增强焦区空化机制的共焦双倍频分裂焦点聚焦超声手术新方法

The innovation research works of this project include two aspects, one is improving the effectiveness and safety of histotripsy when treat the tissues of variety mechanical properties with higher efficiency, another is evidently increase of efficiency in pHIFU thermal ablation, and the detailed research works are listed as follows: Firstly, an approach of enhanced cavitation activities in spherical confocal region using dual frequency of harmonic superimposition which will bring up split foci sited in focus plane is proposed. The pHIFU thermal-ablation experiments will be implemented to explore the enhanced cavitation mechanism of strong interference between cavitation clouds at (or near) foci, the conditions of optimal cavitation inception and boiling mechanisms. Secondly, a novel histotripsy strategy with pulses of hundred microseconds combined with an approach of dual frequency of harmonic superimposition bringing up split foci along propagation axial is proposed. The driving power level to each frequency will be confirmed and the nonlinear models will be established. Ex vivo experiments with tissues of different mechanical properties will then be implemented using this combined strategy to explore the enhanced cavitation and boiling mechanisms. Further, the experiments of rabbit model which includes the liver, kidney and VX-2 tumor implanted in the kidney will be implemented to testify the effectiveness, high efficiency and safety of this combined strategy. Finaly, the histotripsy strategy with pulses of hundred microseconds combined with the approach of dual frequency of harmonic superimposition bringing up split foci sited in focus plane is proposed. Ex vivo and in vivo experiments of animal organ tissues will be implemented to obtain the means with higher histotripsy efficiency. Hopefully, based on the research works of this project, the histotripsy and pHIFU thermal ablation approaches with high efficiency will be established, and be of great value in academic and clinical applications.

对Histotripsy(组织毁损)，在安全性提升的情况下更有效和高效地进行各种力学特性组织的治疗，以及显著提高pHIFU治疗效率而开展的创新方法研究，包括：(1)提出球面共焦双倍频焦平面分裂焦点空化增效机制研究；研究并揭示pHIFU热治疗的分裂焦点处空化群强相互作用、优化空化发生的增效机制。(2)提出百微秒脉冲Histotripsy共焦双倍频声轴分裂焦点的方法研究；获得增强焦区声强控制方法；建立非线性模型；对各种力学特性组织的治疗研究，揭示分裂焦点处空化群相互作用和沸腾气泡增效机制；针对兔肾、肝和肾移植VX-2肿瘤进行有效、高效和安全治疗研究。(3)提出百微秒Histotripsy双倍频焦平面分裂焦点以提高治疗效率的研究；对离体和活体动物组织实验研究，获得高效Histotripsy方法。项目创新性方法研究对于Histotripsy和pHIFU热消融的高效、安全治疗具有重要学术和应用价值。

项目在国际前沿研究领域展开了创新性方法探索；本项目“强焦区空化机制的共焦双倍频分裂焦点聚焦超声手术方法”的研究具有重要的学术和应用意义。.项目按研究计划①首先开展了提出的双二倍频百微秒脉冲两阶段的高效组织毁损方法研究；离体猪肾脏治疗获得有效的histotripsy液化损伤呈 “长泪滴状” 尺寸为5.8 mm ×2 mm，研究揭示增强的非线性、空化泡和沸腾气泡机制。 ②非线性研究：包括双2倍频和双3倍频声轴增强和扇阵声场控制、相位差优化、多场非线性、HIFU声压检测和双频微泡组织模型。③拓展研究提出用毫秒长脉冲组结合双二倍频对脑出血大血肿液化毁损的初步实验；实验得到了液化碎片尺寸2-6微米、达到了高效和更精准的治疗目的。④项目重点开展了1.2/2.4 MHz扇形阵焦平面分裂焦点模式Histotripsy；研究分百微秒两阶段和拓展的毫秒长两阶段治疗方式两种，研究并揭示其中非线性增效机制，离体组织肾脏的组织液化损伤尺寸7.5 mm*5.5 mm (轴向*径向)，H＆E染色证实了靶区组织彻底均匀化并且边界锐利。⑤项目进行了声轴增强焦点双3倍频叠加组织毁损研究，在相位差60度时焦点处正、负压峰值相遇，最有利于空化产生和剧烈崩塌；结果显示毫秒长两阶段组织毁损是百微秒的损伤的2倍。⑥拓展研究进行256相控阵HIFU组织毁损初步研究，在相控阵的算法方面：为解决经颅多焦点无栅瓣增大扫描范围的问题，提出了随机稀疏阵联合粒子群优化焦点模式的相控阵算法。⑦针对活体兔肾脏的组织毁损研究近期取得重要进展，采用B超引导的1.1/2.2MHz毫秒长两阶段的治疗模式，获得损伤尺寸为7.7 mm*3.8 mm。⑧最后，项目在组织治疗前后粘弹性研究取得了进展；在脉冲声辐射力剪切波2D-FT理论基础上提出并构建了基于卷积定理的k空间方法进行定量粘弹性实验，方法中还包含采用2 D-FT和模型拟合方法。