Correlation study of biological characteristics of non-small cell lung cancer A549 cells after transfecting plasmid by microbubble ultrasound contrast agent

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.

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

Patients who are chronically infected with the hepatitis C virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This article examines the various assessment methods currently available from gold standard liver biopsy to serological markers and imaging. Ultrasound is one of the most widely used imaging modalities in clinical practice and is already a first-line diagnostic tool for liver disease. Microbubble ultrasound contrast agents allow higher resolution images to be obtained and functional assessments of microvascular change to be carried out. The role of these agents in quantifying the state of hepatic injury is discussed as a viable method of determining the stage and grade of liver disease in patients with hepatitis C. Although currently confined to specialist centres, the availability of microbubble contrast-enhanced ultrasound will inevitably increase in the clinical setting.

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

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.

Dynamics of an ultrasound contrast agent microbubble near spherical boundary in ultrasound field

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.

Microbubble ultrasound contrast agent with three esters and carboxylic methyl cellulose as main shell materials: Its preparation and imaging evaluation

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.

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.

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.

The combined time-frequency analysis of the acoustic signals backscattered from ultrasonic contrast agents in the evaluation of the blood perfusion

Objective: To analyze the non-periodic, unstable and even chaotic echoes scattered from microbubbles which are extremely sensitive and may easily collapse, fragment or shrink when ultrasound contrast agents are exposed to ultrasound (US) irradiation. Methods: The combined time-frequency analysis was applied to the original signals instead of the traditional Fourier spectral analysis technique. Results: The results obtained from simulation as well as experiment showed that the subharmonic, 2nd harmonic and ultra harmonic of the microbubbles occurred during the oscillation and varied with time. The dependence on the incident ultrasonic amplitude and microbubble parameters were established. Conclusion: The transient echoes backscattered from the ultrasound agent in the evaluation of the blood perfusion can be analyzed thoroughly by the technique of combined-frequency analysis and the time detail of the frequency contents can be revealed.

Basic physical, acoustic properties, and in vitro ultrasound imaging enhancement of the lipid-coated microbubbles

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.

Value of contrast-enhanced intraoperative ultrasound for cirrhotic patients with hepatocellular carcinoma:A report of 20 cases

AIM： To assess the clinical value of contrast-enhanced intraoperative ultrasound （CE-IOUS） as a novel tool in partial hepatectomy for cirrhotic patients with hepatocellular carcinoma （HCC）. METHODS： From January 2007 to September 2007, a total of 20 consecutive cirrhotic patients with HCC scheduled to undergo partial hepatectomy were studied. Preoperative contrast enhanced computer tomography （CT） and/or magnetic resonance （MR） scans were performed within 1-2 wk before operation. Intraoperative ultrasound （IOUS） and CE-IOUS were carried out after mobilization of the liver. Lesions on precontrast and postcontrast scans were counted and mapped. CE-IOUS was performed with intravenous injection of ultrasound contrast agents SonoVue （Bracco Imaging, Milan, Italy）. Arterial, portal and late phases of contrast enhancement were recorded and analyzed. Nodules showing arterial phase hyper-enhancing and/or hypo-enhancing in late parenchymal phase were considered malignant and removed surgically. Ultrasound-guided biopsy and ethanol ablation would be an option if the nodule could not be removed surgically. Newly detected nodules on IOUS showing iso-enhancement in both arterial and late phases were considered benign. These nodules were either removed surgically if they were close to the main lesion or followed by examinations of alpha-fetoprotein （AFP） level and ultrasound and/or CT/MR every 3 too. RESULTS： IOUS found 41 nodules in total, among which 17 （41.46%） were newly detected compared to preoperative imaging. Thirty-three nodules were diagnosed malignant by CE-IOUS, including one missed by IOUS. The sensitivity and specificity of CE-IOUS on detecting HCC nodules are 100% （33/33 and 100% （9/9）, respectively. Nine nodules were considered benign by CE-IOUS, four was confirmed at histology and five by follow-up. CE-IOUS changed the surgical strategy in 35% （7/20） of patients and avoid unnecessary intervention in 30% （6/20） of patients. CONCLUSION： CE-IOUS is a useful means to characterize the nodules detected by IOUS in cirrhotic liver, to find isoechoic HCC nodules which can not be shown on IOUS and to improve the accuracy of conventional IOUS, thus it can be used as an essential tool in the surgical treatment of cirrhotic patients with HCC.

Use of second generation contrast-enhanced ultrasound in the assessment of focal liver lesions

Ultrasound (US) is often the first imaging modality employed in patients with suspected focal liver lesions. The role of US in the characterisation of focal liver lesions has been transformed with the introduction of specific contrast media and the development of specialized imaging techniques. Ultrasound now can fully characterise the enhancement pattern of hepatic lesions, similar to that achieved with contrast enhanced multiphasic computed tomography (CT) and magnetic resonance imaging (MRI). US contrast agents are safe, well-tolerated and have very few contraindications. Furthermore, real-time evaluation of the vascularity of focal liver lesions has become possible with the use of the newer microbubble contrast agents. This article reviews the enhancement pattern of the most frequent liver lesions seen, using the second generation US contrast media. The common pitfalls for each type of lesion are discussed. The recent developments in US contrast media and specific imaging techniques have been a major advance and this technique, in view of the intrinsic advantages of US, will undoubtedly gain popularity in the years to come.

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.

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.

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.

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.

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.

不同包膜材料的超声造影剂微泡的瞬态空化阈值研究

该文研究2种商用超声造影剂Optison和SonoVue微泡的空化声压阈值随微泡体积比浓度和激励超声脉冲宽度变化的规律。结果显示,①随着微泡浓度或激励超声脉冲宽度的增加,2种微泡的空化声压阈值均会降低;②相比Optison微泡,SonoVue微泡具有更薄的磷脂包膜和更高的单位体积空化核数目,因此具有更低的空化声压阈值和更强的空化强度。通过选择恰当的微泡特性参数和超声激励参数,可以有效调节和利用造影剂微泡的声空化效应,为超声医学成像和治疗的临床应用提供优化方案。

携单抗载增效剂超声纳米微泡制备实验的探索与研究

目的超声纳米微泡造影剂可携带药物在实现精准成像的同时定向到达目标微环境实现靶向给药。探索制备携单抗超声纳米微泡造影剂的实验条件及验证方式。方法通过乳化法制备超声纳米微泡并用链霉亲和素对其进行修饰;再通过生物素-亲和素系统与被生物素化的帕博利珠单抗(PD-1单抗)进行连接,得到携PD-1单抗载增效剂超声纳米粒;探索高效率的实验条件及验证方式;对实验制得超声纳米微泡的基本性质和实验表征分别进行检测与分析;对纳米微泡进行体外相变及超声显像效果的初步验证。结果成功制备出以高分子聚合物聚乳酸羟基乙酸包载液态氟碳和血卟啉单甲醚、同时用PD-1单抗修饰其表面的携单抗载增效剂超声纳米微泡;血卟啉单甲醚与聚乳酸羟基乙酸的比例在1∶25左右时饱和状态良好,血卟啉单甲醚的包封率为40.4%;吗啉乙磺酸缓冲溶液(MES Buffer)pH=7.4时血卟啉单甲醚的包封状态及聚乳酸羟基乙酸壳膜与链霉亲和素的结合效率可以取得较好的平衡;纳米微泡及链霉亲和素修饰后的生物素化单抗在激光共聚焦显微镜下分别表现出红色和绿色荧光,叠加融合后呈现黄色荧光,间接表明携PD-1单抗载增效剂纳米微泡制备成功;纳米微泡复溶后水溶性及分散度较好,基于其较稳定的物理性质,4℃条件下可短期保存;纳米微泡在扫描电子显微镜下表现为表面光整的类球形结构,大小整体较均匀,局部可见小范围粘连聚集现象;透射电子显微镜下纳米微泡呈内部黑色的类球形结构;动态激光散射仪测得纳米微泡平均粒径为(322.29±83.56)nm,Zeta电位为(-2.41±1.75)mV,聚合物分散指数约为0.287。纳米微泡在40℃左右时开始出现相变表现,一定温度范围(40℃~50℃)内有较好的超声显像效果,但分散性欠佳。结论成功制备出携单抗载增效剂超声纳米微泡;纳米微泡整体大小较均匀,局部存在粘连聚集现象;一定温度范围内可发生相变,体外超声显像效果较好,分散均匀度欠佳。

微泡超声造影剂辅助高强度聚焦超声治疗子宫腺肌症的有效性和安全性分析

目的分析微泡超声造影剂辅助高强度聚焦超声(HIFU)治疗子宫腺肌症的有效性和安全性。方法选取2020年7月至2021年7月宜春市妇幼保健院妇产科收治的80例子宫腺肌病患者作为研究对象,所有患者随机编号后按照奇偶数分为对照组与研究组,每组40例。两组均应用HIFU治疗,研究组在术前注射微泡超声造影剂辅助治疗。比较两组手术指标、临床指标、不良反应发生情况、女性性生活指数量表(FSFI)评分、Olson婚姻质量问卷(ENRIC)评分。结果研究组治疗时间、高能聚焦时间、出现团块灰度时间均短于对照组,差异有统计学意义(P<0.05);两组消融分数比较差异无统计学意义。治疗后,研究组子宫体积小于对照组,月经量少于对照组,差异有统计学意义(P<0.05);两组病灶体积、痛经程度评分比较差异无统计学意义。研究组治疗区域疼痛发生率为52.50%,低于对照组的80.00%,差异有统计学意义(P<0.05);两组臀部疼痛、神经疼痛、腿部疼痛、肛门坠胀、皮肤不适、下腹疼痛、阴道血性分泌物、发热、骶尾部疼痛、腹胀发生率比较差异无统计学意义。治疗后3个月,两组FSFI、ENRIC评分均高于治疗前,差异有统计学意义(P<0.05),但组间比较差异无统计学意义。结论微泡超声造影剂辅助HIFU治疗子宫腺肌症可缩短高能聚焦时间、出现团块灰度时间及治疗时间,改善患者临床症状,降低术中不良反应发生率,提高患者性生活及婚姻质量,值得临床推广应用。

基于表面活性剂的纳米包膜微泡超声造影剂

采用声空化的方法 ,以 3种酯类表面活性剂作为微泡的纳米包膜材料进行了静脉注射微泡超声造影剂的制备研究 ,实验研究了超声功率与超声时间的选择、磷酸盐缓冲溶液 pH值对微泡产量的影响、通气方式的选择、稀释液对微泡流动性的影响、振动对微泡的影响 ,研究了微泡的保存方式 ,并对制备出的微泡超声造影剂进行了体外及动物体内造影成像效果研究 ,给出了实验犬肾脏造影灌注的结果 .