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

超声引导内阈组织解剖学用于子宫肌瘤的无创消融

基本信息

批准号：
10684104
负责人：
Eli Vlaisavljevich
金额：
$ 23.1万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10684104
关键词：
Ablation Acoustics Acute Adoption Adverse event Aftercare Age Animal Model Behavior Benign Cartilage Chronic Cicatrix Convalescence Development Disease Excision Fibroadenoma Fibroid Tumor Focused Ultrasound Focused Ultrasound Therapy Goals Hospitalization Human Hysterectomy Immune response Inflammatory Response Leiomyoma Magnetic Resonance Imaging Mechanics Methods Modeling Necrosis Nerve Operative Surgical Procedures Outcome Patient-Focused Outcomes Physiologic pulse Procedures Property Recovery Research Resolution Rodent Model Safety Shapes Shock Structure Symptoms Techniques Tendon structure Thermal Ablation Therapy Time Tissues Translations Ultrasonography Uterine Fibroids Uterus Woman Work bile duct clinical application experimental study image guided improved in vivo in vivo evaluation millimeter preservation prevent rapid technique real-time images reproductive reproductive function soft tissue tissue phantom treatment optimization treatment response tumor ultrasound

项目摘要

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.

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。热的 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。