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

描述(申请人提供)：高强度组织间超声用于子宫肌瘤的热消融。良性子宫肿瘤(子宫肌瘤)在临床上可见于高达50%的女性，通常需要手术切除有症状的子宫肌瘤或子宫切除术。对于考虑生育的妇女，治疗选择仅限于侵入性的开腹子宫肌瘤切除术，以最好地保持子宫壁的结构完整性；禁止使用侵入性较小的腹腔镜手术。临床上仍然需要一种替代传统手术方法的微创方法，以减少发病率和恢复时间，缩短手术时间，降低成本。最近的临床研究表明，微创热疗技术(冷冻治疗、热消融)在减少子宫肌瘤体积和相关症状方面具有巨大潜力，同时还能保持子宫壁的完整性。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，不足以满足需要多个装置插入的单一治疗体积，较长的程序时间，或者使用可能受到肌瘤接近关键组织结构的限制。间质超声设备是我们团队正在开发的一项创新技术，用于治疗癌症和前列腺增生症，具有提供选择性加热模式的动态空间控制、更大的径向热穿透和快速加热时间的能力。我们建议开发这项专门用于治疗子宫肌瘤的超声技术；这项技术有可能为治疗子宫肌瘤提供一种优越的微创加热技术，承诺更准确和彻底的靶向，保护关键的非靶向组织(如膀胱、肠道)，更容易接触到更多的肌瘤，以及更快的手术时间。这项STTRI期研究计划的目标是扩展现有技术，开发具有高功率输出、温度/剂量反馈和空间控制能力的新组织间超声辐射器设计，专门用于成功治疗子宫肌瘤所需的大体积适形热消融。经验性设计、台式实验、生物热学和声学建模，以及在人类子宫肌瘤组织中的实验测试将用于设计反馈和表征设备性能，以及评估技术和潜在的临床可行性。这些结果将应用于概念开发和对潜在治疗方法的理解，为第二阶段的产品开发和临床实施的最终目标做准备。良性子宫肌瘤每年在美国(和世界各地)影响数百万女性，在美国每年进行的60万例子宫切除术中，有一半以上是良性子宫肌瘤的原因。临床上确实需要有效的治疗，以改善生活质量，这比现有的治疗方案更有利。在美国，每年治疗子宫肌瘤的直接费用超过20亿美元。据估计，子宫肌瘤的患病率在育龄妇女(目标年龄范围：25-54岁)中占25%-50%，相当于美国的1600万-3200万妇女。每年有近200万新诊断病例。许多希望保留子宫的女性都要接受大手术来治疗子宫肌瘤。目前，唯一的微创治疗是子宫动脉栓塞术，它具有超出子宫的显著副作用，也不是由于栓塞术产生的血管变化而希望未来生育的女性的选择。拟议的新治疗性超声波治疗将避免对这些妇女进行大手术，并使她们能够更快地重返工作和活动岗位。很有可能，它也会让女性追求生殖。此外，这种新的治疗方法可能会比目前任何治疗肌瘤的方法产生的副作用和并发症都要少得多。声学治疗的目标人群包括相当大一部分子宫切除术患者，所有将接受栓塞术的患者，几乎所有原本将接受子宫肌瘤切除术的患者，以及保守地占现在无所作为的患者的20%-25%。

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.