Image-Guided Transurethral HIFU for Genitourinary Therapy

摘要 女性压力性尿失禁（SUI）是骨盆底顺应性的增加，导致 尿道压力降低，通常通过分娩，并在腹部手术期间表现为尿漏 株SUI对妇女的健康有重大影响，包括与增加的 萧条治疗选择仅限于侵入性手术插入带状植入物，这限制了患者的生存时间。 尿道的灵活性。在尿道周围组织中注射膨胀剂是一种长期有效的方法， 临时治疗。药品相对较新，价格高得令人望而却步，而且没有任何记录 长期疗效和负面副作用可能发生。大约有1 400万妇女被降级为 一整天都穿着吸收垫或尿布的姑息性方法。存在大量临床需求 作为传统手术方法的非侵入性替代方法， 时间、更快的手术时间和更低的成本。微创热疗的临床研究进展 技术已经证明，骨盆组织的靶向热修饰和硬化可以减少 SUI的症状这些技术已经显示出希望，但比目前的外科手术更具侵入性。 选择，效果不太好。我们的II期开发研究显示了令人鼓舞的体内结果， 我们创新的基于治疗超声导管的无创技术可以有效地提供热 在不损伤周围组织（阴道和尿道）的情况下在骨盆内筋膜的靶组织处进行治疗 壁），根据组织病理学分析，具有提供动态空间控制的能力， 选择性加热模式、良好控制的径向热渗透以及快速的治疗时间。相比 与现有的热处理方法相比，我们的第二阶段研究结果清楚地表明，在技术上取得了重大进展 和方法治疗SUI的承诺，更准确和彻底的目标热诱导 胶原再生，保护关键的非靶组织（例如，尿道和阴道粘膜），短 手术时间，从而增加了对大量SUI患者的可及性。的目的 IIB期计划是设计-冻结我们的治疗施源器设计，然后使用我们的 超声SUI导管和FDA 510（k）批准的TheraVision®系统的数据支持后续临床 在FDA指导下进行研究，并进一步围绕该技术建立更多强大的知识产权。 将进行市场分析，以制定商业化战略。器械设计，台架 实验，生物学和声学建模，以及在人类女性和 骨盆尸体研究和绵羊GU道的体内GLP合规性研究，结合工作流程研究 将进行冻结器械设计，广泛表征器械性能，并应用于 潜在的治疗方法，为最终的产品定型和临床 实施.器械将在我们现有的符合ISO的质量管理体系下生产。

Abstract Stress urinary incontinence (SUI) in women is an increase of pelvic floor compliance which results in decreased urethral pressure, typically through childbirth, and presents as urine leakage during abdominal strain. SUI has significant impact on women’s health, including an association with increased levels of depression. Curative options are limited to the invasive surgical insertion of a tape implant which limits the mobility of the urethra. Bulking agents injected in the peri-urethral tissue are a longstanding effective but temporary treatment. Pharmaceuticals are relatively new, prohibitively expensive, and there is no track record of long-term efficacy and negative side effects can occur. Approximately 14 million women are relegated to the palliative approaches of wearing absorptive pads or diapers through the day. A substantial clinical need exists for a noninvasive 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 have demonstrated targeted thermal modification and stiffening of pelvic tissue can reduce symptoms of SUI. These techniques have shown promise, but are more invasive than the current surgical options and are less effective. Our Phase II development study showed encouraging in vivo results suggesting that our innovative therapeutic ultrasound catheter based noninvasive technology can efficiently deliver thermal therapy at the target tissue of endopelvic fascia without damaging surrounding tissue (vaginal and urethal wall), based on histopathological analysis, with demonstrated capabilities to provide dynamic spatial control of selective heating patterns, well-controlled radial thermal penetration, and fast treatment times. In comparison to existing thermal approaches, our Phase II results clearly demonstrate a significant advance in technology and approach for treating SUI with the promise of more accurate and thorough targeting of heat-induced collagen regeneration, protection of critical non-targeted tissue (e.g., urethral and vaginalmucosa), short procedure times, and thereby increasing accessibility to a larger number of SUI patients. The objective of this Phase IIB plan is to design-freeze our therapy applicator design and then conduct a GLP in-vivo study with our ultrasound SUI catheter and FDA 510(k) cleared TheraVision® system for data to support a follow-on clinical study under FDA Guidance and to further build additional strong intellectual property around the technology. Market analyses will be conducted to develop strategies leading to commercialization. Device design, bench experiments, biothermal and acoustic modeling, together with experimental testing in both human female pelvis cadaveric studies and an in-vivo GLP compliant study in ewes GU tract, combined with workflow study will be conducted to freeze device design, extensively characterize device performance, and applied to potential treatment approaches in preparation for the ultimate goal of product finalization and clinical implementation. Devices will be manufactured under our existing ISO compliant Quality Management System.