Research on behavior analysis of microbubbles for ultrasound contrast agent and optimum ultrasound diagnostic system

本研究的目的是建立超声造影剂微泡对超声暴露响应的实验分析系统，阐明微泡结构与微泡对超声暴露响应的关系，包括非线性响应。此外，我们旨在开发利用微泡非线性行为的超声诊断系统和优化超声造影剂微泡性能的超声诊断系统。在硬脂酸钠、棕榈酸钠和皂素的混合溶液中鼓泡并加入氯化钙制备表面活性剂包覆的手制微泡，通过实验与理论结果的拟合，得到其壳弹性参数S_p为0.3 N/m，壳摩擦参数S_f为0.07 μNs/m。考虑微泡包覆膜的影响和微泡周围液体可压缩性的影响，通过非线性微分方程发现，用于谐波成像的最佳微泡具有较小的壳弹性参数和较大的壳摩擦参数。利用装有Langevine型超声换能器的不锈钢振动盘从水箱底部形成水中驻波声场，并将微泡保持在水中驻波声场回路对应的位置，制作了微泡行为观察系统。实验结果表明，与市售微泡超声造影剂相比，我们制备的表面活性剂包覆微泡更适合于谐波成像。利用超声诊断设备b型图像亮度的变化来估计微泡的寿命。进一步发现，适用于该微泡谐波成像的超声暴露条件为：(1)超声暴露频率与微泡谐振频率重合；(2)超声暴露频率与微泡谐振频率的一半重合。提出并研制了用于谐波成像和次谐波成像的双峰型超声换能器，并在此基础上验证了试制超声换能器的可行性。具有双峰型频率特性的超声换能器可以有效地辐射基波分量，检测二次谐波或次谐波分量，是利用微泡非线性特性优化超声诊断系统的关键器件。少

The purposes of this research are the development of experimental and analyzing system of response of microbubble ultrasound contrast agents to ultrasound exposure and clarification of the relation between the structure of microbubbles and response of microbubbles against ultrasound exposure including nonlinear response. Furthermore, we aimed at the development of ultrasound diagnostic system using nonlinear behavior of microbubbles and ultrasound diagnostic system optimizing the performance of microbubbles for ultrasound contrast agents.For these purpose, it was found that the shell elasticity parameter S_p was 0.3 N/m and the shell friction parameter S_f was 0.07 μNs/m by curve fitting between experimental and theoretical results with numerical calculation for the hand made surfactant coated microbubbles manufactured by bubbling in the mixed solution of sodium stearate, sodium palmitate and saponine and adding calcium chloride.It was found by nonlinear differential equation consideri … More ng the effect of coating membrane of microbubbles and the effect of compressibility of the liquid surrounding microbubbles proposed by us that the optimum microbubble for harmonic imaging has the small shell elasticity parameter and large shell friction parameter.The microbubble behavior observation systems by forming standing wave acoustic field in water from the bottom of water tank with stainless vibrating disc equipped with the Langevine type ultrasound transducer and by holding microbubbles at the position corresponding to the loop of standing wave acoustic field in water were manufactured.We can mention by these results that our hand made surfactant coated microbubbles were appropriate to harmonic imaging comparing with commercial microbubble ultrasound contrast agents.The life time of this microbubble was estimated with the change of brightness in the B-mode image of ultrasound diagnostic equipment. Furthermore, it was found that the ultrasound exposure condition appropriate to harmonic imaging with this microbubble were (1) to coincide between the ultrasound exposure frequency and the resonant frequency of microbubble and (2) to coincide between the ultrasound exposure frequency and the half of resonant frequency of microbubble.The ultrasound transducers with double peak type frequency characteristics for harmonic imaging and those for subharmonic imaging were proposed and developed and the availability of these trially manufactured ultrasound transducers were confirmed on the basis of these results. As the fundamental ultrasound component can be radiated and the second harmonic component or subharmonic component can be detected effectively by these ultrasound transducers with double peak type frequency characteristics, these ultrasound transducers can be thought as the key device for optimum ultrasound diagnostic system using nonlinear behavior of microbubbles. Less