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

项目总结 本项目的目标是发展一种非热聚焦超声(Fus)的固有阈值组织学。 子宫肌瘤非侵入性消融技术。子宫肌瘤(平滑肌瘤)最常见 育龄妇女良性肿瘤，导致250,000多人入院和200,000人住院 每年都要做子宫切除术。子宫肌瘤的黄金标准是子宫切除术，这是一种可以 需要延长住院和康复时间，并导致生殖功能丧失。热能 FUS已经成为一种非侵入性的子宫功能管理和保存方法。然而， 热扩散引起的并发症，依靠MRI进行影像指导，治疗时间慢，速度慢 治疗后肌瘤的吸收限制了热FUS的广泛应用。这项建议 开发用于子宫肌瘤消融术的本征阈值组织学。虽然组织试验表明 为了克服热消融在许多临床应用中的局限性，该技术以前已经 已被证明在高纤维组织中效果较差，到目前为止，这阻止了组织尿路感染 用于治疗子宫肌瘤的药物。最近，我们团队完成了一项概念验证研究，演示了 利用本征阈值组织电切技术，组织电切术可以有效地切除人子宫肌瘤。在……里面 本项目将探讨子宫肌瘤快速消融的最佳组织学治疗方法 在实时超声图像引导下。在目标1中，我们将比较组织摩擦空化气泡云 多周期(冲击-散射组织摩擦)和单周期(固有)产生的行为和组织消融 阈值组织摩擦)方法使用广泛的潜在组织摩擦脉冲参数。实验将会 在可机械调节的组织模体中进行，模拟纤维组织的特性以及EX 用摘除的人子宫肌瘤进行活体实验。在目标2中，我们将测试体内安全性和有效性 在小动物模型中进行阈值组织化学消融。这些目标的成功实现将证明 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.