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

项目摘要 本研究的目的是开发一种非热聚焦超声（FUS）的内阈值组织破坏术 子宫肌瘤的非侵入性消融技术。子宫肌瘤（平滑肌瘤）是最常见的 生殖年龄妇女的良性肿瘤，导致超过25万人住院，20万人死亡。 每年都要做切除术。子宫肌瘤的金标准是子宫切除术，这是一种外科手术， 需要延长住院时间和恢复时间，并导致生殖功能丧失。热 FUS已成为一种非侵入性的方法，用于管理和保护子宫功能。然而，在这方面， 由于热扩散引起的并发症，依赖MRI进行图像引导，治疗时间缓慢， 治疗后纤维瘤的再吸收限制了热FUS的广泛使用。这项建议 开发了用于子宫肌瘤消融的内在阈值组织摧毁术。虽然组织解剖学显示 在许多临床应用中克服热消融局限性的潜力，该技术以前 在高度纤维化的组织中效果较差，这迄今为止阻止了组织碎石术的应用。 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， 组织摧毁术可以使用固有阈值组织摧毁术技术有效地消融人子宫肌瘤。在 本课题将探讨快速消融子宫肌瘤的最佳组织摧毁治疗方法 在实时超声图像引导下在目标1中，我们将比较组织破坏空化气泡云 多周期（冲击散射组织破坏术）和单周期（固有）产生的行为和组织消融 阈值组织摧毁术）方法，其使用大范围的潜在组织摧毁术脉冲参数。实验将 在机械可调的组织模型中进行，该模型模拟纤维组织的特性以及 使用切除的人子宫肌瘤的体内实验。在目标2中，我们将测试内源性药物的体内安全性和有效性。 在小动物模型中进行阈值组织摧毁术消融。这些目标的成功实现将表明， TEH用于子宫肌瘤非侵入性治疗的安全性和有效性。

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.