双频控制组织中纳米液滴相变微泡、成核阈值与区域及高效精细治疗

Due to the nanoscale size, phase-shift nanodroplet can preferentially accumulate in tissue interstitial space and aid to increase the efficiency in the cavitation-enhanced ultrasound therapy such as tumor thermal ablation. Nevertheless, investigation on the nanodroplet phase-shift mechanism is mainly limited within liquid medium. To clarify the phase-shift mechanism and characterize the phase-shifted microbubbles in tissue so as to further exert the advantage as tissue cavitation nuclei, this project propose to investigate and develop a dual frequency technique to control the nanodroplet phase-shift process, including the size distribution of phase-shifted microbubbles, the nucleation threshold and region, achieving the efficient and precise tumor thermal ablation. This project concentrates on (1) Dissolution kinetics of multi-component gas bubble in tissue and an acoustically original size distribution estimation method for multi-component gas bubbles; (2) Control the nucleation threshold, region and bubble size distribution for phase-shifted microbubbles through regulating the matching ratio between the intensities of dual-frequency focused ultrasound for annual array transducer;(3)Apply the regulation technique proposed above into the tumor thermal ablation, demonstrating the efficiency and precision through the experiments in optic-transparent tissue-mimicking phantom and further the tumor model experiments in vivo. This project present a potential to put the acoustic droplet vaporization mechanism, the characterization of phase-shifted microbubbles and the control of phase shift process toward a new height.

纳米相变液滴因其尺寸小易于进入组织间隙等优势，能够有效提高肿瘤热消融等基于空化效应的超声治疗效率，然而目前纳米相变液滴的机制研究多局限于液体介质。为了澄清组织中纳米液滴的相变机制和相变微泡表征并进一步发挥其作为组织中空化核的效用，本项目提出和研究一种组织中基于双频配比聚焦超声的纳米液滴相变控制技术，包括控制相变微泡尺寸分布，成核阈值与区域，实现高效、精细肿瘤组织热消融。重点研究（1）组织内多气体分量微泡消散动力学模型，并原创一种组织中多气体分量微泡尺寸分布声学估计方法；（2）通过改变双频环阵聚焦超声声强配比调控组织中相变成核阈值、区域及微泡尺寸分布；（3）将上述超声调控技术用于肿瘤组织高效精细热消融，经透明仿组织体模及光学观察对照验证后，推进到活体动物肿瘤模型实验研究。本研究有望将声致纳米液滴气化机制、相变微泡表征和相变过程控制及应用研究推进到一个新的高度。

纳米相变液滴因其尺寸小易于进入组织间隙等优势，能够有效提高肿瘤热消融等基于空化效应的超声治疗效率，然而目前纳米相变液滴的机制研究多局限于液体介质。为了澄清组织中纳米液滴的相变机制和相变微泡表征并进一步发挥其作为组织中空化核的效用，本项目提出和研究一种组织中基于双频配比聚焦超声的纳米液滴相变控制技术，包括控制相变微泡尺寸分布，成核阈值与区域，实现高效、精细肿瘤组织热消融。研究了（1）组织内微泡消散动力学模型，并原创一种组织中微泡尺寸分布声学估计方法；（2）通过改变双频环阵聚焦超声声强配比调控组织中相变成核阈值、区域；研究结果将传统的液体中空化研究推进到组织中空化研究，更接近临床实际应用。