Ultrasound contrast agents from microbubbles to biogenic gas vesicles

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.

Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

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.

Nano/microparticles and ultrasound contrast agents

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.

Nonlinear response of ultrasound contrast agent microbubbles:From fundamentals to applications

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.

Role of microbubble ultrasound contrast agents in the non-invasive assessment of chronic hepatitis C-related liver disease

长期地感染丙肝病毒的病人经常得长期的肝疾病，对肝损伤的严厉的评价在认为病毒的根除是治疗以前被要求。这篇文章检验从标准答案肝活体检视当前可得到的各种各样的评价方法到血清学的标记和成像。超声是在临床的实践的最广泛地使用的成像形式之一并且已经是为肝疾病的一个首要的诊断工具。Microbubble 超声对比代理人允许更高的分辨率要获得的图象和对要执行的微脉管的变化的功能的评价。在确定的这些代理人的角色肝的损害的状态作为与丙肝在病人决定肝疾病的阶段和等级的一个可行方法被讨论。尽管当前限制了到专家中心，提高对比的超声将不可避免地在临床的背景增加的微水泡的可获得性。

PREPARATION OF POLYELECTROLYTE MULTILAYER COATED MICROBUBBLES FOR USE AS ULTRASOUND CONTRAST AGENT

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.

Subharmonic and ultraharmonic emissions based on the nonlinear oscillation of encapsulated microbubbles in ultrasound contrast agents

Subharmonics or ultraharmonics provides better contrast-to-tissue ratio (CTR) than the fundamental or the second harmonics, having prospective application in medical diagnosis. In this paper, subharmonic and ultra-harmonic emissions are theoretically studied through nonlinear oscillation of encapsulated bubbles. The optimized frequencies for emissions of the subharmonics and ultra-harmonics are discussed. In addition, sound pressure de-pendences of the subharmonics and ultraharmonics are studied in theory as well as in measurement. Results reveal that the developments of both subharmonics and ultrahar-monics have the same trend, i.e. occurrence, growth and saturation, but the generation of ultraharmonic is a little earlier than that of subharmonic.

In vivo transfection of enhanced green fluorescent protein in rat retinal ganglion cells mediated by ultrasound-induced microbubbles

BACKGROUND： Studies have demonstrated that ultrasound-mediated microbubble destruction significantly improves transfection efficiency of enhanced green fluorescent protein （EGFP） in in vitro cultured retinal ganglial cells （RGCs）. OBJECTIVE： To investigate the feasibility of ultrasound-mediated microbubble destruction for EGFP transfection in rat RGCs, and to compare efficiency and cell damage with traditional transfection methods. DESIGN, TIME AND SETTING： In vivo, gene engineering experiment. The study was performed at the Central Laboratory, Institute of Ultrasonic Imaging, Chongqing Medical University from March to July 2008. MATERIALS： Eukaryotic expression vector plasmid EGFP and microbubbles were prepared by the Institute of Ultrasonic Imaging, Chongqing Medical University. The microbubbles were produced at a concentration of 8.7 × 10^11/L, with a 2-4 μm diameter, and 10-hour half-life in vitro. METHODS： A total of 50 Sprague Dawley rats were randomly assigned to four groups. Normal controls （n = 5） were infused with 5 μL normal saline to the vitreous cavity; the naked plasmid group （n = 15） was infused with 5 pL EGFP plasmid to the vitreous cavity; in the plasmid with ultrasound group （n = 15）, the eyes were irradiated with low-energy ultrasound wave （0.5 W/cm^2） for a total of 60 seconds （irradiated for 5 seconds, at 10-second intervals） immediately following infusion of EGFP plasmids to the vitreous cavities. In the microbubble-ultrasound group （n = 15）, the eyes were irradiated with the same power of ultrasonic wave immediately following infusion of microbubbles containing EGFP plasmids to the vitreous cavities. MAIN OUTCOME MEASURES： After 7 days, retinal preparations and EGFP expression in RGCs were observed by fluorescence microscopy. RGC quantification in the retinal ganglion cell layer was performed. In addition, EGFP mRNA expression was semi-quantitatively determined by RT-PCR. RESULTS： The transfection efficiency of EGFP to RGCs by microbubbles with ultrasound was significantly greater than the other groups, and no obvious damage was detected in the RGCs. CONCLUSION： Under irradiation of low-frequency ultrasound waves, ultrasound-mediated microbubble destruction was effective and resulted in safe transfection of the EGFP gene to the RGCs.

Characterization of the interaction of nanobubble ultrasound contrast agents with human blood components

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.

Subharmonic scattering of ultrasound contrast agent microbubbles may be an effective and promising tool for portal vein pressure estimation

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).

Interaction between encapsulated microbubbles:A finite element modelling study

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.

Novel ultrasound contrast agents——Biodegradable poly(lactic acid)microcapsules

As a novel ultrasound diagnostic contrast agent, the preparation, characterization and ultrasound imaging in the body of dog about poly(lactic acid) (PLLA) microcapsules have been studied. The behavior of this kind of contrast agent in the microcirculation was also investigated. Prepared by (water/oil/water) emulsion-solvent evaporation protocol, the PLLA microcapsules with hollow structure can enhance the ultrasound image both in vitro and in vivo, and the enduring time can last as long as 3 h. The microcirculation examination shows that the PLLA microcapsules with a diameter ranging from 2 to 8 mm could pass through the pulmonary capillaries without retention. All the results prove the PLLA microcapsules for potential use for the clinical application.

Modeling of ultrasound contrast agents bubble dynamics with modified surface tension coefficient

The current work proposes a model describing the dynamics of coated microbubbles, which simplifies the traditional three-layer model to a two-layer one by introducing a visco-elastic interface with variable surface tension coefficients to connect the gas zone and the liquid zone. In the modified model, the traditional two interfaces boundary conditions are combined into one to simplify the description of the bubble. Moreover, the surface tension coefficient is defined as a function of bubble radius with lower and upper limits, which are related to the buckling and rupture mechanisms of the bubble. Further discussion is made regarding the effects resulting from the change of the surface tension coefficient on bubble dynamics. The dynamic responses of Optison and Sonozoid microbubbles, measured experimentally based on light scattering technology (adapted from previously published work), are simulated using both classic three-layer models (e.g. Church's model) and simplified model. The results show that our simplified model works as well as the Church's model.

Gastrointestinal contrast-enhanced ultrasonography for diagnosis and treatment of peptic ulcer in children

BACKGROUND The detection rate of peptic ulcer in children is improving,with development of diagnostic procedures.Gastroscopy is the gold standard for the diagnosis of peptic ulcer,but it is an invasive procedure.Gastrointestinal contrast-enhanced ultrasonography(CEUS)has the advantages of being painless,noninvasive,nonradioactive,easy to use,and safe.AIM To investigate the clinical value of CEUS for diagnosis and treatment of peptic ulcer in children.METHODS We investigated 43 children with digestive tract symptoms in our hospital from January 2021 to June 2022.All children were examined by routine ultrasound,gastrointestinal CEUS,and gastroscopy.The pathological results of gastroscopy were taken as the gold standard.Routine ultrasonography was performed before gastrointestinal CEUS.Conventional ultrasound showed the thickness of the gastroduodenal wall,gastric peristalsis,and the adjacent organs and tissues around the abdominal cavity.Gastrointestinal CEUS recorded the thickness of the gastroduodenal wall;the size,location and shape of the ulcer;gastric peristalsis;and adjacent organs and tissues around the abdominal cavity.The results of routine ultrasound and gastrointestinal ultrasound were compared with those of gastroscopy to evaluate the diagnostic results and coincidence rate of routine ultrasound and gastrointestinal CEUS.All children received informed consent from their guardians for CEUS.This study was reviewed and approved by the hospital medical ethics committee.RESULTS Among the 43 children,17(15 male,2 female)were diagnosed with peptic ulcer by gastroscopy.There were 26 children with nonpeptic ulcer.There were eight cases of peptic ulcer and 35 of nonpeptic ulcer diagnosed by conventional ultrasound.The diagnostic coincidence rate of peptic ulcer in children diagnosed by conventional ultrasound was 79.1%(34/43),which was significantly different from that of gastroscopy(P=0.033).It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is low.Fifteen cases of peptic ulcer and 28 of nonpeptic ulcer were diagnosed by CEUS.The diagnostic coincidence rate of peptic ulcer in children was 95.3%(41/43).There was no significant difference between CEUS and gastroscopy(P=0.655).It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is high.CONCLUSION Gastrointestinal CEUS has a high coincidence rate in the diagnosis of peptic ulcer in children,and can be used as a preliminary examination method.

Role for contrast-enhanced ultrasound in assessing complications after kidney transplant

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.

Management of hepatocellular carcinoma: The role of contrast-enhanced ultrasound

Hepatocellular carcinoma(HCC)is the sixth most common neoplasm and the third cause of cancer death worldwide.Contrast enhanced ultrasound(CEUS)has been applied for more than ten years and plays increasingly important roles in the management of HCC.On the basis of the Guideline and Good Clinical Practice Recommendations for CEUS in the liver-update 2012and related literature about the management of HCC,we summarize the main roles and applications of CEUS in the management of HCC,including HCC surveillance,diagnosis,CEUS-guided treatment,treatment response evaluation and follow-up.The diagnostic algorithm for HCC is also suggested.Meanwhile,the comparisons between CEUS and contrast enhanced computed tomography/magnetic resonance imaging(CECT/CEMRI)in these areas are made.Although CEUS is subject to the same limitation as ordinary US and is inferior to CECT/CEMRI in some aspects,CEUS has proved to be of great value in the management of HCC with inher-ent advantages,such as sufficient high safety profile making it suitable for patients with renal failure or allergic to iodine,absence of radiation,easy reproducibility and high temporal resolution.The tremendous application of CEUS to the diagnosis and treatment of HCC provides more opportunities for patients with HCC diagnosed at different stages.

Evaluation of contrast-enhanced ultrasound for diagnosis of dysplastic nodules with a focus of hepatocellular carcinoma in liver cirrhosis patients

Objective： To compare the enhancement features of dysplastic nodnles with a focus of hepatocellular carcinoma （DN-HCC） versus HCC and regenerative nodules （RN） in cirrhotic patients. Methods： One hundred and ninety-three cirrhotic patients were enrolled in this study; they had 215 focal liver lesions, 1.0-3.5 cm in size, which were examined using contrast-enhanced ultrasound （CEUS） with SonoVue and diagnosed as HCC, RN or DN-HCC by biopsy. Samples were obtained using 18-gauge needles in the different enhanced areas. The enhancement features of DN-HCC, HCC and RN were evaluated. Results： There were 86 HCC lesions, 102 RN lesions, and 27 DN-HCC lesions diagnosed by biopsy. Of 86 HCC lesions, 87.2% （75/86） showed complete enhancement during the arterial phase, and 12.8% （11/86） had inhomogeneous enhancement, with no enhancement in the central area during the arterial phase; 100% （86/86） exhibited washout during the late phase. Of 102 RN lesions, 95.1% （97/102） had delayed or simultaneous enhancement during the arterial phase, and 4.9% （5/102） displayed slight enhancement during the arterial phase; 26.5% （27/102） exhibited washout and 73.5% （75/102） exhibited no washout during the late phase. In 27 DN-HCC lesions, only part of the lesions enhanced during the arterial phase and washed out during the late phase; the other areas had delayed or simultaneous enhancement during the arterial phase, and 29.6% （8/27） exhibited slight washout in the late phase. In 86 HCCs, the pathological feature was HCC in the enhanced area of 75 lesions, hepatocellular fatty degeneration in the slightly enhanced area of 7 lesions, and hepatocellular necrosis in the unenhanced area and HCC in the enhanced area of 4 lesions. In 102 RNs, the pathological diagnosis was hepatocyte proliferation with or without fatty degeneration. In 27 DN-HCCs, the pathological feature was HCC in the enhanced area and hepatocye regeneration in the unenhanced area. Conclusions： CEUS is useful for the diagnosis of focal liver lesions in cirrhotic patients. CEUS can help determine the progression from RN to DN-HCC to HCC by analyzing the hemodynamics. CEUS can promote the diagnostic accuracy of a biopsy by providing more accurate information on the site of the biopsy.

Contrast-enhanced harmonic endoscopic ultrasound imaging: Basic principles, present situation and future perspectives

Over the last decade, the development of stabilised microbubble contrast agents and improvements in available ultrasonic equipment, such as harmonic imaging, have enabled us to display microbubble enhancements on a greyscale with optimal contrast and spatial resolution. Recent technological advances made contrast harmonic technology available for endoscopic ultrasound(EUS) for the first time in 2008. Thus, the evaluation of microcirculation is now feasible with EUS, prompting the evolution of contrast-enhanced EUS from vascular imaging to images of the perfused tissue. Although the relevant experience is still preliminary, several reports have highlighted contrast-enhanced harmonic EUS(CHEUS) as a promising noninvasive method to visualise and characterise lesions and to differentiate benign from malignant focal lesions. Even if histology remains the gold standard, the combination of CH-EUS and EUS fine needle aspiration(EUS-FNA) can not only render EUS more accurate but may also assist physicians inmaking decisions when EUS-FNA is inconclusive,increasing the yield of EUS-FNA by guiding the puncture with simultaneous imaging of the vascularity.The development of CH-EUS has also opened up exciting possibilities in other research areas,including monitoring responses to anticancer chemotherapy or to ethanolinduced pancreatic tissue ablation,anticancer therapies based on ultrasound-triggered drug and gene delivery,and therapeutic adjuvants by contrast ultrasound-induced apoptosis.Contrast harmonic imaging is gaining popularity because of its efficacy,simplicity and noninvasive nature,and many expectations are currently resting on this technique.If its potential is confirmed in the near future,contrast harmonic imaging will become a standard practice in EUS.

Contrast-enhanced ultrasound in the biliary system:Potential uses and indications

Conventional ultrasound(US)is the first-line imaging investigation for biliary diseases.However,it is lack of the ability to depict the microcirculation of some lesions which may lead to failure in diagnosis for some biliary diseases.The use of contrast-enhanced US(CEUS)has reached the field of bile duct disease in recent years and promising results have been achieved.In this review,the methodology,image interpretation,enhancement pattern,clinical usefulness,and indications for CEUS in the biliary system are summarized.CEUS may be indicated in the biliary system under the following circumstances:(1)Where there is a need to make a characterization of intrahepatic cholangiocarcinoma(ICC);(2)For differentiation diagnosis between ICC and other tumors(i.e.hepatocellular carcinoma or liver metastasis)or infectious diseases;(3)For differentiation diagnosis between biliary cystadenoma and biliary cystadenocarcinoma;(4)To detect malignant change in Caroli’s disease;(5)To depict the extent of Klatskin’s tumor with greater clarity;(6)To make a distinction between gallbladder cholesterol polyp,adenoma and polypoid cancer;(7)To make a distinction between chronic cholecystitis with thickened wall and gallbladder cancer;(8)For differentiation diagnosis between motionless sludge and gallbladder cancer;(9)For differentiation diagnosis between common bile duct cancer and sludge or stone without acoustic shadowing;and(10)In patients who are suspected of having a drop of their percutaneous transhepatic cholangiodrainage tube,US contrast agent can be administered to through the tube detect the site of the tube.

Application of ultrasound contrast in identification and diagnosis of ocular spaceoccupying lesions

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.