Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics.Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment...Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics.Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound(US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents(UCAs)an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles(SPIOs), Cu S nanoparticles, DNA, si RNA, gold nanoparticles(GNPs), gold nanorods(GNRs), gold nanoshell(GNS), graphene oxides(GOs), polypyrrole(PPy) nanocapsules, Prussian blue(PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics.展开更多
Microbubbles have been used for many years now in clinical practice as contrast agents in ultrasound imaging.Recently,their therapeutic applications have also attracted more attention.However,the short circulation tim...Microbubbles have been used for many years now in clinical practice as contrast agents in ultrasound imaging.Recently,their therapeutic applications have also attracted more attention.However,the short circulation time(minutes)and relatively large size(two to ten micrometers)of currently used commercial microbubbles do not allow effective extravasation into tumor tissue,preventing efficient tumor targeting.Fortunately,more multifunctional and theranostic nanoparticles with some special advantages over the traditional microbubbles have been widely investigated and explored for biomedical applications.The way to synthesize an ideal ultrasound contrast agent based on nanoparticles in order to achieve an expected effect on contrast imaging is a key technique.Currently a number of nanomaterials,including liposomes,polymers,micelles,dendrimers,emulsions,quantum dots,solid nanoparticles etc.,have already been applied to pre or clinical trials.Multifunctional and theranostic nanoparticles with some special advantages,such as the tumor-targeted(passive or active),multi-mode contrast agents(magnetic resonance imaging,ultrasonography or fluorescence),carrier or enhancer of drug delivery,and combined chemo or thermal therapy etc.,are rapidly gaining popularity and have shown a promising application in the field of cancer treatment.In this mini review,the trends and the advances of multifunctional and theranostic nanoparticles are briefly discussed.展开更多
AIM: To analyze the application significance of ultrasound contrast agent in identification and diagnosis of ocular spaceoccupying lesions, and mainly analyze its advantages and problems. METHODS: Thirty-two represent...AIM: To analyze the application significance of ultrasound contrast agent in identification and diagnosis of ocular spaceoccupying lesions, and mainly analyze its advantages and problems. METHODS: Thirty-two representative literatures about the application of ultrasound contrast agent in diagnosis of spaceoccupying lesions at home and abroad were collected after focused on sorting the literature reporting the application of ultrasound contrast diagnostic technology in the diagnosis and identification of ocular spaceoccupying lesions in recent years. Its advantages and problems were retrospectively analyzed, and reasonable assessment on existing problems was made and possible solutions to the problems were proposed. RESULTS: As a new imaging diagnostic technique, the contrast-enhanced ultrasound, which can enhance the display of tumor microcirculation vessels and improve the tumor's ultrasound diagnostic capability, was analyzed. Through sorting and comprehensively analyzing the collected literatures, the positive rate of ocular spaceoccupying lesion diagnosis could be significantly improved with ultrasound contrast technology. Thus, the vascular perfusion in normal tissues and lesions was reflected objectively. According to the lesion's perfusion characteristics of the contrast agent plus with the performance features of two-dimensional ultrasound, the ocular spaceoccupying lesions can be accurately diagnosed, and this could provide clinicians with reliable research basis in this field. CONCLUSION: Ultrasound contrast examination is a new testing method, and ultrasound contrast agent can significantly enhance the ultrasonic detection signal, clearly show the blood perfusion in vessels and tissues, increase the image contrast resolution, and improve the lesion's detection capability in the microcirculation perfusion level, especially its important value in the diagnosis of ocular tumor.展开更多
Objective: To explore the role of the abnormal expression of miRNAs in the development process of non-small cell lung cancer and the feasibility of ultrasound microbubble-mediated gene therapy after transfecting antis...Objective: To explore the role of the abnormal expression of miRNAs in the development process of non-small cell lung cancer and the feasibility of ultrasound microbubble-mediated gene therapy after transfecting antisense miRNA-224 and miRNA-122 a plasmids into nonsmall cell lung cancer A549 cells. Methods: Antisense miRNA-224 and miRNA-122 a plasmids were transfected into non-small cell lung cancer A549 cells on the optimal ultrasound microbubble mediated condition. We set up a control group. The cell proliferation activity, apoptosis, invasion ability were detected by MTT assay, Annexin V-PE, Transwell invasion experiment and colony formation assay, respectively. Results: The expression of mi RNA-224 decreased and the expression of miRNA-122 a rose after the plasmids of target genes were transfected into non-small cell lung cancer A549 cells, and there were significant differences when compared with those of the control group(P<0.05). After the plasmids of target genes were transfected into A549 cells, the growth of antisense miRNA-224 and miRNA-122 a were inhibited, and the differences were significant as compared with the control group(P < 0.05). Besides, the inhibition of miRNA-122 a group was the most significant and there was statistically significant difference as compared with miRNA-224 group(t =-4.694, P = 0.009). After the plasmids of target genes were transfected into A549 cells, the proportion of apoptotic cells increased, the invasive cells were decreased and the clone ability reduced, and also there was a significant difference as compared with those of the control group(P < 0.05). What's more, the apoptotic peak appeared in miRNA-122 a group. Its invasion ability decreased most obviously(40.25 ± 3.97/visual field), the number of clone ability was 104.93 ± 4.87 and the inhibitory effect was the most obviously. There was statistically significant difference as compared with other groups(P < 0.05). Conclusions: A549 cells transfected by ultrasound microbubble-mediated antisense miRNA-224 and mi RNA-122 a plasmids possessed good transfection efficiency. The cell growth, invasion and colony forming abilities of transfected A549 cells were suppressed, which laid a solid foundation for the gene therapy of non-small cell lung cancer.展开更多
Objective 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 liver parenchyma...Objective 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 liver parenchyma.Methods Perfluorocarbon(PFC)-containing microbubbles(ST68-PFC)were prepared by sonication based on surfactant(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
AIM:To investigate the diagnosis of nonalcoholic steatohepatitis(NASH) using contrast ultrasonography in the NASH rat model.METHODS:The liver in methionine choline-deficient diet(MCDD) rats,a NASH model constructed by...AIM:To investigate the diagnosis of nonalcoholic steatohepatitis(NASH) using contrast ultrasonography in the NASH rat model.METHODS:The liver in methionine choline-deficient diet(MCDD) rats,a NASH model constructed by feeding an MCDD,was examined by contrast ultrasonography at weeks 2,4,8,12 and 16,with late phase images of contrast ultrasonography(Kupffer imaging) in which contrast enhancement was achieved by incorporation of a contrast agent by Kupffer cells(KCs),and images were compared to those in rats taking a regular chow.RESULTS:Decrease in contrast enhancement was observed first in MCDD rats at week 2.KCs were counted based on immunohistochemistry,but their numbers were not reduced and it was assumed that attenuation of contrast enhancement was attributable to reduced phagocytic activity of the KCs.CONCLUSION:It is suggested that clinical application of contrast ultrasonography may be valuable for noninvasive diagnosis of NASH.展开更多
The goal of this article is to establish the conditions of excitation where one has to deal with ultrasound contrast agent(UCA) microbubbles pulsating near biological tissues with spherical boundary in ultrasound fiel...The goal of this article is to establish the conditions of excitation where one has to deal with ultrasound contrast agent(UCA) microbubbles pulsating near biological tissues with spherical boundary in ultrasound field for targeted drug delivery and cavitation-enhanced thrombolysis, etc., and contributes to understanding of mechanisms at play in such an interaction. A modified model is presented for describing microbubble dynamics near a spherical boundary(including convex boundary and concave boundary) with an arbitrary-sized aperture angle. The novelty of the model is such that an oscillating microbubble is influenced by an additional pressure produced by the sound reflection from the boundary wall. It is found that the amplitude of microbubble oscillation is positively correlated to the curve radius of the wall and negatively correlated to the aperture angle of the wall and the sound reflection coefficient. Moreover, the natural frequency of the microbubble oscillation for such a compliable wall increases with the wall compliance, but decreases with the reduction of the wall size, indicating distinct increase of the natural frequency compared to a common rigid wall. The proposed model may allow obtaining accurate information on the radiation force and signals that may be used to advantage in related as drug delivery and contrast agent imaging.展开更多
Objective: To study on the preparation process of a new surfactant-based microbubble ultrasound contrast agent and to evaluate its contrast effects in vivo. Methods: Microbubble ultrasound contrast agent with three es...Objective: To study on the preparation process of a new surfactant-based microbubble ultrasound contrast agent and to evaluate its contrast effects in vivo. Methods: Microbubble ultrasound contrast agent with three ester surfactants and other additives as its shell materials was prepared by sonication. Sulfur hexafluoride was adopted as the inner gas of the microbubbles. New methods through the combination of optical microscope and some softwares were used to measure the size distribution and the concentration of the microbubbles. Some parameters such as the pH value of the phosphate buffer, quantity of the carboxylic methyl cellulose in the shell materials, selection of the ultrasound power and process time, were studied. Six hybirded dogs were used to verify the in vivo contrast imaging of the contrast agent using second harmonic power Doppler modality. Safety and persistent time of the agent inner animal body were also investigated. Results: Ultrasound contrast agent prepared in the experiment had an average microbubble diameter of 3.95 microns with concentration of 3.6×109 microbubbles per millilitre. Carboxylic methyl cellulose was found as an important shell material which had obviously effect on the microbubble stability and production even with a little quantity. The buffer pH value also had a key role on the microbubble formation and the final production. When the buffer pH value reached 7.4, there was no microbubble produced. Under the approximate microbubble production, process time could be shorten with the increasing ultrasound power. The obvious ultrasound contrast imaging effects were detected in the dog's heart chamber and liver as well as kidney using only one millilitre agent when diluted. The agent was found safe to the dogs. At the same time, persistent time of the agent was found over 20 min in the dog's body. Conclusion: The new ultrasound contrast agent prepared in the experiment has high microbubble production and concentration, narrow microbubble size distribution ranging in several microns, well stability, little dosage needed in the contrast, well safety to the dogs and long persistent time, obvious contrast imaging effect in the dog's heart chamber, kidney and liver. These experiment data indicate that the new ultrasound contrast agent with three ester surfactants and carboxylic methyl cellulose as its main shell materials can be further developed for clinical purposes.展开更多
Objective: To present a self-developed experimental system for basic studies of blood perfusion imaging and time-intensity evaluating based on ultrasound contrast agent. Methods: The experimental system performed the ...Objective: To present a self-developed experimental system for basic studies of blood perfusion imaging and time-intensity evaluating based on ultrasound contrast agent. Methods: The experimental system performed the image reconstruction and time-intensity processing with radio frequency signals. The system was comprised of ultra-high speed hardware data acquisition interface and low computational cost algorithms. The self-made contrast agent,blood mimic phantom and capillary phantom model were used to validate the experimental system. Results: The images acquired in blood phantoms with linear-array and curve-array transducers were given. The time-intensity curves corresponding to selected region of interested from image sequence were demonstrated. It was also shown the time-intensity based decay curves and a comparison of decay of ultrasound contrast agent under different ultrasound powers. Conclusion: Several experiments resulted from two in vitro phantom models show that the experimental system can be used to basic studies of blood perfusion and further clinical studies of microvasculature perfusion.展开更多
Coded excitation is useful for ultrasound contrast imaging to increase penetration and SNR, and improve the contrast to tissue ratio (CTR). The waveform of bubble response depends greatly on bubble size, the frequency...Coded excitation is useful for ultrasound contrast imaging to increase penetration and SNR, and improve the contrast to tissue ratio (CTR). The waveform of bubble response depends greatly on bubble size, the frequency and bandwidth of the excitation chirp signal. This makes the pulse compression filter based on square-law be wrong for bubbles with changing sizes. In this paper, an adaptive pulse compression (APC) filter for the second harmonic of microbubble with varying size distribution is proposed. The APC filter is designed based on the estimated power spectrum of the received bubble harmonic echoes. Theoretical analysis and simulation studies are presented for evaluating performance of the APC filter. For monodisperse bubble, the power improvement factor of the APC filter can be more than 20 dB.展开更多
Modelling and biomedical applications of ultrasound contrast agent(UCA) microbubbles have attracted a great deal of attention. In this review, we summarize a series of researches done in our group, including(i) the de...Modelling and biomedical applications of ultrasound contrast agent(UCA) microbubbles have attracted a great deal of attention. In this review, we summarize a series of researches done in our group, including(i) the development of an all-in-one solution of characterizing coated bubble parameters based on the light scattering technique and flow cytometry;(ii) a novel bubble dynamic model that takes into consideration both nonlinear shell elasticity and viscosity to eliminate the dependences of bubble shell parameters on bubble size;(iii) the evaluation of UCA inertial cavitation threshold and its relationship with shell parameters; and(iv) the investigations of transfection efficiency and the reduction of cytotoxicity in gene delivery facilitated by UCAs excited by ultrasound exposures.展开更多
Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer.These sub-micron particles are approxima...Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer.These sub-micron particles are approximately 10x smaller than clinically available microbubbles.This allows them to effectively traverse compromised physiological barriers and circulate for extended periods of time.While various aspects of nanobubble behavior have been previously examined,their behavior in human whole blood has not yet been explored.Accordingly,herein we examined,for the first time,the short and long-term effects of blood components on nanobubble acoustic response.We observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline(PBS),plasma,or red blood cell solutions(RBCs).Specifically,after introducing nanobubbles to fresh human whole blood,signal enhancement,or the magnitude of nonlinear ultrasound signal,gradually increased by 22.8±13.1%throughout our experiment,with peak intensity reached within 145 s.In contrast,nanobubbles in PBS had a stable signal with negligible change in intensity(1.7±3.2%)over 8 min.Under the same conditions,microbubbles made with the same lipid formulation showed a56.8±6.1%decrease in enhancement in whole blood.Subsequent confocal,fluorescent,and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RBCs,suggesting that direct interactions,or hitchhiking,of nanobubbles on RBCs in the presence of plasma may be a possible mechanism for the observed effects.This phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery,where RBC interaction with nanoparticles could be exploited to improve delivery efficiency.展开更多
Portal hypertension(PH)is a commonly observed syndrome in patients with cirrhosis and other chronic liver diseases(1).It is closely associated with severe clinical complications,including upper gastrointestinal hemorr...Portal hypertension(PH)is a commonly observed syndrome in patients with cirrhosis and other chronic liver diseases(1).It is closely associated with severe clinical complications,including upper gastrointestinal hemorrhage,ascites,hepatic encephalopathy,and liver failure(2-6).Portal vein pressure(PVP)is a prognostic indicator for patients with cirrhosis,and PH is a contraindication for hepatectomy(7,8).Currently,the gold standard for assessing PVP is the measurement of PVP gradient[hepatic venous pressure gradient(HVPG)],which is indirectly determined by placing a catheter in the hepatic vein(3).展开更多
Microbubbles have been the earliest and most widely used ultrasound contrast agents by virtue of their unique features:such as non-toxicity,intravenous inject-ability,ability to cross the pulmonary capillary bed,and s...Microbubbles have been the earliest and most widely used ultrasound contrast agents by virtue of their unique features:such as non-toxicity,intravenous inject-ability,ability to cross the pulmonary capillary bed,and significant enhancement of echo signals for the duration of the examination,resulting in essential preclinical and clinical applications.The use of microbubbles functional-ized with targeting ligands to bind to specific targets in the bloodstream has further enabled ultrasound molecular imaging.Nevertheless,it is very challenging to utilize targeted microbubbles for molecular imaging of extra-vascular targets due to their size.A series of acoustic nanomaterials have been developed for breaking free from this constraint.Especially,biogenic gas vesicles,gas-filled protein nanostructures from microorganisms,were engineered as thefirst biomolecular ultrasound contrast agents,opening the door for more direct visual-ization of cellular and molecular function by ultrasound imaging.The ordered protein shell structure and unique gasfilling mechanism of biogenic gas vesicles endow them with excellent stability and attractive acoustic responses.What’s more,their genetic encodability enables them to act as acoustic reporter genes.This article reviews the upgrading progresses of ultrasound contrast agents from microbubbles to biogenic gas vesicles,and the opportu-nities and challenges for the commercial and clinical translation of the nascentfield of biomolecular ultrasound.展开更多
Objective: To evaluate the curative effect of the Traditional Chinese Medicine (TCM) external therapy on knee osteoarthritis patients with different TCM constitutions using musculoskeletal ultrasonography and contrast...Objective: To evaluate the curative effect of the Traditional Chinese Medicine (TCM) external therapy on knee osteoarthritis patients with different TCM constitutions using musculoskeletal ultrasonography and contrast-enhanced ultrasonography, and to explore the application value of contrast-enhanced ultrasonography in knee joint diseases. Methods: A total of 57 patients diagnosed with knee osteoarthritis in Shaanxi University of Traditional Chinese Medicine from December 2019 to May 2021 were collected, and they were divided into qi stagnation and blood stasis type group (23 cases) and cold-dampness obstruction type group (34 cases) according to the traditional Chinese medicine method. All patients were given acupuncture combined with TCM fumigation and washing. All patients underwent musculoskeletal ultrasonography and contrast-enhanced ultrasonography before and after treatment, observed and recorded relevant data, and compared the treatment effects between the two groups. Results: 85.96% (49/57) of knee osteoarthritis (KOA) patients had suprapatellar bursa effusion, 42.1% (24/57) had iliotibial band bursae effusion, some of which had poor sound transmission, and thickened synovium was seen in most effusions, 33.33% (19/57) had osteophyte formation. Compared with before treatment, the depth of suprapatellar sac effusion in the Qi stagnation and blood stasis type group decreased after treatment (P Conclusion: Musculoskeletal contrast-enhanced ultrasonography was used to quantitatively evaluate the efficacy of TCM external therapy on KOA for different TCM constitutions. Dynamic observation of synovial lesions of knee osteoarthritis provides a valuable imaging method for evaluating the efficacy of traditional Chinese medicine.展开更多
Kidney transplantation(KT)is an effective treatment for end-stage renal disease.Despite their rate has reduced over time,post-transplant complications still represent a major clinical problem because of the associated...Kidney transplantation(KT)is an effective treatment for end-stage renal disease.Despite their rate has reduced over time,post-transplant complications still represent a major clinical problem because of the associated risk of graft failure and loss.Thus,post-KT complications should be diagnosed and treated promptly.Imaging plays a pivotal role in this setting.Grayscale ultrasound(US)with color Doppler analysis is the first-line imaging modality for assessing complications,although many findings lack specificity.When performed by experienced operators,contrast-enhanced US(CEUS)has been advocated as a safe and fast tool to improve the accuracy of US.Also,when performing CEUS there is potentially no need for further imaging,such as contrast-enhanced computed tomography or magnetic resonance imaging,which are often contraindicated in recipients with impaired renal function.This technique is also portable to patients’bedside,thus having the potential of maximizing the cost-effectiveness of the whole diagnostic process.Finally,the use of blood-pool contrast agents allows translating information on graft microvasculature into time-intensity curves,and in turn quantitative perfusion indexes.Quantitative analysis is under evaluation as a tool to diagnose rejection or other causes of graft dysfunction.In this paper,we review and illustrate the indications to CEUS in the post-KT setting,as well as the main CEUS findings that can help establishing the diagnosis and planning the most adequate treatment.展开更多
基金financially supported by the National Natural Science Foundation of China(Grant No.81501585)the Natural Science Foundation of Jiangsu Province of China(Grant No.BK20150348)+1 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.15KJB310019)China Postdoctoral Science Foundation(Grant No.2015M570475 and 2016T90496)
文摘Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics.Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound(US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents(UCAs)an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles(SPIOs), Cu S nanoparticles, DNA, si RNA, gold nanoparticles(GNPs), gold nanorods(GNRs), gold nanoshell(GNS), graphene oxides(GOs), polypyrrole(PPy) nanocapsules, Prussian blue(PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics.
基金Supported by National Natural Science Foundation of ChinaNo.81371570+3 种基金Key Project from Shanghai Health BureauNo.20114003Shanghai Talent Development Project from Shanghai Human Resource and Social Security BureauNo.2012045
文摘Microbubbles have been used for many years now in clinical practice as contrast agents in ultrasound imaging.Recently,their therapeutic applications have also attracted more attention.However,the short circulation time(minutes)and relatively large size(two to ten micrometers)of currently used commercial microbubbles do not allow effective extravasation into tumor tissue,preventing efficient tumor targeting.Fortunately,more multifunctional and theranostic nanoparticles with some special advantages over the traditional microbubbles have been widely investigated and explored for biomedical applications.The way to synthesize an ideal ultrasound contrast agent based on nanoparticles in order to achieve an expected effect on contrast imaging is a key technique.Currently a number of nanomaterials,including liposomes,polymers,micelles,dendrimers,emulsions,quantum dots,solid nanoparticles etc.,have already been applied to pre or clinical trials.Multifunctional and theranostic nanoparticles with some special advantages,such as the tumor-targeted(passive or active),multi-mode contrast agents(magnetic resonance imaging,ultrasonography or fluorescence),carrier or enhancer of drug delivery,and combined chemo or thermal therapy etc.,are rapidly gaining popularity and have shown a promising application in the field of cancer treatment.In this mini review,the trends and the advances of multifunctional and theranostic nanoparticles are briefly discussed.
文摘AIM: To analyze the application significance of ultrasound contrast agent in identification and diagnosis of ocular spaceoccupying lesions, and mainly analyze its advantages and problems. METHODS: Thirty-two representative literatures about the application of ultrasound contrast agent in diagnosis of spaceoccupying lesions at home and abroad were collected after focused on sorting the literature reporting the application of ultrasound contrast diagnostic technology in the diagnosis and identification of ocular spaceoccupying lesions in recent years. Its advantages and problems were retrospectively analyzed, and reasonable assessment on existing problems was made and possible solutions to the problems were proposed. RESULTS: As a new imaging diagnostic technique, the contrast-enhanced ultrasound, which can enhance the display of tumor microcirculation vessels and improve the tumor's ultrasound diagnostic capability, was analyzed. Through sorting and comprehensively analyzing the collected literatures, the positive rate of ocular spaceoccupying lesion diagnosis could be significantly improved with ultrasound contrast technology. Thus, the vascular perfusion in normal tissues and lesions was reflected objectively. According to the lesion's perfusion characteristics of the contrast agent plus with the performance features of two-dimensional ultrasound, the ocular spaceoccupying lesions can be accurately diagnosed, and this could provide clinicians with reliable research basis in this field. CONCLUSION: Ultrasound contrast examination is a new testing method, and ultrasound contrast agent can significantly enhance the ultrasonic detection signal, clearly show the blood perfusion in vessels and tissues, increase the image contrast resolution, and improve the lesion's detection capability in the microcirculation perfusion level, especially its important value in the diagnosis of ocular tumor.
基金Supported by Key Project of National Natural Science Foundation of China,No.30830040Outstanding Youth Funding Project of China,No.30325027Key Project of Natural Science Foundation of CQ CSTS,No.CSTC2006BA5020
文摘瞄准：为了调查非热的损坏的病理学的特征，由搏动的高紧张导致了与超声对比代理人(UCA ) 相结合的集中的超声(PHIFU ) ， SonoVue (Bracco 矿泉，米兰，意大利) 在兔子肝 VX2 肿瘤。方法：肝 VX2 肿瘤模型在 20 只兔子被建立，它随机被划分成与超声对比代理人组(PHIFU + UCA 组) 和假冒的组相结合的 PHIFU。在 PHIFU + UCA 组， SonoVue 的 0.2 mL 静脉内地被注入肿瘤，由 ISP 5900 W/cm2 的超声暴露列在后面。兔子在超声暴露以后有天被牺牲。暴露的肿瘤纸巾的标本在轻显微镜和传播电子显微镜下面病理地被获得并且观察。留下的肿瘤纸巾被去请染色的 2,3,5-Triphenyltetrazolium 氯化物(TTC ) 。结果：在染色的 TTC 前，在两个的肿瘤纸巾假冒并且 PHIFU + UCA 组类似于灰色的鱼肉。在染色的 TTC 以后，肿瘤纸巾是一致地染色的红，与在肿瘤织物和正常织物之间的一条清楚的边界。组织学的检查在 PHIFU + UCA 组显示出肿瘤房间损害的符号，与各种各样的尺寸，染色质着边和核固缩的细胞质的液泡。电子显微镜检查揭示了肿瘤房间体积减小，核固缩，染色质着边，拓宽的细胞间隙，在细胞质的高电子密度 apoptotic 身体和液泡的存在。结论：与 UCA 相结合的 PHIFU 的非热的效果能被用来切除兔子肝 VX2 肿瘤。
基金supported by Science and technology plan projects of Sichuan Province(Grant No.2015SZ0074)
文摘Objective: To explore the role of the abnormal expression of miRNAs in the development process of non-small cell lung cancer and the feasibility of ultrasound microbubble-mediated gene therapy after transfecting antisense miRNA-224 and miRNA-122 a plasmids into nonsmall cell lung cancer A549 cells. Methods: Antisense miRNA-224 and miRNA-122 a plasmids were transfected into non-small cell lung cancer A549 cells on the optimal ultrasound microbubble mediated condition. We set up a control group. The cell proliferation activity, apoptosis, invasion ability were detected by MTT assay, Annexin V-PE, Transwell invasion experiment and colony formation assay, respectively. Results: The expression of mi RNA-224 decreased and the expression of miRNA-122 a rose after the plasmids of target genes were transfected into non-small cell lung cancer A549 cells, and there were significant differences when compared with those of the control group(P<0.05). After the plasmids of target genes were transfected into A549 cells, the growth of antisense miRNA-224 and miRNA-122 a were inhibited, and the differences were significant as compared with the control group(P < 0.05). Besides, the inhibition of miRNA-122 a group was the most significant and there was statistically significant difference as compared with miRNA-224 group(t =-4.694, P = 0.009). After the plasmids of target genes were transfected into A549 cells, the proportion of apoptotic cells increased, the invasive cells were decreased and the clone ability reduced, and also there was a significant difference as compared with those of the control group(P < 0.05). What's more, the apoptotic peak appeared in miRNA-122 a group. Its invasion ability decreased most obviously(40.25 ± 3.97/visual field), the number of clone ability was 104.93 ± 4.87 and the inhibitory effect was the most obviously. There was statistically significant difference as compared with other groups(P < 0.05). Conclusions: A549 cells transfected by ultrasound microbubble-mediated antisense miRNA-224 and mi RNA-122 a plasmids possessed good transfection efficiency. The cell growth, invasion and colony forming abilities of transfected A549 cells were suppressed, which laid a solid foundation for the gene therapy of non-small cell lung cancer.
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Objective 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 liver parenchyma.Methods Perfluorocarbon(PFC)-containing microbubbles(ST68-PFC)were prepared by sonication based on surfactant(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the United Kingdom Department of Health, British Medical Research Council, Grant No. G99000178 and the United Kingdom National Health Service Research and Development Initiative
文摘AIM:To investigate the diagnosis of nonalcoholic steatohepatitis(NASH) using contrast ultrasonography in the NASH rat model.METHODS:The liver in methionine choline-deficient diet(MCDD) rats,a NASH model constructed by feeding an MCDD,was examined by contrast ultrasonography at weeks 2,4,8,12 and 16,with late phase images of contrast ultrasonography(Kupffer imaging) in which contrast enhancement was achieved by incorporation of a contrast agent by Kupffer cells(KCs),and images were compared to those in rats taking a regular chow.RESULTS:Decrease in contrast enhancement was observed first in MCDD rats at week 2.KCs were counted based on immunohistochemistry,but their numbers were not reduced and it was assumed that attenuation of contrast enhancement was attributable to reduced phagocytic activity of the KCs.CONCLUSION:It is suggested that clinical application of contrast ultrasonography may be valuable for noninvasive diagnosis of NASH.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11774088 and 11474090)the Hunan-Provincial Natural Science Foundation of China(Grant No.13JJ3076)the Science Research Program of Education Department of Hunan Province of China(Grant No.14A127)
文摘The goal of this article is to establish the conditions of excitation where one has to deal with ultrasound contrast agent(UCA) microbubbles pulsating near biological tissues with spherical boundary in ultrasound field for targeted drug delivery and cavitation-enhanced thrombolysis, etc., and contributes to understanding of mechanisms at play in such an interaction. A modified model is presented for describing microbubble dynamics near a spherical boundary(including convex boundary and concave boundary) with an arbitrary-sized aperture angle. The novelty of the model is such that an oscillating microbubble is influenced by an additional pressure produced by the sound reflection from the boundary wall. It is found that the amplitude of microbubble oscillation is positively correlated to the curve radius of the wall and negatively correlated to the aperture angle of the wall and the sound reflection coefficient. Moreover, the natural frequency of the microbubble oscillation for such a compliable wall increases with the wall compliance, but decreases with the reduction of the wall size, indicating distinct increase of the natural frequency compared to a common rigid wall. The proposed model may allow obtaining accurate information on the radiation force and signals that may be used to advantage in related as drug delivery and contrast agent imaging.
基金Supported by the High Technology Research Development Program of China(863 Program,No.2001AA218031)and the National Natural Science Foundation of China(No.30270404).
文摘Objective: To study on the preparation process of a new surfactant-based microbubble ultrasound contrast agent and to evaluate its contrast effects in vivo. Methods: Microbubble ultrasound contrast agent with three ester surfactants and other additives as its shell materials was prepared by sonication. Sulfur hexafluoride was adopted as the inner gas of the microbubbles. New methods through the combination of optical microscope and some softwares were used to measure the size distribution and the concentration of the microbubbles. Some parameters such as the pH value of the phosphate buffer, quantity of the carboxylic methyl cellulose in the shell materials, selection of the ultrasound power and process time, were studied. Six hybirded dogs were used to verify the in vivo contrast imaging of the contrast agent using second harmonic power Doppler modality. Safety and persistent time of the agent inner animal body were also investigated. Results: Ultrasound contrast agent prepared in the experiment had an average microbubble diameter of 3.95 microns with concentration of 3.6×109 microbubbles per millilitre. Carboxylic methyl cellulose was found as an important shell material which had obviously effect on the microbubble stability and production even with a little quantity. The buffer pH value also had a key role on the microbubble formation and the final production. When the buffer pH value reached 7.4, there was no microbubble produced. Under the approximate microbubble production, process time could be shorten with the increasing ultrasound power. The obvious ultrasound contrast imaging effects were detected in the dog's heart chamber and liver as well as kidney using only one millilitre agent when diluted. The agent was found safe to the dogs. At the same time, persistent time of the agent was found over 20 min in the dog's body. Conclusion: The new ultrasound contrast agent prepared in the experiment has high microbubble production and concentration, narrow microbubble size distribution ranging in several microns, well stability, little dosage needed in the contrast, well safety to the dogs and long persistent time, obvious contrast imaging effect in the dog's heart chamber, kidney and liver. These experiment data indicate that the new ultrasound contrast agent with three ester surfactants and carboxylic methyl cellulose as its main shell materials can be further developed for clinical purposes.
基金Supported by the National Natural Science Foundation of China(30270404)Specialized Research Fund for the Doctoral Program of Higher Education(2003069816)
文摘Objective: To present a self-developed experimental system for basic studies of blood perfusion imaging and time-intensity evaluating based on ultrasound contrast agent. Methods: The experimental system performed the image reconstruction and time-intensity processing with radio frequency signals. The system was comprised of ultra-high speed hardware data acquisition interface and low computational cost algorithms. The self-made contrast agent,blood mimic phantom and capillary phantom model were used to validate the experimental system. Results: The images acquired in blood phantoms with linear-array and curve-array transducers were given. The time-intensity curves corresponding to selected region of interested from image sequence were demonstrated. It was also shown the time-intensity based decay curves and a comparison of decay of ultrasound contrast agent under different ultrasound powers. Conclusion: Several experiments resulted from two in vitro phantom models show that the experimental system can be used to basic studies of blood perfusion and further clinical studies of microvasculature perfusion.
文摘Coded excitation is useful for ultrasound contrast imaging to increase penetration and SNR, and improve the contrast to tissue ratio (CTR). The waveform of bubble response depends greatly on bubble size, the frequency and bandwidth of the excitation chirp signal. This makes the pulse compression filter based on square-law be wrong for bubbles with changing sizes. In this paper, an adaptive pulse compression (APC) filter for the second harmonic of microbubble with varying size distribution is proposed. The APC filter is designed based on the estimated power spectrum of the received bubble harmonic echoes. Theoretical analysis and simulation studies are presented for evaluating performance of the APC filter. For monodisperse bubble, the power improvement factor of the APC filter can be more than 20 dB.
基金Projects supported by the National Natural Science Foundation of China(Grant Nos.81127901,81227004,11374155,11274170,11274176,11474001,11474161,11474166,and 11674173)the National High-Technology Research and Development Program,China(Grant No.2012AA022702)Qing Lan Project of Jiangsu Province,China
文摘Modelling and biomedical applications of ultrasound contrast agent(UCA) microbubbles have attracted a great deal of attention. In this review, we summarize a series of researches done in our group, including(i) the development of an all-in-one solution of characterizing coated bubble parameters based on the light scattering technique and flow cytometry;(ii) a novel bubble dynamic model that takes into consideration both nonlinear shell elasticity and viscosity to eliminate the dependences of bubble shell parameters on bubble size;(iii) the evaluation of UCA inertial cavitation threshold and its relationship with shell parameters; and(iv) the investigations of transfection efficiency and the reduction of cytotoxicity in gene delivery facilitated by UCAs excited by ultrasound exposures.
基金supported by the Hematopoietic Biorepository and Cellular Therapy Shared Resource of the Case Comprehensive Cancer Center(P30CA043703)the NIH grants T32GM007250,T32HL134622,,F30HL160111the National Institute of Biomedical Imaging and Bioengineering(R01EB025741,R01EB028144).
文摘Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer.These sub-micron particles are approximately 10x smaller than clinically available microbubbles.This allows them to effectively traverse compromised physiological barriers and circulate for extended periods of time.While various aspects of nanobubble behavior have been previously examined,their behavior in human whole blood has not yet been explored.Accordingly,herein we examined,for the first time,the short and long-term effects of blood components on nanobubble acoustic response.We observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline(PBS),plasma,or red blood cell solutions(RBCs).Specifically,after introducing nanobubbles to fresh human whole blood,signal enhancement,or the magnitude of nonlinear ultrasound signal,gradually increased by 22.8±13.1%throughout our experiment,with peak intensity reached within 145 s.In contrast,nanobubbles in PBS had a stable signal with negligible change in intensity(1.7±3.2%)over 8 min.Under the same conditions,microbubbles made with the same lipid formulation showed a56.8±6.1%decrease in enhancement in whole blood.Subsequent confocal,fluorescent,and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RBCs,suggesting that direct interactions,or hitchhiking,of nanobubbles on RBCs in the presence of plasma may be a possible mechanism for the observed effects.This phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery,where RBC interaction with nanoparticles could be exploited to improve delivery efficiency.
基金supported by the National Natural Science Foundation of China(No.32271470)National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-034)+1 种基金Beijing Natural Science Foundation(No.7212077)CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2021-I2M-1-058).
文摘Portal hypertension(PH)is a commonly observed syndrome in patients with cirrhosis and other chronic liver diseases(1).It is closely associated with severe clinical complications,including upper gastrointestinal hemorrhage,ascites,hepatic encephalopathy,and liver failure(2-6).Portal vein pressure(PVP)is a prognostic indicator for patients with cirrhosis,and PH is a contraindication for hepatectomy(7,8).Currently,the gold standard for assessing PVP is the measurement of PVP gradient[hepatic venous pressure gradient(HVPG)],which is indirectly determined by placing a catheter in the hepatic vein(3).
基金financially supported by National Project for Research and Development of Major Scientific Instruments(No.81727803)National Natural Science Foundation of China(No.82071980),State Key Program of National Natural Science of China(No.81930047)Projects of International Cooperation and Exchanges NSFC-PSF(No.31961143003).
文摘Microbubbles have been the earliest and most widely used ultrasound contrast agents by virtue of their unique features:such as non-toxicity,intravenous inject-ability,ability to cross the pulmonary capillary bed,and significant enhancement of echo signals for the duration of the examination,resulting in essential preclinical and clinical applications.The use of microbubbles functional-ized with targeting ligands to bind to specific targets in the bloodstream has further enabled ultrasound molecular imaging.Nevertheless,it is very challenging to utilize targeted microbubbles for molecular imaging of extra-vascular targets due to their size.A series of acoustic nanomaterials have been developed for breaking free from this constraint.Especially,biogenic gas vesicles,gas-filled protein nanostructures from microorganisms,were engineered as thefirst biomolecular ultrasound contrast agents,opening the door for more direct visual-ization of cellular and molecular function by ultrasound imaging.The ordered protein shell structure and unique gasfilling mechanism of biogenic gas vesicles endow them with excellent stability and attractive acoustic responses.What’s more,their genetic encodability enables them to act as acoustic reporter genes.This article reviews the upgrading progresses of ultrasound contrast agents from microbubbles to biogenic gas vesicles,and the opportu-nities and challenges for the commercial and clinical translation of the nascentfield of biomolecular ultrasound.
文摘Objective: To evaluate the curative effect of the Traditional Chinese Medicine (TCM) external therapy on knee osteoarthritis patients with different TCM constitutions using musculoskeletal ultrasonography and contrast-enhanced ultrasonography, and to explore the application value of contrast-enhanced ultrasonography in knee joint diseases. Methods: A total of 57 patients diagnosed with knee osteoarthritis in Shaanxi University of Traditional Chinese Medicine from December 2019 to May 2021 were collected, and they were divided into qi stagnation and blood stasis type group (23 cases) and cold-dampness obstruction type group (34 cases) according to the traditional Chinese medicine method. All patients were given acupuncture combined with TCM fumigation and washing. All patients underwent musculoskeletal ultrasonography and contrast-enhanced ultrasonography before and after treatment, observed and recorded relevant data, and compared the treatment effects between the two groups. Results: 85.96% (49/57) of knee osteoarthritis (KOA) patients had suprapatellar bursa effusion, 42.1% (24/57) had iliotibial band bursae effusion, some of which had poor sound transmission, and thickened synovium was seen in most effusions, 33.33% (19/57) had osteophyte formation. Compared with before treatment, the depth of suprapatellar sac effusion in the Qi stagnation and blood stasis type group decreased after treatment (P Conclusion: Musculoskeletal contrast-enhanced ultrasonography was used to quantitatively evaluate the efficacy of TCM external therapy on KOA for different TCM constitutions. Dynamic observation of synovial lesions of knee osteoarthritis provides a valuable imaging method for evaluating the efficacy of traditional Chinese medicine.
基金The authors thank Viviana Moroso(MSc,PhD)of MV Medical Writing(Luleå,Sweden)for copyediting the manuscript,and Dr.Clara Zichichi(Institute of Radiology,University of Udine)for having drawn Figure 1C.
文摘Kidney transplantation(KT)is an effective treatment for end-stage renal disease.Despite their rate has reduced over time,post-transplant complications still represent a major clinical problem because of the associated risk of graft failure and loss.Thus,post-KT complications should be diagnosed and treated promptly.Imaging plays a pivotal role in this setting.Grayscale ultrasound(US)with color Doppler analysis is the first-line imaging modality for assessing complications,although many findings lack specificity.When performed by experienced operators,contrast-enhanced US(CEUS)has been advocated as a safe and fast tool to improve the accuracy of US.Also,when performing CEUS there is potentially no need for further imaging,such as contrast-enhanced computed tomography or magnetic resonance imaging,which are often contraindicated in recipients with impaired renal function.This technique is also portable to patients’bedside,thus having the potential of maximizing the cost-effectiveness of the whole diagnostic process.Finally,the use of blood-pool contrast agents allows translating information on graft microvasculature into time-intensity curves,and in turn quantitative perfusion indexes.Quantitative analysis is under evaluation as a tool to diagnose rejection or other causes of graft dysfunction.In this paper,we review and illustrate the indications to CEUS in the post-KT setting,as well as the main CEUS findings that can help establishing the diagnosis and planning the most adequate treatment.
