Ultrasound-guided Intrinsic Threshold Histotripsy for the Non-invasive Ablation of Uterine Fibroids

项目概要 该项目的目标是开发内阈组织解剖学作为非热聚焦超声 (FUS) 子宫肌瘤无创消融技术。子宫肌瘤（平滑肌瘤）是最常见的 育龄妇女良性肿瘤，导致超过 250,000 人住院，200,000 人死亡 每年进行子宫切除术。子宫肌瘤的黄金标准是子宫切除术，这是一种外科手术， 需要延长住院和康复时间，并导致生殖功能丧失。热学 FUS 已成为一种管理和保护子宫功能的非侵入性方法。然而， 热扩散引起的并发症、依赖 MRI 进行图像引导、治疗时间慢以及治疗速度慢 治疗后肌瘤的吸收限制了热FUS的广泛使用。这个提议 开发了用于子宫肌瘤消融的内在阈值组织解剖学。虽然组织病理学显示 该技术有可能克服许多临床应用中热消融的局限性 已被证明在高纤维组织中效果较差，迄今为止这阻碍了组织解剖学的应用 开发用于治疗子宫肌瘤。最近，我们的团队完成了一项概念验证研究，证明 组织解剖学可以使用内在阈值组织解剖学技术有效地消融人类子宫肌瘤。在 在这个项目中，我们将研究快速消融子宫肌瘤的最佳组织解剖治疗方法 在实时超声图像引导下。在目标 1 中，我们将比较组织解剖空化气泡云 多周期（冲击散射组织解剖）和单周期（内在 阈值组织解剖）方法使用各种潜在的组织解剖脉冲参数。实验将 可以在机械可调的组织模型中进行，该模型模仿纤维组织的特性以及前 使用切除的人子宫肌瘤进行体内实验。在目标 2 中，我们将测试内在的安全性和有效性 小动物模型中的阈值组织解剖消融。这些目标的成功实现将证明 TEH 无创治疗子宫肌瘤的安全性和有效性。

PROJECT SUMMARY The goal of this project is to develop intrinsic threshold histotripsy as a non-thermal focused ultrasound (FUS) technique for the non-invasive ablation of uterine fibroids. Uterine fibroids (leiomyomas) are the most common benign tumors in women of reproductive age, resulting in over 250,000 hospital admissions and 200,000 hysterectomies annually. The gold standard for uterine fibroids is hysterectomy, a surgical procedure that requires extended hospitalization and recovery time, and results in the loss of reproductive function. Thermal FUS has emerged as a non-invasive method for the management and conservation of uterine function. However, complications due to thermal spread, reliance on MRI for image-guidance, slow treatment times, and slow resorption of the fibroids after treatment have limited the widespread use of thermal FUS. This proposal develops intrinsic threshold histotripsy for the ablation of uterine fibroids. While histotripsy has shown the potential to overcome limitations of thermal ablation in many clinical applications, the technique has previously been shown to be less effective in highly fibrous tissues, which has thus far prevented histotripsy from being developed for treating uterine fibroids. Recently, our team completed a proof-of-concept study demonstrating that histotripsy can effectively ablate human uterine fibroids using intrinsic threshold histotripsy techniques. In this project, we will investigate the optimal histotripsy treatment methods for the rapid ablation of uterine fibroids under real-time ultrasound image-guidance. In Aim 1, we will compare the histotripsy cavitation bubble cloud behavior and tissue ablation generated by multi-cycle (shock-scattering histotripsy) and single-cycle (intrinsic threshold histotripsy) methods using a wide range of potential histotripsy pulsing parameters. Experiments will be conducted in mechanically-tunable tissue phantoms that mimic the properties of fibrous tissue as well as ex vivo experiments using excised human uterine fibroids. In Aim 2, we will test in vivo safety and efficacy of intrinsic threshold histotripsy ablation in a small animal model. The successful completion of these aims will demonstrate the safety and efficacy of TEH for the non-invasive treatment of uterine fibroids.