脉冲占空比对磁性微泡介导的聚焦超声温升效应的影响

集合多种诊断和治疗功能的声/磁造影剂微泡的研究与开发已经成为当前医学超声、生物医学工程及临床应用领域共同关注的热点问题.超顺磁氧化铁纳米颗粒具有独特的磁性特征和良好的生物相容性,可被用作核磁共振造影剂来提升影像对比度、空间分辨率及临床诊断准确性.我们的前期工作表明,通过将超顺磁氧化铁纳米颗粒挂载于常规超声造影剂微泡表面,可以成功构建多模态诊断及治疗介质,显著改变超声造影剂微泡的尺度分布及包膜粘弹系数等物理特性,进而影响微泡造影剂的声散射特性及其声空化效应和热效应.然而,此前的研究仅考虑了声场强度和微泡浓度等影响因素,对于脉冲超声时间特性对磁性微泡造影剂动力学响应的影响的相关研究仍有所欠缺.本文通过热电偶对凝胶仿体血管模型中流动的双模态磁性微泡在不同占空比超声脉冲信号作用下,产生温升效应开展了系统的实验测量,并基于有限元模型对实验结果进行了仿真验证.结果显示,脉冲信号占空比的提升是增强血管中磁性微泡在聚焦超声作用下温升效果的关键性时间影响因素.本文的研究成果将有助于更好地理解不同超声作用参数对双模态磁性微泡的热效应的影响机制,对保障双模态磁性微泡在临床热疗应用中的安全性和有效性具有重要的...     

包膜黏弹特性及声驱动参数对相互作用微泡动力学行为的影响

关于多气泡相互作用的理论研究对于深入理解超声造影剂在医疗领域中的应用机理具有重要意义。本工作建立了一个2维轴对称有限元模型来研究流体环境中超声造影剂双气泡相互作用,讨论了驱动超声频率和气泡尺寸对气泡之间吸引和排斥趋势的影响,得到了气泡半径与气泡之间距离随时间变化的曲线,以及气泡周围流体速度场的细节,并且研究了气泡包膜参数(即表面张力系数和粘度系数)对气泡相互作用的影响.结果表明,相互作用中的气泡对整体的相对运动趋势由驱动频率和共振频率之间的关系决定;在超声参数固定时,气泡包膜的粘弹特性可用来调控气泡间相互作用强度。结果对实验中观察到的气泡聚集现象进行了合理解释,并为超声造影剂在医疗实践中的应用提供了基础理论支撑.      

Study on shock wave-induced cavitation bubbles dissolution process

This study investigated dissolution processes of cavitation bubbles generated during in vivo shock wave(SW)-induced treatments. Both active cavitation detection(ACD) and the B-mode imaging technique were applied to measure the dissolution procedure of bi Spheres contrast agent bubbles by in vitro experiments. Besides, the simulation of SW-induced cavitation bubbles dissolution behaviors detected by the B-mode imaging system during in vivo SW treatments, including extracorporeal shock wave lithotripsy(ESWL) and extracorporeal shock wave therapy(ESWT), were carried out based on calculating the integrated scattering cross-section of dissolving gas bubbles with employing gas bubble dissolution equations and Gaussian bubble size distribution. The results showed that(i) B-mode imaging technology is an effective tool to monitor the temporal evolution of cavitation bubbles dissolution procedures after the SW pulses ceased, which is important for evaluation and controlling the cavitation activity generated during subsequent SW treatments within a treatment period;(ii) the characteristics of the bubbles, such as the bubble size distribution and gas diffusion, can be estimated by simulating the experimental data properly.     

Impact of cavitation on lesion formation induced by high intensity focused ultrasound

High intensity focused ultrasound(HIFU) has shown a great promise in noninvasive cancer therapy. The impact of acoustic cavitation on the lesion formation induced by HIFU is investigated both experimentally and theoretically in transparent protein-containing gel and ex vivo liver tissue samples. A numerical model that accounts for nonlinear acoustic propagation and heat transfer is used to simulate the lesion formation induced by the thermal effect. The results showed that lesions could be induced in the samples exposed to HIFU with various acoustic pressures and pulse lengths. The measured areas of lesions formed in the lateral direction were comparable to the simulated results, while much larger discrepancy was observed between the experimental and simulated data for the areas of longitudinal lesion cross-section. Meanwhile,a series of stripe-wiped-off B-mode pictures were obtained by using a special imaging processing method so that HIFUinduced cavitation bubble activities could be monitored in real-time and quantitatively analyzed as the functions of acoustic pressure and pulse length. The results indicated that, unlike the lateral area of HIFU-induced lesion that was less affected by the cavitation activity, the longitudinal cross-section of HIFU-induced lesion was significantly influenced by the generation of cavitation bubbles through the temperature elevation resulting from HIFU exposures. Therefore, considering the clinical safety in HIFU treatments, more attention should be paid on the lesion formation in the longitudinal direction to avoid uncontrollable variation resulting from HIFU-induced cavitation activity.     

Noninvasive treatment efficacy monitoring and dose control for high-intensity focused ultrasound therapy using relative electrical impedance variation

As an effective therapeutic modality, high-intensity focused ultrasound(HIFU) can destroy tumour tissues by thermocoagulation with less metastasis, but it is still limited by inaccurate non-invasive temperature monitoring and efficacy evaluation. A model of electrical impedance measurement during HIFU therapy was established using the temperatureimpedance relationship. Based on the simulations of acoustic pressure, temperature, and electrical conductivity, the impedance of the phantom was calculated and experimentally demonstrated for different values of acoustic power values and treatment time. We proved that the relative impedance variation(RIV) increases linearly with the increasing treatment time at a fixed acoustic power, and the relative impedance variation rate shows a linear relationship with the acoustic power.The RIV and treatment time required for HIFU treatment efficacy are inversely proportional to the acoustic power and the square of acoustic power, respectively. The favourable results suggest that RIV can be used as an efficient indicator for noninvasive temperature monitoring and efficacy evaluation and may provide new strategy for accurate dose control of HIFU therapy.     

超声空化增强川芎嗪对脑缺血再灌注损伤保护作用机制的研究

川芎的生物活性成分(川芎嗪)已广泛应用于治疗心脑血管疾病。基于谷氨酸诱导PC12细胞损伤建立脑缺血再灌注损伤的细胞模型,探讨超声增强川芎嗪对谷氨酸损伤PC12细胞的保护作用机制。研究结果表明,超声能进一步加强川芎嗪对细胞的保护,其主要作用机制为:(1)抑制氧化应激和细胞凋亡相关的Bcl-2蛋白和Bax蛋白的变化从而达到抗凋亡的效果;(2)降低炎症因子(TNF-α和IL-8)的表达,减轻炎症反应损伤;(3)适当的声压可以增强川芎嗪对谷氨酸损伤PC12细胞的保护作用,但过高的声压会引起细胞损伤,导致细胞凋亡。本文的工作表明超声能够增强川芎嗪对脑缺血再灌注损伤的保护作用,为临床脑缺血再灌注损伤的治疗提供了新治疗策略。      

超声造影剂微气泡的包膜黏弹特性的定量表征研究

包膜黏弹特性显著影响微气泡超声造影剂的诊断及治疗应用效果. 本文结合原子力显微镜技术及声衰减特性测量提出了一种对微气泡造影剂包膜黏弹特性定量表征的新方法. 首先采用原子力显微镜技术进行机械特性分析得到包膜微气泡的有效硬度及体弹性模量; 然后测量声衰减特性, 基于微气泡动力学理论, 计算包膜微气泡的体黏度系数. 为验证方法的有效性, 实验制备了直径为1-5 μm的白蛋白包膜微气泡造影剂, 原子力显微镜测量的有效硬度和体弹性模量分别为0.149±0.012 N/m和8.31±0.667 MPa, 并与粒径无关. 声衰减特性测量和动力学理论拟合的包膜微气泡的体黏度系数为0.374±0.003 Pa·s. 该方法可推广至其他种类包膜微气泡的黏弹特性表征, 对超声造影剂的制备及其诊断和治疗应用有积极意义.     

超声增强藻酸钙凝胶支架材料孔隙率的研究

藻酸钙凝胶具有三维立体多孔结构, 能为细胞生长提供充分的附着空间, 且具有良好的生物相容性和一定的机械强度, 是一种理想的细胞支架材料. 本文研究了藻酸钙三维支架材料的力学特性与氯化钙/藻酸钠的配比的关系, 并提出采用低强度脉冲超声处理藻酸钙凝胶、基于超声空化效应增强藻酸钙凝胶孔隙率的新方法. 实验采用交联合成方法制备藻酸钙凝胶支架材料, 测量力学特性、孔洞的联通性与孔隙率, 并利用绿色荧光蛋白的表达评价细胞的增殖能力. 结果表明, 当氯化钙/藻酸钠的配比为3:5时, 凝胶的机械强度和弹性较好, 力学性能稳定, 为最佳配比参数. 采用声压0.055 MPa的脉冲超声作用20 min, 可以有效提高凝胶支架的孔隙率; 且细胞在该支架中生长状态良好, 呈现团簇状生长趋势.     

Real-Time Measurements and Modelling on Dynamic Behaviour of SonoVue Bubbles Based on Light Scattering Technology

The dynamic behaviour of SonoVue microbubbles, a new generation ultrasound contrast agent, is investigated in real time with light scattering method. Highly diluted SonoVue microbubbles are injected into a diluted gel made of xanthan gum and water. The responses of individual SonoVue bubbles to driven ultrasound pulses are measured. Both linear and nonlinear bubble oscillations are observed and the results suggest that SonoVue microbubbles can generate strong nonlinear responses. By fitting the experimental data of individual bubble responses with Sarkar＇s model, the shell coating parameter of the bubbles and dilatational viscosity is estimated to be 7.0 nm-s-Pa.     

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(2 D) 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.