Image-Guided High-Intensity Interstitial Ultrasound for Thermal Ablation of Uteri

描述（由申请人提供）：用于子宫肌瘤热消融的高强度间质超声。 良性子宫肿瘤（肌瘤）在临床上表现为高达50%的妇女，通常需要手术切除症状性肌瘤或子宫切除术。考虑生育的女性的治疗选择仅限于侵入性开放性子宫肌瘤切除术，以最好地保持子宫壁的结构完整性;禁忌微创腹腔镜切除。临床上仍然需要一种微创手术方法来替代传统手术方法，该方法具有发病率低、恢复时间短、手术时间短和成本低的优点。最近的微创热技术（冷冻疗法，热消融）的临床研究表明，在减少肌瘤体积和相关症状，同时保持子宫壁的完整性显着的潜力。这些技术的一些局限性包括不能在空间上控制能量输出的分布以符合肌瘤体积，需要多次器械插入的单个治疗体积不足，手术时间长，或者使用可能受到肌瘤与关键组织结构的接近程度的限制。间质超声设备是我们团队正在开发的一项创新技术，用于提供治疗癌症和前列腺BPH的热疗法，具有提供选择性加热模式的动态空间控制，更大的径向热渗透和快速加热时间的能力。我们建议开发这种专门用于治疗子宫肌瘤的超声技术;这种技术有可能提供一种用于治疗子宫肌瘤的上级微创加热技术，具有更准确和彻底的靶向，保护关键的非靶组织（例如，膀胱、肠），更容易接近更多数量的肌瘤，以及更快的手术时间。本STTR I期研究计划的目标是扩展现有技术，并开发新的间质超声施源器设计，具有高功率输出、温度/剂量反馈和空间控制功能，适用于成功治疗子宫肌瘤所需的大体积适形热消融。经验设计、台架实验、生物力学和声学建模以及人体子宫肌瘤组织中的实验测试将用于设计反馈和表征器械性能，以及评估技术和潜在临床可行性。这些结果将应用于概念开发和潜在治疗方法的理解，为II期产品开发和临床实施的最终目标做准备。项目叙述（相关性）。良性子宫肌瘤每年影响美国（和世界各地）数百万妇女，并且是美国每年进行的600，000例子宫切除术中一半以上的原因。子宫肌瘤的估计患病率为25-50%的育龄妇女（目标年龄范围：25-54岁），相当于16-32万妇女在美国每年有近200万新病例诊断。许多希望保留子宫的妇女接受大手术来治疗肌瘤。目前，唯一的微创治疗是子宫动脉栓塞，其具有超出子宫的显著副作用，并且由于栓塞产生的血管变化，对于希望未来生育的女性来说也不是一种选择。拟议中的新的治疗性超声波治疗将避免这些妇女的大手术，并使她们能够更快地重返工作和活动。很有可能，这也会让女性追求生育。此外，这种新的治疗方法可能会导致比目前任何肌瘤手术更少的副作用和并发症。声学治疗的目标人群包括相当大一部分子宫切除术患者，所有将通过栓塞治疗的患者，几乎所有否则将进行子宫肌瘤切除术的患者，以及保守的20-25%现在没有做任何事情的患者。

DESCRIPTION (provided by applicant): High-Intensity Interstitial Ultrasound for Thermal Ablation of Uterine Fibroids. Benign uterine tumors (fibroids) are clinically apparent in up to 50% of women and typically require surgical removal of symptomatic fibroids or hysterectomy. Treatment options for women considering bearing children are limited to the invasive surgical open myomectomy to best maintain structural integrity of the uterine wall; the less invasive laparoscopic removal is contraindicated. There remains a substantial clinical need for a minimally-invasive alternative to traditional surgical approaches with the promise of less morbidity and recovery time, faster procedure time, and lower cost. Recent clinical investigations of minimally-invasive thermal techniques (cryotherapy, thermal ablation) have demonstrated significant potential in reducing fibroid volume and related symptoms, while preserving uterine wall integrity. Some limitations of these techniques include an inability to spatially control the distribution of energy output to conform to the fibroid volume, inadequate single treatment volumes requiring multiple device insertions, long procedural times, or use may be limited by the proximity of a fibroid to critical tissue structures. Interstitial ultrasound devices are an innovative technology under development by our group for delivering thermal therapy for treating cancer and prostate BPH, with demonstrated capabilities to provide dynamic spatial control of selective heating patterns, greater radial thermal penetration, and fast heating times. We propose to develop this ultrasound technology specifically for the treatment of uterine fibroids; this technology has potential to provide a superior minimally-invasive heating technique for treating uterine fibroids with the promise of more accurate and thorough targeting, protection of critical non-targeted tissue (e.g., bladder, bowel), more accessibility to a larger number of fibroids, and faster procedure times. The objective of this STTR Phase I research plan is to extend existing technology and develop new interstitial ultrasound applicator designs with high-power output, temperature/dose feedback, and spatial control capabilities specific for conformal thermal ablation of large volumes required for successful treatment of uterine fibroids. Empirical design, bench experiments, biothermal and acoustic modeling, together with experimental testing in human uterine fibroid tissue will be used for design feedback and to characterize device performance, as well as assess the technical and potential clinical feasibility. These results will be applied to the conceptual development and understanding of potential treatment approaches in preparation for the ultimate goal of product development and clinical implementation during Phase II. Project Narrative (Relevance). Benign uterine fibroid tumors affect millions of women each year in the U.S. (and around the world), and are the cause of more than half of the 600,000 hysterectomies performed annually in the U.S. There is a true clinical need for effective therapy with improved quality of life that is more favorable than existing treatment options. Direct costs for fibroid treatments exceed $2 billion annually in the U.S. The estimated prevalence of uterine fibroids is 25-50% of women of reproductive age (target age range: 25-54 years old), corresponding to 16-32 million women in the U.S. There are nearly 2 million new cases diagnosed each year. Many women who wish to retain their uterus undergo a major surgical procedure to treat their fibroids. Currently, the only minimally-invasive treatment is uterine artery embolization, which has significant side effects that go beyond the uterus and are also not an option for women who desire future childbearing due to the vascular changes the embolization produces. The proposed new therapeutic ultrasound treatment would avoid major surgery for these women as well as allow them to return to work and activities much faster. In all likelihood, it would allow women to pursue reproduction as well. Further, this new treatment will likely result in far less side effects and complications than any current procedure for fibroids. The target population for acoustic therapy consists of a sizeable fraction of the hysterectomy patients, all patients who would be treated by embolization, nearly all of those that would otherwise have had myomectomy, and conservatively 20-25% of those who now have nothing done.