-exposed microbubbles plus catalase group. RT-PCR and western blot were performed to determine the levels of CXCR4 m RNA transcription and protein expression, respectively. Third generation BMSCs were labeled with Fluo-α/AM and divided into three groups: control group, US group and UM group, and flurorescence intensities in the cells were observed immediately, 5 min and 15 min after intervention underflurorescence microscope. The calcium iron levels in the cells were analyzed. BMSCs were divided into i ve group: group A without calcium in the medium, group B, group C, group D and group E containing calcium chloride with concentration of l mol, 2 mol, 4mol, anti-calciurn-sensing receptor antibody, respectively. RT-PCR and western blot were performed to determine the levels of CXCR4 m RNA transcription and proteins expression of the third generation BMSCs of each group, respectively. Results: The levels of CXCR4 m RNA transcription and protein expression between US group and control group had no statistically signii cant dif erence(P>0.05) shown by RT-PCR and western blot; the transcription level in the UM group was signii cantly higher than that in US group and control group(P<0.05); and in the ultrasound-exposed microbubbles plus catalase group, the transcription level was much lower than that in UM group. Fluorescence intensify in the cells of US group had no signii cant dif erence compared with that in the cells of the control group(P>0.05), which in the cells of UM group was signii cantly higher than that in the cells of both US group and control group(P<0.05). Compared to group A, expressions of CXCR4 of group B to D were signii cantly increased in concentration-dependent manner showed by RT-PCR and western blot(P< 0.05). Compared to group C, expressions of CXCR4 of group E were signii cantly decreased(P< 0.05). Conclusions: UM can promote the inl ux of calcium in BMSCs and increase m RNA transcription and protein expression of CXCR4. The latter may partly be caused by influx of calcium.展开更多
Ultrasonography is an important complement to clinical diagnosis,and the application of microbubbles effectively improved diagnostic accuracy in echography.In scientific research,the sizes of microbubbles range from n...Ultrasonography is an important complement to clinical diagnosis,and the application of microbubbles effectively improved diagnostic accuracy in echography.In scientific research,the sizes of microbubbles range from nanometers to microns.By optimizing the fabrication process,bubble sizes and ultrasound parameters,microbubbles can also be used for drug delivery and therapeutic monitoring.In this review,we summarize the recent advances in the diagnosis and treatment of microbubbles according to their different components.Modification of microbubble shells allows for more accurate imaging and detection and the combined utilization of US-targeted MB destruction(UTMD)allows for non-invasive,precise and targeted delivery of drug molecules to pathological tissues.These features pave the way for the emerge of theranostic microbubbles by combination of functional compositions and the application of multifunctional materials.Theranostic microbubbles allow for the simultaneous process of diagnosis,visualization of drug delivery and therapeutic monitoring.Ultimately,theranostic microbubbles are promising in clinical practice and would enhance contrast-enhanced US(CEUS)to a new qualitative level.展开更多
Objeelive To prepare and characterize polyelectrolyte multilayer film coated microbubbles for use as ultrasound contrast agent （UCA） and evaluate its effects in ultrasonic imaging on normal rabbit＇s fiver parenchym...Objeelive To prepare and characterize polyelectrolyte multilayer film coated microbubbles for use as ultrasound contrast agent （UCA） and evaluate its effects in ultrasonic imaging on normal rabbit＇s fiver parenchyma. Methods Perfluorocarbon （PFC）-containing microbubbles （ST68-PFC） were prepared by sonication based on suffactant （ Span 60 and Tween 80）. Subsequently, the resulting ST68-PFC microbubbles were coated using oppositely charged polyelectrolytes by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction. The enhancement effects in ultrasonic imaging on normal rabbit＇s liver parenchyma were assessed. Results The obtained microbubbles exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film coated UCA effectively enhanced the imaging of rabbit＇s liver parenchyma. Conclusions The novel microbubbles UCA coated with polyelectrolyte multilayer, when enabled more function, has no obvious difference in enhancement effects compared with the pre-modified microbubbles. The polymers with chemically active groups （ such as amino group and carboxyl group） can be used as the outermost layer for attachment of targeting ligands onto microbubbles, allowing selective targeting of the microbubbles to combine with desired sites.展开更多
A kind of thrombus-targeted lipid-coated microbubbles were prepared, and the target prop- erty of the microbubbles and the effects of different methods detecting thrombosis in vessels were ob- served. Phospholipid-coa...A kind of thrombus-targeted lipid-coated microbubbles were prepared, and the target prop- erty of the microbubbles and the effects of different methods detecting thrombosis in vessels were ob- served. Phospholipid-coated microbubbles were prepared by membrane-hydration method. Throm- bus-targeted lipid-coated fluorocarbon microbubbles were labeled with specific fluorescence and then integrated to the thrombus in vivo and ex vivo through an avidin biotin system. The thrombus was im- mediately observed for the distribution and property of the thrombus-targeted microbubbles under the optical microscope, fluorescence microscope and transmission electron microscope. The carotid throm- bosis models were set up in rabbits, and the effects of different methods detecting thrombosis in vessels were observed. The diameter of the phospholipid-coated microbubbles was 0.8-2.5μm, and even reached nanoscale in some of them. The zeta electric potential was about -11 mV and the concentration was about 1.08×10μmL. Immunofluorescence of rapid frozen sections in vivo and ex vivo showed that massive targeted lipid-coated microbubbles flocked around fresh blood clots and some aggregated within them under the light and fluorescence microscope. The number of aggregated microbubbles ex vivo was greater than that observed in the experiment in vivo, and the fluorescence observed in the ex- periment ex vivo was stronger than that in the experiment in vivo. The same imaging was observed un- der the electron microscope. Models of carotid thrombosis in rabbits were established successfully. Ef- fects of detecting thrombosis by means of thrombosis-targeted microbubble ultrasonoraphy and Sono Vue ultrasonography in vessels were more satisfactory than those by Color Doplor Flow Imaging （CDFI）, ordinary microbubbles and Three Dimensions-time of flight MR angiography （3D-TOF-MRA） （P〈0.01）. Compared to ordinary microbubbles ultrasonography, thrombosis-targeted microbubbles ultrasonography had the advantages whenever in imaging quality or in imaging time. Thrombus-targeted phospholipid-coated microbubbles were prepared successfully by membrane-hydration method. They could aggregate rapidly in fresh blood clots and enter deep into the internal part of the thrombus both in vivo and ex vivo, and had the targeted property of strongly conjugating with the thrombus. Compared to other thrombosis detection methods, ultrasonography with thrombosis-targeted microbubbles has obvious advantages in detecting thrombosis in vessels, mainly in： non-invasiveness, safety, good image quality, accuracy, and longer imaging time.展开更多
The most effective sequence of small interfering RNA（si RNA） silencing STAT3 of psoriatic keratinocytes（KCs） was screened out,and the effects of the most effective si RNA combined with ultrasonic irradiation and S...The most effective sequence of small interfering RNA（si RNA） silencing STAT3 of psoriatic keratinocytes（KCs） was screened out,and the effects of the most effective si RNA combined with ultrasonic irradiation and Sono Vue microbubbles on the expression of STAT3 of KCs and the dose-and time-response were investigated.Three chemically-synthetic si RNAs targeting STAT3 carried by Lipofectamine 3000 were transfected into KCs,and the effects on STAT3 expression were detected,then the most effective si RNA was selected for the subsequent experiments.The negative controls of siR NA（si RNA-NC） labeled with Cy3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and Sono Vue microbubbles were transfected into KCs,then the optimal parameters of ultrasonic irradiation were determined.The most effective si RNA carried by Lipofectamine 3000 combined with ultrasonic irradiation at the optimal parameters and Sono Vue microbubbles was transfected into KCs,and the dose-and time-response of RNA interference was determined.The effect of RNA interference by the most effective si RNA at the optimal time and dose carried by Lipofectamine 3000 combined with ultrasonic irradiation and Sono Vue microbubbles（LUS group） was compared with that only carried by Lipofectamine 3000（L group）.The results showed that si RNA-3 achieved the highest silencing efficacy.0.5 W/cm2 and 30 s were selected as the parameters of ultrasonic irradiation.The si RNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and Sono Vue microbubbles could effectively knock down the STAT3 expression at m RNA and protein levels in dose-and time-dependent manners determined at 100 nmol/L with maximum downregulation on m RNA at 48 h,and on protein at 72 h after transfection.The LUS group achieved the highest silencing efficacy.It was concluded that si RNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoV ue microbubbles could effectively knock down the STAT3 expression in psoriatic KCs,and the optimized transfection condition and the sequence of si RNA-3 could serve for further research on gene therapy of psoriasis.展开更多
Multi-layer microbubble has great potential in enabling the corporation of medical imaging with tumor therapy such as drug and gene delivery of therapeutics or other functional materials in medical applications. Micro...Multi-layer microbubble has great potential in enabling the corporation of medical imaging with tumor therapy such as drug and gene delivery of therapeutics or other functional materials in medical applications. Microfluidic technique has advanced over the last decade and showed great promise in replacing traditional microbubble generating method. In this paper, a multi-layer microbubble structure was produced with the aspect as potentially used for drug loaded microbubble contrast agents.展开更多
Theoretical studies on the multi-bubble interaction are crucial for the in-depth understanding of the mechanism behind the applications of ultrasound contrast agents （UCAs） in clinics. A two-dimensional （2D） axisy...Theoretical studies on the multi-bubble interaction are crucial for the in-depth understanding of the mechanism behind the applications of ultrasound contrast agents （UCAs） in clinics. A two-dimensional （2D） axisymmetric finite element model （FEM） is developed here to investigate the bubble-bubble interactions for UCAs in a fluidic environment. The effect of the driving frequency and the bubble size on the bubble interaction tendency （viz., bubbles＇ attraction and repulsion）, as well as the influences of bubble shell mechanical parameters （viz., surface tension coefficient and viscosity coefficient） are discussed. Based on FEM simulations, the temporal evolution of the bubbles＇ radii, the bubble-bubble distance, and the distribution of the velocity field in the surrounding fluid are investigated in detail. The results suggest that for the interacting bubble-bubble couple, the overall translational tendency should be determined by the relationship between the driving frequency and their resonance frequencies. When the driving frequency falls between the resonance frequencies of two bubbles with different sizes, they will repel each other, otherwise they will attract each other. For constant acoustic driving parameters used in this paper, the changing rate of the bubble radius decreases as the viscosity coefficient increases, and increases first then decreases as the bubble shell surface tension coefficient increases, which means that the strength of bubble-bubble interaction could be adjusted by changing the bubble shell visco-elasticity coefficients. The current work should provide a powerful explanation for the accumulation observations in an experiment, and provide a fundamental theoretical support for the applications of UCAs in clinics.展开更多
Microbubbles loaded with magnetic nanoparticles(MMBs) have attracted increasing interests in multimode imaging and drug/gene delivery and targeted therapy. However, the dynamic behaviors generated in diagnostic and th...Microbubbles loaded with magnetic nanoparticles(MMBs) have attracted increasing interests in multimode imaging and drug/gene delivery and targeted therapy. However, the dynamic behaviors generated in diagnostic and therapeutic applications are not clear. In the present work, a novel theoretical model of a single MMB was developed, and the dynamic responses in an infinite viscous fluid were investigated under simultaneous exposure to magnetic and acoustic fields. The results showed that the amplitude reduces and the resonant frequency increases with the strength of the applied steady magnetic field and the susceptibility of the magnetic shell. However, the magnetic field has a limited influence on the oscillating. It is also noticed that the responses of MMB to a time-varying magnetic field is different from a steady magnetic field. The subharmonic components increase firstly and then decrease with the frequency of the magnetic field and the enhanced effect is related to the acoustic driving frequency. It is indicated that there may be a coupling interaction effect between the acoustic and magnetic fields.展开更多
Background:We aimed to prepare a non-invasive,reproducible,and controllable rat model of intracerebral hemorrhage with focused ultrasound(FUS).Methods:A rat intracerebral hemorrhage(ICH)model was established by combin...Background:We aimed to prepare a non-invasive,reproducible,and controllable rat model of intracerebral hemorrhage with focused ultrasound(FUS).Methods:A rat intracerebral hemorrhage(ICH)model was established by combining FUS and microbubbles(μBs),and edaravone was used to verify whether the free radical scavenger had a protective effect on the model.The brain tissue of each group was sectioned to observe the gross histology,blood-brain barrier(BBB)permeability,cerebral infarction volume,and histopathological changes.Results:Compared with the FUS group,the BBB permeability was significantly increased in the FUS+μBs(F&B)group(p=0.0021).The second coronal slice in the F&B group had an obvious hemorrhage lesion,and the FUS+μBs+edaravone(F&B&E)group had smaller hemorrhage areas;however,ICH did not occur in the FUS group.The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group(p=0.0030)and F&B&E group(p=0.0208).HE staining results showed that nerve fibrinolysis,neuronal necrosis,microglia production,and erythrocytes were found in both the F&B group and the F&B&E group,but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group.Conclusions:A rat ICH model was successfully prepared using theμBs assisted FUS treatment,and edaravone had a therapeutic effect on this model.This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.展开更多
Objectives and Methods: Both the concentration and the size of contrast microbubbles are the important factors that affect the quality of intravenous myocardial contrast echocardiography (IVMCE) image, but the interac...Objectives and Methods: Both the concentration and the size of contrast microbubbles are the important factors that affect the quality of intravenous myocardial contrast echocardiography (IVMCE) image, but the interactions between microbubbles and ultrasound are poorly understood. In order to select optimal ultrasound exposure condition for IVMCE, the influences of ultrasound power, frequency and exposure time on sonicated microbubbles stability were evaluated by a 2 x 2 x 4 factorial analysis in the study. Results: It was found that the concentration of microbubbles was decreased when the ultrasound power increased or the exposure time of ultrasound prolonged (P < 0. 001). The frequency of ultrasound did not influence the concentration of the bubbles (P = 0. 061 ). The higher the power or the frequency and the longer the exposuretime, the smaller the mean size of the contrast bubbles (power, P = 0.004; frequency, P < 0.001); exposure time, P < 0. 00l ). The controlling factors of the condition did not interactively affect the concentration or the mean size of contrast mi- crobubbles. Conclusion: These findings could allow us to select ultrasound at lower frequency, lower ultrasound power and to reduce the exposure time bine of microbubbles to ultrasound for the improvement in the contrast effect in IVMCE.展开更多
Microbubbles can enhance the detection in noninvasive ultrasound imaging.Recently,targeted microbubbles have been developed to selectively adhere to specific and overexpressed p molecules in endothelial cells in some ...Microbubbles can enhance the detection in noninvasive ultrasound imaging.Recently,targeted microbubbles have been developed to selectively adhere to specific and overexpressed p molecules in endothelial cells in some pathologic conditions.However,the law of展开更多
Aim To research on a stable microbubble with good acoustic properties and excellent imaging enhancing effect, and to make it to be a promising agent for the enhancement of ultrasound imaging in the ultrasound diagnosi...Aim To research on a stable microbubble with good acoustic properties and excellent imaging enhancing effect, and to make it to be a promising agent for the enhancement of ultrasound imaging in the ultrasound diagnosis of cardiovascular system diseases. Methods The morphology, size and zeta potential of lipid-coated microbubbles （LCM）, the acoustic properties of backscatter, and the second harmonic scatter of LCM were determined. Furthermore, the relationship between the concentrations and the amplitude values of the second harmonic was investigated by testing the intensities of the second harmonic at different concentrations. The imaging effect of LCM was also studied in vitro. Results The mean diameter of LCM was 3.38 μm with 95% of the bubbles under 5 μm. The scatter signal generated by microbubbles was observed under different concentrations in the bistatic modes while the position of transmitting transducer and receiving transducer was orthogonal. The intensity of the second harmonic scatter fell with the decrease of microbubble concentration. The increase rate of the second harmonic amplitude values generated by the microbubbles versus that by physiological saline was linear with the natural logarithm of bubble concentrations. The LCM could enhance the ultrasound image of thrombus. Conclusion The LCM exhibited good physical state and acoustic properties, which could increase the imaging quality.展开更多
The development of low-frequency ultrasound imaging technology and the improvement of ultrasound contrast agent production technology mean that they play an increasingly important role in tumor therapy. The interactio...The development of low-frequency ultrasound imaging technology and the improvement of ultrasound contrast agent production technology mean that they play an increasingly important role in tumor therapy. The interaction between ultrasound and microbubbles and their biological effects can transfer and release microbubbles carrying genes and drugs to target tissues, mediate the apoptosis of tumor cells, and block the embolization of tumor microvasculature. With the optimization of ultrasound parameters, the development of targeted microbubbles, and the emergence of various composite probes with both diagnostic and therapeutic functions, low-frequency ultrasound combined with microbubble contrast agents will bring new hope for clinical tumor treatment.展开更多
基金supported by the National Natural Science Foundation of China(52074317)the PetroChina Group Major Special Project(2021ZZ01-03)the National Key Research and Development Program(2023YFF0614100).
文摘Non-chemical CO_(2) microbubbles as a mobility control technology in enhanced oil recovery(EOR)and carbon sequestration are becoming attractive.In this study,the EOR mechanisms of non-chemical CO_(2) microbubble(MB)in low permeability reservoirs are experimentally investigated by the nuclear magnetic resonance(NMR)technology.This study reveals,for the first time,the EOR mechanisms of MB in a heterogeneous reservoir and its effect on pore structure.First,mobility reduction factors of MB with various gas–liquid ratios were determined,with MB at a gas–liquid ratio of 1 exhibiting the best performance under experimental conditions.Second,the coreflood experiments with NMR scanning were performed to reveal the EOR mechanisms of MB.It was observed that MB achieved an incremental oil recovery of 13.49% and 22.80%in the core sample with a permeability of 9.51×10^(−3) and 2.23×10^(−3)μm^(2),respectively.Benefiting from MB's conformance control,the total oil recovery was increased from 38.34%to 54.57% of original oil in place by MB in parallel core flood experiments.Third,the NMR tests demonstrated that MB significantly reduced residual oil in core samples,especially in small pore areas,which highlights the improvement of sweep efficiency by MB.Lastly,the effect of MB on pore structure was studied.The NMR tests indicated a significant increase in pore space after 1 pore volume of MB flooding.Minerals in the core sample were dissolved,leading to an increase in permeability and porosity of the core sample by 17.01%and 0.31%,respectively.Overall,the results of this study provide valuable insights into the EOR mechanisms of MB at the pore scale and offer implications for EOR and carbon sequestration in low-permeability reservoirs.
文摘BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.
基金Supported by a grant from Sci-Tech Program Foundation of GuangdongProvince (No. 2006B35901009).
文摘Objective:To evaluate the impact of the diameter of SonoVue microbubbles on binding characteristics, including the adhesion rate and stability, of a new contrast agent targeted to choriocarcinoma cells(JARs) in vitro, in order to establish a foundation to explore targeted ultrasound imaging for localization of tumor cell antigens and increase the early diagnostic rate for tumors.Methods:The objects were divided into three groups:the large microbubble group(n = 15), the middling microbubble group(n = 15) and the tiny microbubble group(n = 15).The rosette formation rate was counted.JARs were calculated by flow cytometry(FCM).The targeted contrast agent was prepared by mixing SonoVue microbubbles of different diam-eter with rabbit anti-human chorionic gonadotrophin(HCG) antibody.The binding rates of the targeted contrast agent to JARs before and after PBS rinse were analyzed.Results:The binding rate was significantly lower in the large microbubble group(61.7 ± 1.8)% than in the middling microbubble group(82.6 ± 4.5)% and the tiny microbubble group(91.3 ± 5.8)%(P < 0.05).The binding rates of different diameter microbubbles to JARs before and after PBS rinse were different.The middling microbubbles were the most stable ones, with the binding rate of(82.3 ± 4.5)% and(80.4 ± 3.9)% before and after PBS rinse(P > 0.05).The binding rates of the targeted microbubbles labeled with fluorescence to JARs were 68.6%, 81.3% and 89.3% in the large microbubble group, the middling microbubble group and the tiny microbubble group, respectively(P < 0.05).Conclu-sion:The binding capacity of the targeted SonoVue microbubbles to JARs is related to the diameter of the microbubble, which is determined by the shaking method before preparation.Modulating the diameter of SonoVue microbubbles may increase the binding rate and stability of targeted microbubbles to JARs, thus to improve the image of JARs.
基金sponsored by National Key Research and Development Plan(No.2017YFC0107300 and No.2017YFC0107303)
文摘Objective： To explore the safety of ultrasound and microbubbles for enhancing the chemotherapeutic sensitivity of malignant tumors in the digestive system in a clinical trial, as well as its efficacy.Methods： From October 2014 to June 2016, twelve patients volunteered to participate in this study. Eleven patients had hepatic metastases from tumors of the digestive system, and one patient had pancreatic carcinoma. According to the mechanical index （MI） in the ultrasound field, patients were classified into four groups with MIs of 0.4, 0.6, 0.8 and 1.0. Within half an hour after chemotherapy, patients underwent ultrasound scanning with ultrasound microbubbles （SonoVue） to enhance the efficacy of chemotherapy. All adverse reactions were recorded and were classified in 4 grades according to the Common Terminology Criteria for Adverse Events version 4.03 （CTCAE V4.03）. Tumor responses were evaluated by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria. All the patients were followed up until progression.Results： All the adverse reactions recorded were level 1 or level 2. No local pain occurred in any of the patients. Among all the adverse reactions, fever might be related to the treatment with ultrasound combined with microbubbles. Six patients had stable disease （SD）, and one patient had a partial response （PR） after the first cycle of treatment. At the end of follow-up, tumor progression was restricted to the original sites, and no new lesions had appeared.Conclusions： Our preliminary data showed the potential role of a combined treatment with ultrasound and microbubbles in enhancing the chemotherapeutic sensitivity of malignant tumors of the digestive system. This technique is safe when the MI is no greater than 1.0.
基金supported by the National Basic Research Program of China(Grant No.2011CB707900)the National Natural Science Foundation of China(Grant Nos.10974093,11011130201,and 10904094)+2 种基金the Fundamental Research Funds for the Central Universities of China(Grant Nos.1103020402,1116020410,and 1112020401)the Prior Academic Program Development of Jiangsu Higher Education Institutions,Chinathe State key Laboratory of Acoustics of Ministry of Education,China
文摘Secondary radiation force can be an attractive force causing aggregates of encapsulated microbubbles in ultrasonic molecular imaging. The influence of the secondary radiation force on aggregation between two coated bubbles is investigated in this study. Numerical calculations are performed based on four simultaneous differential equations of radial and translational motions. Results show that the secondary force can change from attraction to repulsion during approach, and stable microbubble pairs can be formed in the vicinity of resonant regions; the possibility of microbubble aggregations can be reduced by using low exciting amplitude, ultrasonic frequencies deviating from the resonant frequencies or microbubbles with small compressibility.
基金This Project was supported by a grant from the NationalSciences Foundtion of China (No. 39970 30 8)
文摘The backscatter from sonicated albumin microbubbles (Albunex) was analyzed using acoustic densitometry in an in vitro pulsatile heart model to evaluate the effects of pressure on the backscatter from Albunex, and the cardiac cyclic changes of intracardiac backscatter from sonicated albumin microbubbles in 16 healthy persons were analyzed. It was found that the Albunex microbubbles were compressed in systole and decompressed in diastole, causing corresponding changes of backscatter in cardiac cycle. Although the intensities of backscatter in diastole and systole were related to the concentration of microbubbles, the concentration of microbubbles had no effect on the difference of end-diastolic and end-systolic backscatter. The difference of the backscatter was highly correlated with end-systolic pressure (r=0.96, P=0.001). In human studies, we also observed same intracardiac cyclic changes of backscatter from sonicated albumin microbubbles. Our study indicates that it is possible to evaluate the intracardiac pressure non-invasively by analyzing the intracardiac backscatter from the microbubbles with acoustic densitometry.
文摘Objective: To investigate the role and potential mechanism of CXCR4 in promoting targeted homing of bone marrow mesenchymal stem cells(BMSCs) with ultrasound-exposed microbubbles(UM) pretreatment. Methods: Third generation BMSCs were divided into four groups control group, ultrasound(US) group, UM group and ultrasound-exposed microbubbles plus catalase group. RT-PCR and western blot were performed to determine the levels of CXCR4 m RNA transcription and protein expression, respectively. Third generation BMSCs were labeled with Fluo-α/AM and divided into three groups: control group, US group and UM group, and flurorescence intensities in the cells were observed immediately, 5 min and 15 min after intervention underflurorescence microscope. The calcium iron levels in the cells were analyzed. BMSCs were divided into i ve group: group A without calcium in the medium, group B, group C, group D and group E containing calcium chloride with concentration of l mol, 2 mol, 4mol, anti-calciurn-sensing receptor antibody, respectively. RT-PCR and western blot were performed to determine the levels of CXCR4 m RNA transcription and proteins expression of the third generation BMSCs of each group, respectively. Results: The levels of CXCR4 m RNA transcription and protein expression between US group and control group had no statistically signii cant dif erence(P>0.05) shown by RT-PCR and western blot; the transcription level in the UM group was signii cantly higher than that in US group and control group(P<0.05); and in the ultrasound-exposed microbubbles plus catalase group, the transcription level was much lower than that in UM group. Fluorescence intensify in the cells of US group had no signii cant dif erence compared with that in the cells of the control group(P>0.05), which in the cells of UM group was signii cantly higher than that in the cells of both US group and control group(P<0.05). Compared to group A, expressions of CXCR4 of group B to D were signii cantly increased in concentration-dependent manner showed by RT-PCR and western blot(P< 0.05). Compared to group C, expressions of CXCR4 of group E were signii cantly decreased(P< 0.05). Conclusions: UM can promote the inl ux of calcium in BMSCs and increase m RNA transcription and protein expression of CXCR4. The latter may partly be caused by influx of calcium.
基金supported by the National Natural Science Foundation of China-Sichuan Joint Fund Key Program(No.NSFCU21A20417)the National Natural Science Foundation of China(Nos.NSFC31930067,81971622,82272003)the 135 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYGD18002,China)。
文摘Ultrasonography is an important complement to clinical diagnosis,and the application of microbubbles effectively improved diagnostic accuracy in echography.In scientific research,the sizes of microbubbles range from nanometers to microns.By optimizing the fabrication process,bubble sizes and ultrasound parameters,microbubbles can also be used for drug delivery and therapeutic monitoring.In this review,we summarize the recent advances in the diagnosis and treatment of microbubbles according to their different components.Modification of microbubble shells allows for more accurate imaging and detection and the combined utilization of US-targeted MB destruction(UTMD)allows for non-invasive,precise and targeted delivery of drug molecules to pathological tissues.These features pave the way for the emerge of theranostic microbubbles by combination of functional compositions and the application of multifunctional materials.Theranostic microbubbles allow for the simultaneous process of diagnosis,visualization of drug delivery and therapeutic monitoring.Ultimately,theranostic microbubbles are promising in clinical practice and would enhance contrast-enhanced US(CEUS)to a new qualitative level.
基金Supported by the Program for New Century Excellent in University of China(30740061)the National Natural Science Foundation of China(30672001)
文摘Objeelive To prepare and characterize polyelectrolyte multilayer film coated microbubbles for use as ultrasound contrast agent （UCA） and evaluate its effects in ultrasonic imaging on normal rabbit＇s fiver parenchyma. Methods Perfluorocarbon （PFC）-containing microbubbles （ST68-PFC） were prepared by sonication based on suffactant （ Span 60 and Tween 80）. Subsequently, the resulting ST68-PFC microbubbles were coated using oppositely charged polyelectrolytes by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction. The enhancement effects in ultrasonic imaging on normal rabbit＇s liver parenchyma were assessed. Results The obtained microbubbles exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film coated UCA effectively enhanced the imaging of rabbit＇s liver parenchyma. Conclusions The novel microbubbles UCA coated with polyelectrolyte multilayer, when enabled more function, has no obvious difference in enhancement effects compared with the pre-modified microbubbles. The polymers with chemically active groups （ such as amino group and carboxyl group） can be used as the outermost layer for attachment of targeting ligands onto microbubbles, allowing selective targeting of the microbubbles to combine with desired sites.
基金supported by National Natural Science Foundation of China (No. 30672207)
文摘A kind of thrombus-targeted lipid-coated microbubbles were prepared, and the target prop- erty of the microbubbles and the effects of different methods detecting thrombosis in vessels were ob- served. Phospholipid-coated microbubbles were prepared by membrane-hydration method. Throm- bus-targeted lipid-coated fluorocarbon microbubbles were labeled with specific fluorescence and then integrated to the thrombus in vivo and ex vivo through an avidin biotin system. The thrombus was im- mediately observed for the distribution and property of the thrombus-targeted microbubbles under the optical microscope, fluorescence microscope and transmission electron microscope. The carotid throm- bosis models were set up in rabbits, and the effects of different methods detecting thrombosis in vessels were observed. The diameter of the phospholipid-coated microbubbles was 0.8-2.5μm, and even reached nanoscale in some of them. The zeta electric potential was about -11 mV and the concentration was about 1.08×10μmL. Immunofluorescence of rapid frozen sections in vivo and ex vivo showed that massive targeted lipid-coated microbubbles flocked around fresh blood clots and some aggregated within them under the light and fluorescence microscope. The number of aggregated microbubbles ex vivo was greater than that observed in the experiment in vivo, and the fluorescence observed in the ex- periment ex vivo was stronger than that in the experiment in vivo. The same imaging was observed un- der the electron microscope. Models of carotid thrombosis in rabbits were established successfully. Ef- fects of detecting thrombosis by means of thrombosis-targeted microbubble ultrasonoraphy and Sono Vue ultrasonography in vessels were more satisfactory than those by Color Doplor Flow Imaging （CDFI）, ordinary microbubbles and Three Dimensions-time of flight MR angiography （3D-TOF-MRA） （P〈0.01）. Compared to ordinary microbubbles ultrasonography, thrombosis-targeted microbubbles ultrasonography had the advantages whenever in imaging quality or in imaging time. Thrombus-targeted phospholipid-coated microbubbles were prepared successfully by membrane-hydration method. They could aggregate rapidly in fresh blood clots and enter deep into the internal part of the thrombus both in vivo and ex vivo, and had the targeted property of strongly conjugating with the thrombus. Compared to other thrombosis detection methods, ultrasonography with thrombosis-targeted microbubbles has obvious advantages in detecting thrombosis in vessels, mainly in： non-invasiveness, safety, good image quality, accuracy, and longer imaging time.
基金supported by National Natural Science Foundation of China(No.81441126)
文摘The most effective sequence of small interfering RNA（si RNA） silencing STAT3 of psoriatic keratinocytes（KCs） was screened out,and the effects of the most effective si RNA combined with ultrasonic irradiation and Sono Vue microbubbles on the expression of STAT3 of KCs and the dose-and time-response were investigated.Three chemically-synthetic si RNAs targeting STAT3 carried by Lipofectamine 3000 were transfected into KCs,and the effects on STAT3 expression were detected,then the most effective si RNA was selected for the subsequent experiments.The negative controls of siR NA（si RNA-NC） labeled with Cy3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and Sono Vue microbubbles were transfected into KCs,then the optimal parameters of ultrasonic irradiation were determined.The most effective si RNA carried by Lipofectamine 3000 combined with ultrasonic irradiation at the optimal parameters and Sono Vue microbubbles was transfected into KCs,and the dose-and time-response of RNA interference was determined.The effect of RNA interference by the most effective si RNA at the optimal time and dose carried by Lipofectamine 3000 combined with ultrasonic irradiation and Sono Vue microbubbles（LUS group） was compared with that only carried by Lipofectamine 3000（L group）.The results showed that si RNA-3 achieved the highest silencing efficacy.0.5 W/cm2 and 30 s were selected as the parameters of ultrasonic irradiation.The si RNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and Sono Vue microbubbles could effectively knock down the STAT3 expression at m RNA and protein levels in dose-and time-dependent manners determined at 100 nmol/L with maximum downregulation on m RNA at 48 h,and on protein at 72 h after transfection.The LUS group achieved the highest silencing efficacy.It was concluded that si RNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoV ue microbubbles could effectively knock down the STAT3 expression in psoriatic KCs,and the optimized transfection condition and the sequence of si RNA-3 could serve for further research on gene therapy of psoriasis.
文摘Multi-layer microbubble has great potential in enabling the corporation of medical imaging with tumor therapy such as drug and gene delivery of therapeutics or other functional materials in medical applications. Microfluidic technique has advanced over the last decade and showed great promise in replacing traditional microbubble generating method. In this paper, a multi-layer microbubble structure was produced with the aspect as potentially used for drug loaded microbubble contrast agents.
基金Projects supported by the National Natural Science Foundation of China(Grant Nos.11474161,11474001,116741731,1774166,11774168,81527803,81627802,and 81420108018)the Fundamental Research Funds for the Central Universities,China(Grant No.020414380109)the Qing Lan Project,China
文摘Theoretical studies on the multi-bubble interaction are crucial for the in-depth understanding of the mechanism behind the applications of ultrasound contrast agents （UCAs） in clinics. A two-dimensional （2D） axisymmetric finite element model （FEM） is developed here to investigate the bubble-bubble interactions for UCAs in a fluidic environment. The effect of the driving frequency and the bubble size on the bubble interaction tendency （viz., bubbles＇ attraction and repulsion）, as well as the influences of bubble shell mechanical parameters （viz., surface tension coefficient and viscosity coefficient） are discussed. Based on FEM simulations, the temporal evolution of the bubbles＇ radii, the bubble-bubble distance, and the distribution of the velocity field in the surrounding fluid are investigated in detail. The results suggest that for the interacting bubble-bubble couple, the overall translational tendency should be determined by the relationship between the driving frequency and their resonance frequencies. When the driving frequency falls between the resonance frequencies of two bubbles with different sizes, they will repel each other, otherwise they will attract each other. For constant acoustic driving parameters used in this paper, the changing rate of the bubble radius decreases as the viscosity coefficient increases, and increases first then decreases as the bubble shell surface tension coefficient increases, which means that the strength of bubble-bubble interaction could be adjusted by changing the bubble shell visco-elasticity coefficients. The current work should provide a powerful explanation for the accumulation observations in an experiment, and provide a fundamental theoretical support for the applications of UCAs in clinics.
基金the support of the National Natural Science Foundation of China (Grant Nos. 12074238 and 11974232)。
文摘Microbubbles loaded with magnetic nanoparticles(MMBs) have attracted increasing interests in multimode imaging and drug/gene delivery and targeted therapy. However, the dynamic behaviors generated in diagnostic and therapeutic applications are not clear. In the present work, a novel theoretical model of a single MMB was developed, and the dynamic responses in an infinite viscous fluid were investigated under simultaneous exposure to magnetic and acoustic fields. The results showed that the amplitude reduces and the resonant frequency increases with the strength of the applied steady magnetic field and the susceptibility of the magnetic shell. However, the magnetic field has a limited influence on the oscillating. It is also noticed that the responses of MMB to a time-varying magnetic field is different from a steady magnetic field. The subharmonic components increase firstly and then decrease with the frequency of the magnetic field and the enhanced effect is related to the acoustic driving frequency. It is indicated that there may be a coupling interaction effect between the acoustic and magnetic fields.
基金National Natural Scientific Foundation of China(82071349,82027808,82171952,81771310)West China Hospital of Sichuan University Discipline Excellence Development 1·3·5 Engineering Project(Interdisciplinary Innovation Project,ZYYC08005,ZYJC18041)。
文摘Background:We aimed to prepare a non-invasive,reproducible,and controllable rat model of intracerebral hemorrhage with focused ultrasound(FUS).Methods:A rat intracerebral hemorrhage(ICH)model was established by combining FUS and microbubbles(μBs),and edaravone was used to verify whether the free radical scavenger had a protective effect on the model.The brain tissue of each group was sectioned to observe the gross histology,blood-brain barrier(BBB)permeability,cerebral infarction volume,and histopathological changes.Results:Compared with the FUS group,the BBB permeability was significantly increased in the FUS+μBs(F&B)group(p=0.0021).The second coronal slice in the F&B group had an obvious hemorrhage lesion,and the FUS+μBs+edaravone(F&B&E)group had smaller hemorrhage areas;however,ICH did not occur in the FUS group.The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group(p=0.0030)and F&B&E group(p=0.0208).HE staining results showed that nerve fibrinolysis,neuronal necrosis,microglia production,and erythrocytes were found in both the F&B group and the F&B&E group,but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group.Conclusions:A rat ICH model was successfully prepared using theμBs assisted FUS treatment,and edaravone had a therapeutic effect on this model.This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.
文摘Objectives and Methods: Both the concentration and the size of contrast microbubbles are the important factors that affect the quality of intravenous myocardial contrast echocardiography (IVMCE) image, but the interactions between microbubbles and ultrasound are poorly understood. In order to select optimal ultrasound exposure condition for IVMCE, the influences of ultrasound power, frequency and exposure time on sonicated microbubbles stability were evaluated by a 2 x 2 x 4 factorial analysis in the study. Results: It was found that the concentration of microbubbles was decreased when the ultrasound power increased or the exposure time of ultrasound prolonged (P < 0. 001). The frequency of ultrasound did not influence the concentration of the bubbles (P = 0. 061 ). The higher the power or the frequency and the longer the exposuretime, the smaller the mean size of the contrast bubbles (power, P = 0.004; frequency, P < 0.001); exposure time, P < 0. 00l ). The controlling factors of the condition did not interactively affect the concentration or the mean size of contrast mi- crobubbles. Conclusion: These findings could allow us to select ultrasound at lower frequency, lower ultrasound power and to reduce the exposure time bine of microbubbles to ultrasound for the improvement in the contrast effect in IVMCE.
基金supported by National Natural Science Foundation of China,No.30700151
文摘Microbubbles can enhance the detection in noninvasive ultrasound imaging.Recently,targeted microbubbles have been developed to selectively adhere to specific and overexpressed p molecules in endothelial cells in some pathologic conditions.However,the law of
文摘Aim To research on a stable microbubble with good acoustic properties and excellent imaging enhancing effect, and to make it to be a promising agent for the enhancement of ultrasound imaging in the ultrasound diagnosis of cardiovascular system diseases. Methods The morphology, size and zeta potential of lipid-coated microbubbles （LCM）, the acoustic properties of backscatter, and the second harmonic scatter of LCM were determined. Furthermore, the relationship between the concentrations and the amplitude values of the second harmonic was investigated by testing the intensities of the second harmonic at different concentrations. The imaging effect of LCM was also studied in vitro. Results The mean diameter of LCM was 3.38 μm with 95% of the bubbles under 5 μm. The scatter signal generated by microbubbles was observed under different concentrations in the bistatic modes while the position of transmitting transducer and receiving transducer was orthogonal. The intensity of the second harmonic scatter fell with the decrease of microbubble concentration. The increase rate of the second harmonic amplitude values generated by the microbubbles versus that by physiological saline was linear with the natural logarithm of bubble concentrations. The LCM could enhance the ultrasound image of thrombus. Conclusion The LCM exhibited good physical state and acoustic properties, which could increase the imaging quality.
基金Project supported by the Health and Family Planning Commission of Zhejiang Province(No.2017KY676),China
文摘The development of low-frequency ultrasound imaging technology and the improvement of ultrasound contrast agent production technology mean that they play an increasingly important role in tumor therapy. The interaction between ultrasound and microbubbles and their biological effects can transfer and release microbubbles carrying genes and drugs to target tissues, mediate the apoptosis of tumor cells, and block the embolization of tumor microvasculature. With the optimization of ultrasound parameters, the development of targeted microbubbles, and the emergence of various composite probes with both diagnostic and therapeutic functions, low-frequency ultrasound combined with microbubble contrast agents will bring new hope for clinical tumor treatment.
