高分辨低伪影脉冲HIFU超声被动空化成像与相变微泡/空化瞬态协同作用机制研究

Aiming at two problems, including that the existing passive cavitation mapping technique can not real-time monitoring of pulsed HIFU therapy process mediated by phase-change droplets with high resolution and low artifacts and the transient synergistic mechanisms between phase-change microbubbles and cavitation are not clear, this project proposes and investigates the following theoretical methods and techniques. Firstly, a high-resolution and low-artifacts passive cavitation mapping technique, which is based on dual/multiple apodization with cross correlation by extracting element randomly/alternately and doubly constrained robust adaptive beamformer, is proposed for real-time monitoring of pulsed HIFU therapy process mediated by phase-change droplets. Secondly, a cavitation energy/frequency space-time distribution mapping technique with microsecond time resolution, which is based on empirical mode decomposition and Wiener inverse filtering deconvolution, is proposed and combined with phase-change microbubbles ultrasound imaging to study the transient synergistic mechanisms between phase-change microbubbles and cavitation and their influences on damage efficiency and accuracy. Finally, the feasibility of using high-resolution and low-artifacts passive cavitation mapping technique to real-time monitor the pulsed HIFU tumour therapy process mediated by phase-change droplets is confirmed based on the nude mice model, and the transient synergistic mechanisms between phase-change microbubbles and cavitation and their influences on therapeutic effect are analyzed in vivo. This project enables the adjustment and optimization of the therapy plans in pulsed HIFU mediated by phase-change droplets, and also promotes the development of pulsed HIFU therapy technique, therefore laying a foundation for realizing high-efficiency, fine, and safe ultrasound tumour therapy.

本项目针对（1）现有被动空化成像无法对相变液滴介导脉冲HIFU治疗过程进行高分辨低伪影实时监控和（2）相变微泡/空化瞬态协同作用机制不清楚两方面问题，提出和研究：（1）基于阵元随机/交叉抽取双重/多重变迹互相关和双约束鲁棒自适应波束合成的高分辨低伪影被动空化成像技术，以实时监控相变液滴介导脉冲HIFU治疗过程；（2）基于经验模态分解和维纳逆滤波解卷积的微秒时间分辨空化能量/频率时空分布成像技术，并结合相变微泡超声成像，研究相变微泡/空化瞬态协同作用机制及其对损伤效率和精准程度的影响；（3）基于裸鼠肿瘤模型证实高分辨低伪影被动空化成像技术实时监控相变液滴介导脉冲HIFU肿瘤治疗过程的可行性，并分析活体条件下相变微泡/空化瞬态协同作用机制及其对治疗效果的影响。使相变液滴介导脉冲HIFU治疗方案的调控与优化成为可能，推动脉冲HIFU治疗技术的发展，并为实现高效、精细、安全超声肿瘤治疗奠定基础。

相变纳米液滴介导脉冲高强度聚焦超声（HIFU）在肿瘤治疗方面具有广阔的应用前景，空化的监控成像及机制研究是实现安全精准高效肿瘤治疗的根本保障。超声被动空化成像可在治疗过程中对空化进行无干扰的实时监控，但存在分辨率差伪影高且难以实现微秒级成像的问题；同时，相变纳米液滴介导脉冲HIFU治疗过程中空化的物理机制并不明晰。本项目针对这些问题开展研究，取得了重要进展，主要包括：1）发展了基于双重/多重变迹互相关与自适应波束合成的超声被动空化成像方法，有效克服了分辨率差伪影高的问题，为治疗过程空化监控成像提供了有力手段；2）发展了微秒级多尺度空化时空成像及空化特征图谱计算方法，使得空化时空瞬态演变过程的成像及定征成为可能，为空化瞬态物理机制研究提供了有力手段；3）对相变纳米液滴介导脉冲HIFU中的空化进行了监控成像并对其物理机制进行了定量研究，分析了脉冲重复频率和声压对空化记忆效应的影响，为调控优化治疗方案奠定了基础。本项目为实现治疗过程中空化的高空时分辨监控成像提供了新方法，并为澄清相变纳米液滴介导脉冲HIFU治疗的空化物理机制提供了帮助，使得安全精准高效的肿瘤治疗成为可能。