光声空化微血管定位损伤的物理机制、原位评价与活体监控

Cavitation damage on micro-vessel has the great potential applications in the tumor angiogenesis histotripsy and the localized drug delivery. In this project, photoacoustic cavitation is proposed based on the nucleation theory to reduce the energy threshold and improve the temporal and spatial resolution of cavitation damage. After the theoretical modeling, in situ evaluation and in vivo experiments, the study makes the precise and targeted cavitation damage on micro-vessel feasible, reveals its nucleation, mechanical and biological effects, and then forms the theoretical and technological basis for an experimental and scientific instrument of the image guided and monitored photoacoustic cavitation damage on the micro vessels in small animals. The research is focused on: ①The simulation of photoacoustic cavitation nucleation and bubble dynamics on the elastic boundary is to reveal the cavitation behavior and the effects of photo/acoustic parameters. ②The light and acoustic cofocal microscopy with high speed imaging of photoacoustic cavitation on in situ micro-vessel model would be built completely to discuss the interaction between photoacoustic cavitation bubble and vessel and its biological effects. ③The image-guided photoacoustic cavitation would be realized in the nude mice spine tumor model in vivo. Moreover, the cavitation process is to be monitored by ultrasound cavitation imaging via analyzing the special acoustic signal during and after photoacoustic cavitation.

空化效应对微血管的可控损伤在肿瘤新生血管毁损和局部释药治疗等领域具有重要的应用价值。本项目基于空化生成理论，提出光声空化方法克服声空化能量阈值高和空间分辨率低等局限性，通过理论模型、原位评价和活体实验研究，使空化微血管精准定位损伤成为可能，澄清光声空化成核机制及其空化泡与微血管相互作用的力/生物学效应，为形成图像引导和监控的光声空化微血管损伤小动物科学实验仪器系统提供理论与关键技术支撑。主要研究：①光声空化成核及其在弹性界面泡动力学理论仿真，澄清光声空化成核及其泡动力学行为和影响因素；②提出并建立原创的光声空化共焦显微高速成像-微血管原位灌注实验系统，结合生物学评价方法，探讨弹性血管壁附近光声空化泡对血管壁的力学作用模式和生物学效应；③在裸鼠脊背肿瘤模型上实现图像引导的光声空化微血管损伤，提取光声空化泡特征声学信号，基于超声空化成像实现其监控评价。

光和声作为生物医学工程领域常见的两种高效能量模式，其协同作用在光声空化、成像以及联合诊疗等领域具有重要的发展前景。本项目以光声空化效应对微血管的可控损伤为切入点，分别从空化生成理论、空化与微血管及细胞相互作用机制和力/生物学效应以及光声联合抗肿瘤小动物研究三个层面，主要完成了以下研究工作：①在理论研究方面，本项目完成了光声空化成核及其在弹性界面泡动力学理论仿真，澄清光声空化成核及其泡动力学行为和影响因素；②在原位实验方面，项目建立了原创的光声空化共焦显微高速成像-微血管原位灌注实验系统，结合生物学评价方法，探讨了弹性血管壁附近空化泡对血管壁的力学作用模式和生物学效应，提出了空化泡所造成的微血管内陷的微血管损伤机制，研究成果被美国物理协会和教育部科技发展中心等国内外媒体评价在“栓塞-药物释放”双模肿瘤治疗中具有重要的应用前景；③在动物实验方面，本项目在裸鼠肿瘤模型上实现了光声联合抗肿瘤研究，并提取了空化泡特征声学信号，基于超声空化成像实现其监控评价。本项目按计划完成了主要研究目标和内容，澄清了光声空化成核机制及其空化泡与微血管相互作用的力/生物学效应，为形成图像引导和监控的光声空化微血管损伤小动物科学实验仪器系统提供理论与关键技术支撑。