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

• 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
• 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

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.

项目摘要 该项目的目的是开发固有的阈值组织疗法作为非热为重点超声（FUS） 子宫肌瘤非侵入性消融的技术。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250,000次入院和200,000 每年子宫切除术。子宫肌瘤的金标准是子宫切除术，这是一种手术程序 需要延长住院和恢复时间，并导致生殖功能的丧失。热的 FUS已成为一种用于子宫功能管理和保护的非侵入性方法。然而， 由于热蔓延而引起的并发症，对图像引导的MRI依赖，治疗时间缓慢和缓慢 治疗后的肌瘤的吸收限制了热液体的广泛使用。这个建议 为子宫肌瘤的消融开发固有的阈值组织疗法。虽然组织疗法已显示 在许多临床应用中克服热消融的局限性的潜力，该技术以前具有 被证明在高度纤维组织中的有效性较低，到目前为止，这阻止了组织疗法 开发用于治疗子宫肌瘤。最近，我们的团队完成了一项概念证明研究，证明了 这种组织疗法可以使用固有的阈值组织疗法技术有效地烧毁人子宫肌瘤。在 该项目，我们将研究子宫肌瘤快速消融的最佳组织肌肉治疗方法 在实时超声图像下。在AIM 1中，我们将比较Histotipsy空化气泡云 由多周期（震动散射的组织疗法）和单周（固有的）产生的行为和组织消融 使用多种潜在的组织肌肉脉冲参数的阈值组织练习方法。实验会 在模仿纤维组织的特性以及EX的特性中进行机械可调的组织幻象 使用切除的人子宫肌瘤进行体内实验。在AIM 2中，我们将测试体内安全性和内在功效 小动物模型中的阈值组织疗法消融。这些目标的成功完成将证明 TEH对子宫肌瘤非侵入性治疗的安全性和功效。