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CN109085247B - Ultrasonic contrast agent cavitation bubble group resonance state measurement method - Google Patents

Ultrasonic contrast agent cavitation bubble group resonance state measurement method Download PDF

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CN109085247B
CN109085247B CN201810676330.0A CN201810676330A CN109085247B CN 109085247 B CN109085247 B CN 109085247B CN 201810676330 A CN201810676330 A CN 201810676330A CN 109085247 B CN109085247 B CN 109085247B
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兰庆
王月兵
曹永刚
叶晓同
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China Jiliang University
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Abstract

本发明涉及一种超声造影剂空化泡群共振状态测量方法。本发明是在水介质中加入超声造影剂后,首先用高频换能器激励泡群,泡群会因为受到声场的作用产生稳态空化,从而导致测量声波幅值发生变化(从示波器上可观察波形的振动情况),然后用低频换能器激励泡群达到共振状态,此时的声波幅值会发生明显变化(信号剧烈的抖动),所以可通过测量声波幅值变化得到泡群是否达到共振状态。本发明将有助于通过准确的监测超声造影剂泡群的共振状态,在焦域中产生超声治疗所需要的高声压,减少高强度聚焦声波在含微气泡液体中传播时的衰减和色散,这对超声医疗诊断、治疗和实验测量方面有着非常重要的意义。

Figure 201810676330

The invention relates to a method for measuring the resonance state of a cavitation bubble group of an ultrasonic contrast agent. In the present invention, after adding the ultrasonic contrast agent into the aqueous medium, first use a high-frequency transducer to excite the bubble group, and the bubble group will generate steady-state cavitation due to the action of the sound field, thus resulting in the change of the measured sound wave amplitude (from the oscilloscope on the oscilloscope). The vibration of the waveform can be observed), and then use the low-frequency transducer to excite the bubble group to reach the resonance state. At this time, the amplitude of the sound wave will change significantly (the signal shakes violently), so it can be measured by measuring the change in the sound wave amplitude. reach a resonance state. The invention will help to generate the high sound pressure required for ultrasonic treatment in the focal region by accurately monitoring the resonance state of the ultrasonic contrast agent bubble group, and reduce the attenuation and dispersion of the high-intensity focused sound wave when it propagates in the liquid containing microbubbles , which is of great significance to ultrasound medical diagnosis, treatment and experimental measurement.

Figure 201810676330

Description

一种超声造影剂空化泡群共振状态测量方法A kind of ultrasonic contrast agent cavitation bubble group resonance state measurement method

技术领域technical field

本发明属于超声空化和声学技术领域的结合,具体涉及一种超声造影剂空化泡群共振状态测量方法。The invention belongs to the combination of ultrasonic cavitation and acoustic technology, and particularly relates to a method for measuring the resonance state of ultrasonic contrast agent cavitation bubble groups.

背景技术Background technique

近年来在临床医学超声诊断与生物组织成像领域中,微泡型超声造影剂受到越来越多的关注,超声技术也被应用到多种治疗设备中,国内外大量的研究成果表明,利用声波激励微气泡时所产生的非线性振动和稳态空化,可以提高超声治疗的效率、实施血管内溶栓治疗,而通过微纳气泡携带治疗药物或基因,使用超声作为介导手段,能够进行抗肿瘤药物靶向递送、基因定位转染或递送等方面的治疗,因此,将微气泡和超声结合起来进行一些重大疾病的治疗已成为国内外医学界所关注的热点之一。In recent years, in the field of clinical medical ultrasound diagnosis and biological tissue imaging, microbubble ultrasound contrast agents have received more and more attention, and ultrasound technology has also been applied to a variety of therapeutic equipment. The nonlinear vibration and steady-state cavitation generated when microbubbles are excited can improve the efficiency of ultrasound therapy and implement intravascular thrombolysis. The micro-nanobubbles carry therapeutic drugs or genes, and ultrasound is used as a mediation method to carry out treatment. Therefore, the combination of microbubble and ultrasound for the treatment of some major diseases has become one of the hot spots of domestic and foreign medical circles.

当液体介质中含有大量气泡时,入射声波与微气泡振动是一个相互影响的过程,微气泡的存在改变了介质的物理特性,增加了介质的散射、吸收和非线性系数,同时在焦域附近,泡群共振对焦域中声压分布将产生较大影响,会导致泡群中微气泡产生剧烈的非线性振动及空化。为了减少高强度聚焦声波在含气泡液体中传播时的衰减和色散,通过高频聚焦脉冲在焦域中形成稳态空化泡群,进而使用低频聚焦超声激发泡群共振,在焦点处可以形成粉碎结石所需要的高声压。为研究激发泡群共振时所需要的声场条件,分析在共振状态下泡群内部声压分布和微气泡振动规律,获得共振条件下泡群内部声压分布规律及与激励声压幅度、频率之间的关系,所获得的焦域声压分布会影响对治疗机理和治疗效果的判断。所以寻求一种空化泡群共振状态测量方法显得尤为重要。When the liquid medium contains a large number of bubbles, the incident sound wave and the vibration of microbubbles are a process of mutual influence. The existence of microbubbles changes the physical properties of the medium and increases the scattering, absorption and nonlinear coefficients of the medium. , the sound pressure distribution in the focal region of the bubble group resonance will have a greater impact, which will lead to the violent nonlinear vibration and cavitation of the microbubbles in the bubble group. In order to reduce the attenuation and dispersion of high-intensity focused acoustic waves propagating in bubble-containing liquids, high-frequency focused pulses are used to form steady-state cavitation bubbles in the focal region, and then low-frequency focused ultrasound is used to excite the bubble group resonance, which can form at the focal point. High sound pressure required to break up stones. In order to study the sound field conditions required for the excitation of the bubble group resonance, the internal sound pressure distribution of the bubble group and the vibration law of the micro-bubble were analyzed under the resonance state, and the internal sound pressure distribution law of the bubble group under the resonance condition and the relationship between the excitation sound pressure amplitude and frequency were obtained. The obtained sound pressure distribution in the focal region will affect the judgment of the treatment mechanism and treatment effect. Therefore, it is very important to seek a method for measuring the resonance state of cavitation bubble groups.

发明内容SUMMARY OF THE INVENTION

本发明针对现有技术的不足,提供了一种超声造影剂空化泡群共振状态测量方法。Aiming at the deficiencies of the prior art, the present invention provides a method for measuring the resonance state of the cavitation bubble group of an ultrasonic contrast agent.

本发明的技术解决方案为:The technical solution of the present invention is:

测量泡群共振状态时需要确定达到气泡空化的条件和共振频率的大小,而超声波能否产生空化现象和空化阈值有很大关系,对于分布函数为f(R0)的气泡群而言,泡群的出现会对入射声波产生强烈的散射和阻挡作用,由于大量气泡和驱动声场的相互作用,泡群中气泡的振动明显区别于单个气泡的情况,气泡粒径变化也存在不同的状况,其声波幅值不能简单地视为是单个气泡的线性叠加,所有粒径大小气泡形成的声波幅值总和为:When measuring the resonance state of the bubble group, it is necessary to determine the conditions for reaching the bubble cavitation and the size of the resonance frequency, and whether the ultrasonic wave can produce cavitation has a great relationship with the cavitation threshold. For the bubble group whose distribution function is f(R 0 ), the In other words, the appearance of the bubble group will have a strong scattering and blocking effect on the incident sound wave. Due to the interaction between a large number of bubbles and the driving sound field, the vibration of the bubble in the bubble group is obviously different from that of a single bubble, and the change of the bubble size is also different. In this case, the acoustic wave amplitude cannot simply be regarded as a linear superposition of individual bubbles. The sum of the acoustic wave amplitudes formed by bubbles of all particle sizes is:

Figure BDA0001709898130000021
Figure BDA0001709898130000021

其中,P0为标准静压力,Pa为入射波声压幅值,圆频率ω=2πf,f为入射波频率,α'为加入到水介质中超声造影剂的衰减系数,计算方法为:Among them, P 0 is the standard static pressure, P a is the amplitude of the sound pressure of the incident wave, the circular frequency ω=2πf, f is the frequency of the incident wave, and α' is the attenuation coefficient of the ultrasonic contrast agent added to the aqueous medium. The calculation method is:

Figure BDA0001709898130000022
Figure BDA0001709898130000022

其中,x表示发射信号和接收信号之间的距离;p和px分别表示水和含超声造影剂介质中接收信号幅值;α为已知超声使用频率和温度下纯净液体的衰减系数。R为气泡粒径大小,其随时间t和初始粒径R0的变化关系式为:Among them, x represents the distance between the transmitted signal and the received signal; p and p x represent the amplitude of the received signal in water and medium containing ultrasound contrast agent, respectively; α is the attenuation coefficient of pure liquid at the known ultrasonic frequency and temperature. R is the size of the bubble particle size, and its relationship with time t and the initial particle size R 0 is:

Figure BDA0001709898130000031
Figure BDA0001709898130000031

T表示超声造影剂的平均消除半衰期,ψ(R0,t)表示体积分数随气泡初始粒径R0和时间t变化的函数,其表达式为:T represents the average elimination half-life of the ultrasound contrast agent, ψ(R 0 ,t) represents the function of the volume fraction with the initial bubble size R 0 and time t, and its expression is:

Figure BDA0001709898130000032
Figure BDA0001709898130000032

f(R0)表示气泡个数分布受粒径大小影响的函数,其表达式为:f(R 0 ) represents the function of the number distribution of bubbles affected by the particle size, and its expression is:

Figure BDA0001709898130000033
Figure BDA0001709898130000033

k为波数,根据气泡群的散射特性,得到泡群的波数表达式为:k is the wave number. According to the scattering characteristics of the bubble group, the wave number expression of the bubble group is obtained as:

Figure BDA0001709898130000034
Figure BDA0001709898130000034

其中,阻尼系数δ=2πR(R0,t)/λ=2πfR(R0,t)/c,N为气泡的个数,在实验所选区域不太大的情况下,气泡的个数N和体积分数ψ的关系近似满足:Among them, the damping coefficient δ=2πR(R 0 ,t)/λ=2πfR(R 0 ,t)/c, N is the number of bubbles, and the number of bubbles N is when the area selected for the experiment is not too large The relationship with the volume fraction ψ approximately satisfies:

Figure BDA0001709898130000035
Figure BDA0001709898130000035

并且满足

Figure BDA0001709898130000036
f0为气泡的谐振频率,根据气泡动力学得到含气微泡的谐振频率是由气体、液体以及泡膜的性质共同决定的,可表示为:and satisfy
Figure BDA0001709898130000036
f 0 is the resonant frequency of the bubble. According to the bubble dynamics, the resonant frequency of the gas-containing microbubble is determined by the properties of the gas, liquid and bubble film, and can be expressed as:

Figure BDA0001709898130000041
Figure BDA0001709898130000041

其中,微泡内气体多方指数γ=1.07,液体密度ρ=998kg·m-3,液体中静压P0=1.013×105Pa,液体表面张力系数σ=0.076N·m-1,泡膜的弹力系数Sp=4.2N·m-1Among them, the gas polytropic index γ=1.07 in the microbubble, the liquid density ρ=998kg·m -3 , the static pressure in the liquid P 0 =1.013×10 5 Pa, the liquid surface tension coefficient σ=0.076N·m -1 , the bubble film The elastic coefficient Sp = 4.2N·m -1 .

根据实验测量需求(高低频换能器一起工作),得到气泡群达到共振状态时的声波幅值表达式为:According to the experimental measurement requirements (high and low frequency transducers work together), the expression of the acoustic wave amplitude when the bubble group reaches the resonance state is:

Figure BDA0001709898130000042
Figure BDA0001709898130000042

其中,Pa1为加在高频换能器上的入射声波幅值,ω1=2πf1,f1为入射波高频频率,Pa2为加在低频换能器上的入射声波幅值,ω2=2πf2,f为入射波低频频率。通过高频聚焦脉冲信号在焦域中形成稳态空化泡群,然后使用低频聚焦超声激发泡群发生共振,在焦点处形成高声压,通过程控计算机中的LABVIEW程序可实时显示焦域的声波幅值变化,从而可判断泡群是否达到共振状态。Among them, P a1 is the amplitude of the incident sound wave applied to the high-frequency transducer, ω 1 =2πf 1 , f 1 is the high-frequency frequency of the incident wave, P a2 is the amplitude of the incident sound wave applied to the low-frequency transducer, ω 2 =2πf 2 , where f is the low frequency frequency of the incident wave. A steady-state cavitation bubble group is formed in the focal area through a high-frequency focusing pulse signal, and then the bubble group is excited to resonate with low-frequency focused ultrasound, forming a high sound pressure at the focal point. The LABVIEW program in the computer can display the focal area in real time The amplitude of the sound wave changes, so that it can be judged whether the bubble group has reached the resonance state.

本发明中的实验装置包括信号发生器、功率放大器、聚焦换能器、高精度三维超声扫描控制机构、探针水听器、数字示波器、程控计算机等。其中,两个聚焦换能器固定在水槽相连的两侧,避免了同时移动换能器和水听器时,导致三者的声轴达不到共声轴的状态,水听器安装在高精度三维超声扫描控制机构上,由程控计算机控制水听器运动,采集不同位置的信号,水听器作为声波接收端与数字示波器相连,两个换能器分别连着两个功率放大器,再连着两个信号发生器,信号发生器的触发信号作为同步信号接入到数字示波器,数字示波器与程控计算机相连,对信号进行读取和存储。The experimental device in the present invention includes a signal generator, a power amplifier, a focusing transducer, a high-precision three-dimensional ultrasonic scanning control mechanism, a probe hydrophone, a digital oscilloscope, a program-controlled computer, and the like. Among them, the two focusing transducers are fixed on both sides of the water tank, which avoids that when the transducer and the hydrophone are moved at the same time, the sound axis of the three cannot reach the state of the common sound axis, and the hydrophone is installed in a high On the precision three-dimensional ultrasonic scanning control mechanism, the motion of the hydrophone is controlled by the program-controlled computer, and the signals at different positions are collected. The hydrophone is connected to the digital oscilloscope as the sound wave receiving end. With two signal generators, the trigger signal of the signal generator is connected to the digital oscilloscope as a synchronization signal, and the digital oscilloscope is connected with the program-controlled computer to read and store the signals.

进一步说,所述的两个信号发生器采用的是具备可以同时发送双通道信号功能的普源精电DG4062信号发生器,并可实现同相位操作的信号发生器。Furthermore, the two signal generators used are the DG4062 signal generators of Puyuan Jingdian which can send dual-channel signals at the same time, and the signal generators that can realize the same phase operation.

进一步说,所述的换能器采用的一个是直径为900mm,谐振频率为990kHz,聚焦距离为105mm的球壳型换能器,另一个是直径为500mm,谐振频率为100kHz,聚焦距离为50mm的聚焦换能器,两个换能器固定在水槽相连的两端,二者的焦域相对着,避免了同时移动换能器和水听器时,导致三者达不到共声轴的状态。Further, one of the transducers used is a spherical shell type transducer with a diameter of 900mm, a resonant frequency of 990kHz, and a focusing distance of 105mm, and the other is a spherical transducer with a diameter of 500mm, a resonance frequency of 100kHz, and a focusing distance of 50mm. The focusing transducer, the two transducers are fixed at the two ends of the water tank, and the focal areas of the two are opposite to each other, avoiding the simultaneous movement of the transducer and the hydrophone, which will cause the three to fail to reach the common sound axis. state.

进一步说,所述的水听器采用的是探针水听器,满足实验需求。Further, the hydrophone is a probe hydrophone, which meets the experimental requirements.

进一步说,所述的放大器是采用的一个是国产的JYH-200中频功率放大器,可放大频率低于400kHz的换能器;一个是进口的RPR-400功率放大器,最高功率输出达8KW,满足实验需求。Further, the amplifiers mentioned are a domestic JYH-200 intermediate frequency power amplifier, which can amplify transducers with a frequency lower than 400kHz; the other is an imported RPR-400 power amplifier, with a maximum power output of 8KW, which meets the experimental requirements. need.

进一步说,所述的示波器采用的是普源精电的DS2102双通道示波器,它具备波形触发、内存读取、存储功能,实时采样率最高达2GSa/s,带宽达到200MHz,并具有串口通信,可直接与程控计算机相连,可同时接收两个换能器发射的信号。Further, the oscilloscope used is the DS2102 dual-channel oscilloscope of Puyuan Jingdian, which has the functions of waveform triggering, memory reading and storage, the real-time sampling rate is up to 2GSa/s, the bandwidth is up to 200MHz, and it has serial communication. It can be directly connected with the program-controlled computer, and can receive the signals emitted by two transducers at the same time.

进一步说,所述的高精度三维超声扫描控制机构,其系统最小的有效控制步进精度为0.02mm,可实现水下三维运动,并可准确实现水下定位。Furthermore, the high-precision three-dimensional ultrasonic scanning control mechanism has a minimum effective control step accuracy of 0.02mm, which can realize underwater three-dimensional motion and accurately realize underwater positioning.

本发明的有益效果:综上所述,本发明的测量方法,可以针对不同种类的超声造影剂进行测量;水槽的尺寸设计为20cm×20cm×40cm,即保证了探针水听器可以在水槽内进行三维运动,以便找到泡群空化焦域,也保证了超声造影剂的浓度不至于太低,减小微泡向实验区域外扩散,使得微泡在实验测量区域内充分发挥作用,避免了超声造影剂的浪费;水槽上固定的两个高低频换能器即可以单独工作也可以同时工作,单独工作时可以达到稳态空化的状态,同时工作时可以更好的找到气泡群共振的状态,避免了单个换能器激励时的高功率,大大的减小了信号发生器的输入,使得很小的信号激励就能达到共振的状态,实验测量方法可以准确、实时的找到空化泡群共振的状态且操作简便、快捷。该测量方法的提出,将有助于通过使用适当的激励就能准确的监测超声造影剂泡群的共振状态,在焦域中产生超声治疗所需要的高声压,减少高强度聚焦声波在含微气泡液体中传播时的衰减和色散,这对超声医疗诊断、治疗和实验测量方面有着非常重要的意义。Beneficial effects of the present invention: In summary, the measurement method of the present invention can measure different types of ultrasonic contrast agents; the size of the water tank is designed to be 20cm×20cm×40cm, which ensures that the probe hydrophone can be placed in the water tank. Three-dimensional movement is carried out in order to find the cavitation focal area of the bubble group, which also ensures that the concentration of the ultrasound contrast agent is not too low, reduces the diffusion of microbubbles to the outside of the experimental area, and makes the microbubbles fully function in the experimental measurement area. It eliminates the waste of ultrasound contrast agent; the two high and low frequency transducers fixed on the water tank can work alone or at the same time. When working alone, a steady state of cavitation can be achieved, and at the same time, the bubble group resonance can be better found when working. It avoids the high power when a single transducer is excited, and greatly reduces the input of the signal generator, so that a very small signal excitation can reach the state of resonance. The experimental measurement method can accurately and real-time find cavitation. The state of bubble group resonance is easy and fast to operate. The proposed measurement method will help to accurately monitor the resonance state of the ultrasound contrast agent bubble group by using appropriate excitation, generate the high sound pressure required for ultrasound therapy in the focal region, and reduce the high-intensity focused sound wave in the containing Attenuation and dispersion during propagation in microbubble liquids are of great significance to ultrasonic medical diagnosis, treatment and experimental measurements.

附图说明Description of drawings

图1本发明测量装置示意图。Fig. 1 is a schematic diagram of the measuring device of the present invention.

图2输出脉冲信号暂态稳态示意图。Figure 2 is a schematic diagram of the transient steady state of the output pulse signal.

图中:1、数字示波器,2、水槽,3、程控计算机,4、高精度三维超声扫描控制机构,5、探针水听器,6、聚焦换能器b,7、信号发生器a,8、功率放大器a,9、聚焦换能器a,10、信号发生器b,11、功率放大器b。In the picture: 1. Digital oscilloscope, 2. Water tank, 3. Program-controlled computer, 4. High-precision three-dimensional ultrasonic scanning control mechanism, 5. Probe hydrophone, 6. Focusing transducer b, 7. Signal generator a, 8. Power amplifier a, 9, focusing transducer a, 10, signal generator b, 11, power amplifier b.

具体实施方式Detailed ways

下面结合附图对本发明作进一步的说明:Below in conjunction with accompanying drawing, the present invention is further described:

本发明的测量原理:在水介质中加入超声造影剂后,首先用高频换能器激励泡群,泡群会因为受到声场的作用产生稳态空化,从而导致测量声波幅值发生变化(从示波器上可观察波形的振动情况),然后用低频换能器激励泡群达到共振状态,此时的声波幅值会发生明显变化(信号剧烈的抖动),所以可通过测量声波幅值变化得到泡群是否达到共振状态。The measurement principle of the present invention: after adding the ultrasonic contrast agent to the aqueous medium, first use a high-frequency transducer to excite the bubble group, and the bubble group will generate steady-state cavitation due to the action of the sound field, thereby causing the measured sound wave amplitude to change ( The vibration of the waveform can be observed from the oscilloscope), and then the low-frequency transducer is used to excite the bubble group to reach the resonance state. At this time, the amplitude of the sound wave will change significantly (the signal shakes violently), so it can be obtained by measuring the change of the sound wave amplitude. Whether the bubble group reaches the resonance state.

如图1所示,首先在水槽2中加入经溶氧脱氧处理过的除气水,然后将配置好的超声造影剂混悬液(SonoVue)加入到水介质中。信号发生器7产生的猝发正弦脉冲信号作为同步信号接入数字示波器1的外部触发,用于捕获声压波形和计算聚焦换能器9和探针水听器5之间的距离,同时利用信号发生器1产生的30个周期、中心频率为990kHz的连续信号通过功率放大器8(频率范围0.5MHz~45MHz,增益50dB)激励聚焦换能器9(中心频率为990kHz,直径为900mm)发射声波,在水槽中形成辐射声场,探针水听器5作为接收器件将接收到声信号转化为电信号,在数字示波器1上进行显示。探针水听器5安装在高精度三维超声扫描控制机构4上,由程控计算机3控制探针水听器5运动,寻找声场空化焦域(尽量保证换能器和水听器共声轴,以增加系统的接收灵敏度,提高对微弱信号的接收能力),然后设置参数观察数字示波器1上的信号变化情况,在声波达到稳态空化后,再用信号发生器10通过功率放大器11激励聚焦换能器6发射信号,观察空化泡群的共振情况,然后将两个信号发生器的信号作同相位处理,在数字示波器上得到空化焦域的声波信号,并通过程控计算机3中的LABVIEW程序串口对数字示波器1上的信号进行读取和存储,得到空化焦域的声波数值,通过对信号的处理,得到不同情况下的空化泡群的共振状态特性。As shown in FIG. 1 , firstly, degassed water treated with dissolved oxygen and deoxygenation was added to the water tank 2 , and then the prepared ultrasonic contrast agent suspension (SonoVue) was added to the aqueous medium. The burst sinusoidal pulse signal generated by the signal generator 7 is connected to the external trigger of the digital oscilloscope 1 as a synchronization signal, which is used to capture the sound pressure waveform and calculate the distance between the focusing transducer 9 and the probe hydrophone 5, and at the same time use the signal The 30-cycle continuous signal with the center frequency of 990kHz generated by the generator 1 excites the focusing transducer 9 (the center frequency is 990kHz, the diameter is 900mm) through the power amplifier 8 (frequency range 0.5MHz~45MHz, gain 50dB) to emit sound waves, A radiation sound field is formed in the water tank, and the probe hydrophone 5 is used as a receiving device to convert the received sound signal into an electrical signal, which is displayed on the digital oscilloscope 1 . The probe hydrophone 5 is installed on the high-precision three-dimensional ultrasonic scanning control mechanism 4, and the movement of the probe hydrophone 5 is controlled by the program-controlled computer 3 to find the cavitation focal area of the sound field (try to ensure that the transducer and the hydrophone share the same sound axis. , in order to increase the receiving sensitivity of the system and improve the ability to receive weak signals), and then set the parameters to observe the signal changes on the digital oscilloscope 1. After the sound wave reaches steady-state cavitation, the signal generator 10 is used to stimulate the power amplifier 11. The focusing transducer 6 transmits a signal, observes the resonance of the cavitation bubble group, and then processes the signals of the two signal generators in the same phase, and obtains the acoustic wave signal in the cavitation focal domain on the digital oscilloscope, and transmits it through the process control computer 3. The serial port of the LABVIEW program reads and stores the signal on the digital oscilloscope 1, and obtains the acoustic wave value of the cavitation focal region. Through the processing of the signal, the resonance state characteristics of the cavitation bubble group under different conditions are obtained.

(1)信号激励部分(1) Signal excitation part

由于实验过程中需要为示波器提供与发射信号同步的触发信号,用于捕获声压波形和计算发射波和接收波之间的时延,故选用的信号发生器为普源精电的DG4062双通道信号发生器,它具备双通道可以同时发送信号的功能,满足实验的要求。但是信号发生器的激励电压幅度有限,不足以激励换能器产生空化现象,因此需要对其进行放大。实验选用国产的JYH-200中频功率放大器,对低频换能器器进行激励;还选用RITEC的RPR-4000信号的功率放大器对高频换能器进行激励,它具有自发自收、门限激励、漏电保护等功能,最高功率输出达8KW,满足实验要求。同时为了达到空化气泡共振状态,使用两个型号一样的信号发生器(进行同相位操作)通过放大进行激励换能器。发射信号时为了保护换能器的同时避免产生混响场,激励信号一般采用猝发正弦脉冲信号,它既有脉冲信号性质又有稳定状态,可以在反射信号到来之前完成数据采集,避免形成混响场。Since it is necessary to provide the oscilloscope with a trigger signal synchronized with the transmitted signal during the experiment, it is used to capture the sound pressure waveform and calculate the time delay between the transmitted wave and the received wave, so the selected signal generator is the DG4062 dual-channel from Puyuan Jingdian. Signal generator, it has the function of two channels that can send signals at the same time to meet the requirements of the experiment. However, the excitation voltage amplitude of the signal generator is limited, which is not enough to excite the transducer to produce cavitation, so it needs to be amplified. In the experiment, the domestic JYH-200 intermediate frequency power amplifier was used to excite the low-frequency transducer; the RPR-4000 signal power amplifier of RITEC was also used to excite the high-frequency transducer. Protection and other functions, the maximum power output is up to 8KW, which meets the experimental requirements. At the same time, in order to achieve the cavitation bubble resonance state, two signal generators of the same model (operating in the same phase) are used to excite the transducer through amplification. In order to protect the transducer and avoid the reverberation field when transmitting the signal, the excitation signal generally adopts a burst sinusoidal pulse signal, which has both pulse signal properties and a stable state, and can complete data acquisition before the arrival of the reflected signal to avoid the formation of reverberation. field.

(2)数据采集部分(2) Data collection part

数据采集部分包括数字示波器和程控计算机两个部分。数字示波器选用的是普源精电的DS2102双通道示波器,它具备波形触发、内存读取、存储功能,实时采样率最高达2GSa/s,带宽达到200MHz,并具有串口通信,可通过软件编程来实现示波器的参数设置、状态查询和读取数据等,满足实验需求,数字示波器作为中转部件将探针水听器接收的信号传输给程控计算机,在计算机上进行显示和存储。The data acquisition part includes two parts: digital oscilloscope and program-controlled computer. The digital oscilloscope selected is the DS2102 dual-channel oscilloscope of Puyuan Jingdian, which has waveform triggering, memory reading and storage functions, real-time sampling rate up to 2GSa/s, bandwidth up to 200MHz, and serial communication, which can be programmed by software. Realize the parameter setting of the oscilloscope, status query and read data, etc., to meet the experimental needs.

当正弦脉冲激励换能器时,换能器被驱动,开始阶段需要一段时间才能达到稳定的工作状态,当激励信号结束后,换能器还需要进行一段时间的阻尼振动。因此输出的脉冲信号的前部和尾部会有暂态现象出现,如图2所示。诸如有效声压、声工作频率等参数都是按换能器稳态工作状态时定义的,因此信号的暂态部分不可用且激励脉冲的宽度不能小于暂态过程,根据实际情况,实验给了30个周期信号,采集信号时读取稳态部分的周期信号(减小信号的不稳定性),然后通过对波形的处理得到声波幅值,进而可分析出空化泡群共振状态特性。When the sinusoidal pulse excites the transducer, the transducer is driven, and it takes a period of time to reach a stable working state in the initial stage. After the excitation signal ends, the transducer needs to damp vibration for a period of time. Therefore, there will be transient phenomena at the front and the tail of the output pulse signal, as shown in Figure 2. Parameters such as effective sound pressure and sound operating frequency are defined according to the steady state of the transducer, so the transient part of the signal is unavailable and the width of the excitation pulse cannot be smaller than the transient process. According to the actual situation, the experiment gives 30 periodic signals, read the periodic signal of the steady state part when collecting the signal (reduce the instability of the signal), and then obtain the acoustic wave amplitude by processing the waveform, and then analyze the resonance state characteristics of the cavitation bubble group.

(3)运动控制部分(3) Motion control part

实验中的运动控制部分主要是由计算机里面的LABVIEW程序控制着高精度三维扫描运动控制机构里的步进电机运动,步进电机作为运动的执行机构,接收计算机通过发送的脉冲信号,并将接收的电脉冲转换为自身的角位移,从而带动探针水听器在水槽中进行三维运动,完成各处信号的采集。The motion control part in the experiment is mainly controlled by the LABVIEW program in the computer to control the motion of the stepping motor in the high-precision three-dimensional scanning motion control mechanism. The electric pulse of the probe is converted into its own angular displacement, thereby driving the probe hydrophone to perform three-dimensional movement in the water tank to complete the acquisition of signals everywhere.

综上所述,本发明的测量方法,适合对不同种类的超声造影剂进行测量;水槽上的两个高低频换能器即可以单独工作也可以同时工作,从而更好的达到泡群稳态空化和空化泡群共振状态;水槽的尺寸设计即保证了探针水听器可以在水槽内进行三维运动,以便找到泡群空化焦域,也保证了超声造影剂的浓度不至于太低,减小微泡向实验区域外进行扩散,使得微泡在实验测量区域内充分发挥作用,避免了超声造影剂的浪费。该测量方法的提出,将有助于通过准确的监测超声造影剂泡群的共振状态,在焦域中产生超声治疗所需要的高声压,减少高强度聚焦声波在含微气泡液体中传播时的衰减和色散,这对超声医疗诊断、治疗和实验测量方面有着非常重要的意义。To sum up, the measurement method of the present invention is suitable for measuring different types of ultrasound contrast agents; the two high and low frequency transducers on the water tank can work independently or simultaneously, so as to better achieve the steady state of the bubble group Cavitation and cavitation bubble group resonance state; the size design of the water tank ensures that the probe hydrophone can move in three dimensions in the water tank to find the cavitation focal region of the bubble group, and also ensures that the concentration of the ultrasound contrast agent will not be too high. Low, reducing the diffusion of microbubbles to the outside of the experimental area, so that the microbubbles can fully function in the experimental measurement area, avoiding the waste of ultrasonic contrast agents. The proposed measurement method will help to accurately monitor the resonance state of the ultrasonic contrast agent bubble group, generate the high sound pressure required for ultrasonic treatment in the focal region, and reduce the propagation of high-intensity focused sound waves in the liquid containing microbubbles. Attenuation and dispersion, which are of great significance to ultrasonic medical diagnosis, treatment and experimental measurement.

Claims (1)

1. A resonance state measurement method for cavitation bubble groups of an ultrasonic contrast agent is characterized by comprising the following steps:
when the resonance state of the bubble group is measured, the condition for achieving bubble cavitation and the resonance frequency are determined, and the distribution function is f (R)0) The occurrence of the bubble group can generate strong scattering and blocking effects on incident sound waves, the vibration of the bubbles in the bubble group is obviously different from the situation of a single bubble due to the interaction of a large number of bubbles and a driving sound field, the change of the bubble particle size also has different conditions, the amplitude of the sound wave cannot be simply regarded as the linear superposition of the single bubble, and the sum of the amplitudes of the sound waves formed by the bubbles with all particle sizes is:
Figure FDA0002654820890000011
wherein, P0Is a standard static pressure, PaThe acoustic pressure amplitude of the incident wave is represented by the circular frequency omega which is 2 pi f, f is the frequency of the incident wave, and a' is the attenuation coefficient of the ultrasonic contrast agent added into the aqueous medium:
Figure FDA0002654820890000012
wherein x represents the distance between the transmitted signal and the received signal; p is a radical of0And pxRespectively representing the amplitude of a received signal in water and a medium containing an ultrasonic contrast agent; a is the attenuation coefficient of pure liquid under the known ultrasonic use frequency and temperature; r is the bubble size over time t and the primary particle size R0The variation relation of (A) is as follows:
Figure FDA0002654820890000013
t represents the mean elimination half-life of the ultrasound contrast agent, # R0And t) represents the volume fraction as a function of the bubble primary particle diameter R0And the time t, expressed as:
Figure FDA0002654820890000014
f(R0) The distribution function of the number distribution of the bubbles influenced by the size of the particle diameter is expressed as follows:
Figure FDA0002654820890000021
k is wave number, and the expression of the wave number of the bubble group is obtained according to the scattering characteristics of the bubble group as follows:
Figure FDA0002654820890000022
wherein the damping coefficient is 2 pi R (R)0,t)/λ=2πfR(R0And t)/c, N is the number of the bubbles, and the relation between the number N of the bubbles and the volume fraction psi approximately satisfies the following conditions:
Figure FDA0002654820890000023
and satisfy
Figure FDA0002654820890000024
f0The resonance frequency of the gas-containing microbubbles, which is obtained from the dynamics of the bubbles, is determined by the properties of the gas, the liquid and the bubble membrane, and is expressed as:
Figure FDA0002654820890000025
wherein the gas polytropic index gamma in the microbubble is 1.07, and the liquid density rho is 998 kg.m-3Hydrostatic pressure P in the liquid0=1.013×105Pa, liquidSurface tension coefficient sigma 0.076 N.m-1Coefficient of elasticity S of bubble filmp=4.2N·m-1
Thereby obtaining the acoustic wave amplitude expression when the bubble group reaches the resonance state as follows:
Figure FDA0002654820890000026
wherein, Pa1For the amplitude, omega, of the incident sound wave applied to the high-frequency transducer1=2πf1,f1For high frequency of incident wave, Pa2For the amplitude, omega, of the incident sound wave applied to the low-frequency transducer2=2πf2,f2Is the incident wave low frequency; a stable cavitation bubble group is formed in a focal region through a high-frequency focusing pulse signal, then the bubble group is excited to resonate by using low-frequency focusing ultrasonic waves, high sound pressure is formed at the focal point, and the change of the sound wave amplitude of the focal region is displayed in real time through an LABVIEW program in a process control computer, so that whether the bubble group reaches a resonance state or not can be judged.
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