超声脉冲长度与重复频率对流动微泡群稳态空化特性的影响

为了深入理解超声脉冲长度(PL)与重复频率(PRF)对流动微泡群稳态空化特性的影响,本研究自行制备仿体血管,利用注射泵推动微泡群在其中恒速流动,使用1 MHz的聚焦换能器激励微泡群产生稳态空化,另一个7.5 MHz的平面换能器接收声信号,经前置放大及高速采集后送至上位机存储。在定义临界重复频率(Critical PRF,CPRF)的基础上,通过深入的时频域分析,我们发现PL和PRF共同决定流动微泡群的稳态空化特性:当PRF低于CPRF时,流动微泡群的稳态空化剂量(Stable Cavitation Dose,SCD)与PL呈正相关,且时域分布均匀;而当PRF大于CPRF时,其稳态空化特性由PL决定,在长PL (＞100μs)下,SCD随着PL增加逐渐减小,且时域分布不均匀;在短PL (＜50μs)下,SCD和PRF无显著相关关系,且时域分布均匀。本研究结果深入阐明了流动微泡群的稳态空化特性,期望可用其获取可预测可控的生物效应,并应用于相关临床治疗。      

脉冲超声激励下SonoVue微泡的瞬态空化特性

将SonoVue微泡从临床疾病诊断拓展至治疗引起了诸多研究人员的兴趣。为了平衡治疗效率和生物安全性,深入理解声学参数和SonoVue微泡瞬态空化的关系至关重要。本研究自行制备仿体容器放置SonoVue微泡,使用1 MHz发射换能器激励其产生空化效应,另一个7.5 MHz的聚焦换能器接收声信号,经放大及高速数据采集后送上位机处理。通过深入分析信号的时频域特征,我们提出以宽带信号的能量及其随时间变化曲线的半高宽来表征瞬态空化的剂量(ICD)和相对持续时间(ICP),并确定:瞬态空化的发生和ICD依赖于峰值负声压,但ICP随峰值负声压的增加而减小;脉冲重复频率和脉冲持续时间都和ICD及ICP正相关;且脉冲持续时间的影响较大。这些结果有望为SonoVue微泡的治疗应用提供理论支持。      

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...     

线性啁啾脉冲频域-时域相移转换的模拟研究

在超快激光与物质相互作用的实验中, 实现单束实时的频谱干涉测量对提高测量精度很重要。基于频谱干涉原理和线性啁啾脉冲瞬时频率与时间的线性关系对啁啾脉冲频域相移直接映射为瞬态时域相移的原理进行了理论研究; 推导出这种频域-时域相移映射模式成立的限制条件。对相移直接映射过程进行了数值模拟和分析, 结果显示, 该方法可以得到具有瞬态特性的时域相移, 具有单束测量的能力; 在微扰和带宽一定的条件下, 增加探测脉冲的啁啾量, 可以减小频域-时域相移映射过程中产生的误差。     

高强度聚焦超声场中空化泡群的结构及其形成过程

空化是高强度聚焦超声(HIFU)引起组织损伤的作用机制之一。本文使用高速摄影技术研究了HIFU场中空化泡群结构的空间分布特征、超声功率对空化泡群结构的影响、空化泡群结构的建立过程尤其是起始过程。空化泡群的结构以空化泡在声场中的区域化分布为特征．在一定功率范围内空化泡群的结构保持稳定。从建立过程来看,空化泡群首先出现在焦区,然后在焦后区(远离换能器的区域)形成,焦前区(靠近换能器的区域)空化泡群最后形成。在对空化泡群起始的研究中发现最初拍摄到的空化泡群形状与焦区形状接近,并且观察到空化泡在焦区发生聚集然后破裂的现象。     

超声波声孔效应中气泡动力学的研究

在超声快速制取组织细胞病理切片的过程中，发现激励信号对切片制取效果有明显的影响.为了掌握超声激励信号对组织细胞的影响规律，达到快速制取病理切片的最佳状态，从气泡空化模型入手，通过改变激励信号频率、声压、气泡初始半径和液体黏滞系数等参量，研究了声孔效应中气泡动力学激励机制.数值计算表明：空化泡振动随激励声压增强而升高，随液体黏滞系数增强而减弱；一定频率范围内空化泡振动能保持在膨胀、收缩和振荡的稳定空化状态，存在空化泡稳态振动的最佳激励频率；一定初始半径能保证空化泡产生稳定的振动，存在空化泡稳态振动幅度最大的初始半径.实际操作中，在频率、声压、初始半径和黏滞系数综合作用的若干空化阈内，声孔效应使超声快速法制取细胞组织切片获得最佳效果. 关键词： 声孔效应 超声空化 气泡振动 稳态空化域     

亚临界水中超声激励空化泡动力学分析

考察亚临界水中压力和温度对超声空化泡动力学的影响。应用非线性Rayleigh-Plesset方程模拟空化泡运动过程,并利用Matlab软件编程求数值解,用碘量法测定超声在亚临界水中的声空化产额。结果表明:当亚临界水的压力相似文献   

纳米包膜造影微泡在脉冲超声场中的瞬态非线性特性研究

对包膜造影微泡的研究中,使用的基本上都是单泡模型。但是一般实验均是针对微泡群设计的;同时对微泡背向散射信号的分析采用的都是传统的谱分析。本文中严格控制实验条件,获得了单个微泡在脉冲超声场中的背向散射回波信号;然后经短时傅里叶变换,研究了微泡的瞬态非线性特性,揭示了微泡振动中非线性谐波随着时间的变化情况,是此前相关工作中未见报告的.     

流体控制方程的超声空化泡动力学模拟*

本文基于流体动力学控制方程和VOF模型,在FLUENT 14.5软件环境下对超声空化泡进行数值模拟。首先研究了超声空化泡一个周期内的形态变化,并且利用空化泡形态变化的最大面积、最小面积、膨胀时间、收缩时间等数值结果分析超声参数对空化效果的影响。同时探究了双频超声作用下空化泡运动的变化,计算结果表明:在其他条件相同的情况下,在1~5MPa范围内,超声声压幅值为3MPa时空化效果最好;当超声频率大于20kHz时,空化效果随着超声频率的增大而降低。对于频率相同的双频超声,较声压幅值为其两倍的单频超声有更好的空化效果;对于频率不同的双频超声,空化效果受到频率差的影响。     

超声波作用下泡群的共振声响应

从球状泡群气泡动力学方程出发, 考虑泡群间次级声辐射的影响, 得到了声场中两泡群共同存在时气泡振动的动力学方程, 并以此为基础探讨声波驱动下双泡群振动系统的共振响应特征. 由于泡群间气泡间的相互作用, 系统存在低频共振和高频共振现象, 两不同共振频率的数值与泡群内气泡的本征频率相关. 泡群内气泡的本征频率又受到初始半径、泡群大小和泡群内气泡数量的影响. 气泡自由振动和驱动声波的耦合激起泡群内气泡的受迫振动, 气泡初始半径、气泡数密度和驱动声波频率等都会影响泡群内气泡的振动幅值和初相位. 关键词： 气泡群 共振 声响应 超声空化     

Improving temporal stability of stable cavitation activity of circulating microbubbles using a closed-loop controller based on pulse-length regulation

Stable cavitation (SC) has shown great potential for novel therapeutic applications. The spatiotemporal distribution of the SC activity of microbubbles circulating in a target region is not only correlated with the uniformity of treatment, but also with some undesirable effects. Therefore, it is important to achieve controllable and desirable SC activity in target regions for improved therapeutic efficiency and biosafety. This study proposes a closed-loop feedback controller based on pulse length (PL) regulation to improve the temporal stability of SC activity. Microbubbles circulating in a physiological flowing phantom were exposed to a 1 MHz focused transducer. The SC signals produced were initially received by another 7.5 MHz plane transducer, followed by high-speed signal acquisition and real-time processing. Based on the real-time-measured SC intensity excited by the current acoustic pulse, the proposed closed-loop feedback controller used three proportional coefficients to regulate the peak negative pressure (PNP) and PL of the next acoustic pulse during the acceleration and stable stages, respectively. The results show that the rise time and the temporal stability of the SC intensity of the microbubbles circulating in these two stages were improved significantly by the optimized proportional coefficients used in the proposed controller. Importantly, when compared with the traditional closed-loop feedback controller based on PNP regulation, the proposed closed-loop feedback controller based on PL regulation reduced the probability of a transition between stable and inertial cavitation, thus avoiding the risk of disadvantageous bioeffects in practical applications. These results demonstrate the effectiveness of the proposed PL-based closed-loop feedback controller and provide a feasible strategy for realization of controllable cavitation activity in applications.     

Harmonic responses and cavitation activity of encapsulated microbubbles coupled with magnetic nanoparticles

Encapsulated microbubbles coupled with magnetic nanoparticles, one kind of hybrid agents that can integrate both ultrasound and magnetic resonance imaging/therapy functions, have attracted increasing interests in both research and clinic communities. However, there is a lack of comprehensive understanding of their dynamic behaviors generated in diagnostic and therapeutic applications. In the present work, a hybrid agent was synthesized by integrating superparamagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles (named as SPIO-albumin microbubbles). Then, both the stable and inertial cavitation thresholds of this hybrid agent were measured at varied SPIO concentrations and ultrasound parameters (e.g., frequency, pressure amplitude, and pulse length). The results show that, at a fixed acoustic driving frequency, both the stable and inertial cavitation thresholds of SPIO-albumin microbubble should decrease with the increasing SPIO concentration and acoustic driving pulse length. The inertial cavitation threshold of SPIO-albumin microbubbles also decreases with the raised driving frequency, while the minimum sub- and ultra-harmonic thresholds appear at twice and two thirds resonance frequency, respectively. It is also noticed that both the stable and inertial cavitation thresholds of SonoVue microbubbles are similar to those measured for hybrid microbubbles with a SPIO concentration of 114.7 μg/ml. The current work could provide better understanding on the impact of the integrated SPIOs on the dynamic responses (especially the cavitation activities) of hybrid microbubbles, and suggest the shell composition of hybrid agents should be appropriately designed to improve their clinical diagnostic and therapeutic performances of hybrid microbubble agents.     

Intensified and controllable vaporization of phase-changeable nanodroplets induced by simultaneous exposure of laser and ultrasound

Phase-changeable contrast agents have been proposed as a next-generation ultrasound contrast agent over conventional microbubbles given its stability, longer circulation time and ability to extravasate. Safe vaporization of nanodroplets (NDs) plays an essential role in the practical translation of ND applications in industry and medical therapy. In particular, the exposure parameters for initializing phase change as well as the site of phase change are concerned to be controlled. Compared to the traditional optical vaporization or acoustic droplet vaporization, this study exhibited the potential of using simultaneous, single burst laser and ultrasound incidence as a means of activating phase change of NDs to generate cavitation nuclei with reduced fluence and sound pressure. A theoretical model considering the laser heating, vapor cavity nucleation and growth was established, where qualitative agreement with experiment findings were found in terms of the trend of combined exposure parameters in order to achieve the same level of vaporization outcome. The results indicate that using single burst laser pulse and 10-cycle ultrasound might be sufficient to lower the exposure levels under FDA limit for laser skin exposure and ultrasound imaging. The combination of laser and ultrasound also provides temporal and spatial control of ND vaporization and cavitation nucleation without altering the sound field, which is beneficial for further safe and effective applications of phase-changeable NDs in medical, environmental, food processing and other industrial areas.     

Effect of polymer surface activity on cavitation nuclei stability against dissolution

The persistence of acoustic cavitation in a pulsed wave ultrasound regime depends upon the ability of cavitation nuclei, i.e., bubbles, to survive the off time between pulses. Due to the dependence of bubble dissolution on surface tension, surface-active agents may affect the stability of bubbles against dissolution. In this study, measurements of bubble dissolution rates in solutions of the surface-active polymer poly(propyl acrylic acid) (PPAA) were conducted to test this premise. The surface activity of PPAA varies with solution pH and concentration of dissolved polymer molecules. The surface tension of PPAA solutions (55-72 dynes/cm) that associated with the polymer surface activity was measured using the Wilhelmy plate technique. Samples of these polymer solutions then were exposed to 1.1 MHz high intensity focused ultrasound, and the dissolution of bubbles created by inertial cavitation was monitored using an active cavitation detection scheme. Analysis of the pulse echo data demonstrated that bubble dissolution time was inversely proportional to the surface tension of the solution. Finally, comparison of the experimental results with dissolution times computed from the Epstein-Plesset equation suggests that the radii of residual bubbles from inertial cavitation increase as the surface tension decreases.     

Minimizing the thermal losses from perfusion during focused ultrasound exposures with flowing microbubbles

This paper demonstrated the use of flowing microbubbles (MBs) to minimize thermal losses from perfusion during focused ultrasound exposures due to acoustic cavitation. Temperature and cavitation were simultaneously investigated as MBs flowing through a wall-less flow phantom with varying flow velocities (2-55 cm/s) and concentrations (0%-0.1%) when exposed at different acoustic power levels (5-120 W). The peak temperature at the end of ultrasonic exposures in the flow and in the outer of the vessel as well as the cavitation were higher than those pure controls measured at the same exposure parameters and flow velocities but without MBs. All the peak temperatures initially increased with increasing flow velocities of MBs, followed by a decrease of the peak temperatures with increasing flow velocities when the velocity was higher than the inflection velocity. Meanwhile, cavitation showed a trend of increases with increasing flow velocity. The inflection velocity and cavitation increased with increasing acoustic power and MBs concentration. Thermal lesion appeared around the vessel as MBs flow through the vessel, at which lesion was not observed originally without MBs. These results suggested that this may provide an effective way to minimize thermal losses from perfusion during focused ultrasound exposures.     

Compare ultrasound-mediated heating and cavitation between flowing polymer- and lipid-shelled microbubbles during focused ultrasound exposures

This paper compares the efficiency of flowing polymer- and lipid-shelled microbubbles (MBs) in the heating and cavitation during focused ultrasound exposures. Temperature and cavitation activity were simultaneously measured as the two types of shelled MBs and saline flowing through a 3 mm diameter vessel in the phantom with varying flow velocities (0-20 cm/s) at different acoustic power levels (0.6-20 W) with each exposure for 5 s. Temperature and cavitation for the lipid-shelled MBs were higher than those for the polymer-shelled MBs. Temperature rise decreased with increasing flow velocities for the two types of shelled MBs and saline at acoustic power 1.5 W. At acoustic power 11.1 W, temperature rise increased with increasing flow velocities for the lipid-shelled MBs. For the polymer-shelled MBs, the temperature rise increased with increasing flow velocities from 3-15 cm/s and decreased at 20 cm/s. Cavitation increased with increasing flow velocity for the two shelled MBs and there were no significant changes of cavitation with increasing flow velocities for saline. These results suggested that lipid-shelled MBs may have a greater efficiency than polymer-shelled MBs in heating and cavitation during focused ultrasound exposures.     

Efficient and controllable thermal ablation induced by short-pulsed HIFU sequence assisted with perfluorohexane nanodroplets

A HIFU sequence with extremely short pulse duration and high pulse repetition frequency can achieve thermal ablation at a low acoustic power using inertial cavitation. Because of its cavitation-dependent property, the therapeutic outcome is unreliable when the treatment zone lacks cavitation nuclei. To overcome this intrinsic limitation, we introduced perfluorocarbon nanodroplets as extra cavitation nuclei into short-pulsed HIFU-mediated thermal ablation. Two types of nanodroplets were used with perfluorohexane (PFH) as the core material coated with bovine serum albumin (BSA) or an anionic fluorosurfactant (FS) to demonstrate the feasibility of this study. The thermal ablation process was recorded by high-speed photography. The inertial cavitation activity during the ablation was revealed by sonoluminescence (SL). The high-speed photography results show that the thermal ablation volume increased by ∼643% and 596% with BSA-PFH and FS-PFH, respectively, than the short-pulsed HIFU alone at an acoustic power of 19.5 W. Using nanodroplets, much larger ablation volumes were created even at a much lower acoustic power. Meanwhile, the treatment time for ablating a desired volume significantly reduced in the presence of nanodroplets. Moreover, by adjusting the treatment time, lesion migration towards the HIFU transducer could also be avoided. The SL results show that the thermal lesion shape was significantly dependent on the inertial cavitation in this short-pulsed HIFU-mediated thermal ablation. The inertial cavitation activity became more predictable by using nanodroplets. Therefore, the introduction of PFH nanodroplets as extra cavitation nuclei made the short-pulsed HIFU thermal ablation more efficient by increasing the ablation volume and speed, and more controllable by reducing the acoustic power and preventing lesion migration.     

The mechanism of interaction between focused ultrasound and microbubbles in blood-brain barrier opening in mice

The activation of bubbles by an acoustic field has been shown to temporarily open the blood-brain barrier (BBB), but the trigger cause responsible for the physiological effects involved in the process of BBB opening remains unknown. Here, the trigger cause (i.e., physical mechanism) of the focused ultrasound-induced BBB opening with monodispersed microbubbles is identified. Sixty-seven mice were injected intravenously with bubbles of 1-2, 4-5, or 6-8 μm in diameter and the concentration of 10(7) numbers/ml. The right hippocampus of each mouse was then sonicated using focused ultrasound (1.5 MHz frequency, 100 cycles pulse length, 10 Hz pulse repetition frequency, 1 min duration). Peak-rarefactional pressures of 0.15, 0.30, 0.45, or 0.60 MPa were applied to identify the threshold of BBB opening and inertial cavitation (IC). Our results suggest that the BBB opens with nonlinear bubble oscillation when the bubble diameter is similar to the capillary diameter and with inertial cavitation when it is not. The bubble may thus have to be in contact with the capillary wall to induce BBB opening without IC. BBB opening was shown capable of being induced safely with nonlinear bubble oscillation at the pressure threshold and its volume was highly dependent on both the acoustic pressure and bubble diameter.