摘要：Histotripsy是一种基于高强度聚焦超声（HIFU）的非侵入性、非热、非电离的机械消融技术，通过空化效应将靶组织液化并转化为亚细胞碎片。自20年前首次提出以来，该技术因其精准性、安全性和潜在的免疫调节效应，在肿瘤治疗、心血管疾病及骨肿瘤等领域展现出广阔前
引言
Histotripsy是一种基于高强度聚焦超声（HIFU）的非侵入性、非热、非电离的机械消融技术，通过空化效应将靶组织液化并转化为亚细胞碎片。自20年前首次提出以来，该技术因其精准性、安全性和潜在的免疫调节效应，在肿瘤治疗、心血管疾病及骨肿瘤等领域展现出广阔前景。本文基于40篇最新文献，系统综述histotripsy的技术原理、临床应用、研究进展及未来挑战。一、技术原理与分类
1. 物理机制
Histotripsy通过短脉冲、高振幅的超声波诱导空化效应，产生微气泡云并使其剧烈振荡，从而机械性破坏细胞结构（文献2、10）。根据能量传递方式不同，主要分为以下两类：
- 空化云histotripsy：依赖空化气泡的动态破裂直接破坏组织（文献5）。
- 沸腾histotripsy：通过快速加热靶组织至沸腾温度，结合声波机械力实现消融（文献5、15）。
2. 技术优势
- 非热效应：避免热损伤对周围组织的副作用（文献1、9）。
- 实时成像引导：消融边界清晰，残留瘢痕极小（文献1、16）。
- 免疫调节潜力：消融后释放损伤相关分子模式（DAMPs），激活抗肿瘤免疫（文献8、12）。二、临床应用进展
1.肝脏肿瘤
- 首个人体试验（THERESA试验）：肝组织消融后1-2个月完全吸收，肿瘤标志物持续下降（文献3）。
- #HOPE4LIVER试验：FDA批准用于肝肿瘤治疗，证实其安全性与有效性（文献19）。
- 远端效应：病例报告显示，未治疗的转移灶体积缩小，可能与免疫激活相关（文献25）。
2. 脑部疾病
- 脑出血液化：经颅磁共振引导histotripsy（tcMRgHt）可安全清除血肿（文献31-33）。
- 神经胶质瘤：动物模型中，治疗后肿瘤活性显著降低，MRI显示消融区域边界清晰（文献22、29）。
3. 骨与软组织肿瘤
- 骨肉瘤：犬类模型中，histotripsy可消融自发骨肿瘤，为人类肢体挽救治疗提供参考（文献17、39）。
-肌腱消融：弹性各向异性组织（如肌腱）需结合双频超声提升消融效率（文献24、27）。
4.其他领域
- 心血管疾病：用于血栓溶解和心肌消融（文献18）。
- 子宫肌瘤：离体实验中，消融体积与病理结果高度一致（文献34）。三、技术挑战与优化策略
1. 组织特异性限制
- 弹性组织（如肌腱）和纤维化肿瘤（如胆管癌）对空化效应抵抗性强，需调整脉冲参数（文献24、36）。2. 像差校正
- 腹部治疗中，腹壁导致声波畸变，需开发自适应聚焦算法（文献6、16）。3. 免疫效应机制
- 尽管临床前研究显示histotripsy可激活免疫微环境，但其长期疗效需结合免疫检查点抑制剂验证（文献8、12、37）。四、未来发展方向
1. 多学科联合治疗：结合免疫疗法或化疗，增强全身抗肿瘤效应（文献12、37）。
2. 设备创新：研发内镜式双频探头（文献40）和经颅专用系统（文献26），拓展适应症范围。
3. 标准化评估体系：建立基于影像和生物标志物的疗效评价标准（文献15、29）。
结论
Histotripsy作为一种革命性消融技术，凭借其非侵入性和免疫调节潜力，正在重塑肿瘤及多种疾病的治疗模式。尽管在组织穿透性、标准化治疗参数等方面仍需优化，其临床转化成果（如肝肿瘤FDA获批）已为未来应用奠定基础。随着技术迭代与机制研究的深入，histotripsy有望成为多学科精准医疗的核心工具。参考文献
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来源：医学镜界
