SBIR Phase II: High Surface Area (HSA) Intraluminal Cryoablation for the Treatment of High-Risk Patients with Gallstone Disease

这个小型企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力将是开发第一个微创冷冻消融解决方案来治疗胆囊疾病的高危患者。目前治疗胆囊疾病的金标准是手术切除胆囊。虽然这种手术对健康患者效果良好，但全身麻醉的使用已被证明会增加患有潜在慢性疾病的老年患者的并发症，导致美国医疗保健系统每年花费6.75亿美元。此外，病情严重无法手术的患者没有明确的治疗方案，这突出表明需要一种更安全的替代方案。I期研究证明，能够通过微创导管系统安全输送冷冻消融能量，在不切除的情况下使猪胆囊长期去功能化。第二阶段的工作重点是冷冻消融系统的产品开发和临床输送参数的优化。该技术的目标是让临床医生为他们的患者提供手术的好处，而没有风险。这个小企业创新研究（SBIR）二期项目提出继续开发能够安全有效靶向胆囊的微创冷冻消融系统。冷冻消融系统的初步试验已证明能够在整个胆囊腔中均匀产生致死性冷冻消融温度（-20℃），导致猪动物在术后长达60天的持久胆囊瘢痕形成和功能丧失。本项目的关键技术目标是开发导引器、冷冻消融导管和控制系统的工业设计，以提高临床可用性和可制造性，进一步测试和表征临床输送参数以告知治疗计划，提高传感器可靠性和控制系统响应时间以优化安全性，并在体内验证集成系统以证明具有优化的给药参数的系统性能。该系统将在热负荷下的先进台式胆囊模型、离体胆囊组织和体内慢性动物模型中进行评价，以优化和确认冷冻消融导管和集成控制系统。该项目的预期成果是一个临床可行的胆囊冷冻消融系统，具有既定的临床输送参数和剂量指南。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be the development of the first minimally invasive cryoablation solution to treat high-risk patients with gallbladder disease. The current gold standard for treating gallbladder disease is surgical removal of the gallbladder. While this procedure works well for healthy patients, the use of general anesthesia has been shown to increase complications in elderly patients with underlying chronic medical conditions, leading to a $675 million cost to the US healthcare system each year. Furthermore, patients too sick for surgery have no definitive treatment options, underscoring the need for a safer alternative. Phase I efforts demonstrated the ability to safely deliver cryoablation energy via a minimally invasive catheter system to chronically defunctionalize porcine gallbladders without removal. Phase II efforts will focus on product development of the cryoablation system and optimization of clinical delivery parameters. The goal of the technology is to allow clinicians to provide their patients with the benefits of surgery, without the risk.This Small Business Innovation Research (SBIR) Phase II project proposes to continue the development of a minimally invasive cryoablation system capable of safely and effectively targeting the gallbladder. Initial testing of the cryoablation system has demonstrated the ability to uniformly generate lethal cryoablation temperatures (-20℃) across the gallbladder lumen, leading to durable gallbladder scarring and defunctionalization in porcine animals up to 60 days post-procedure. Key technical objectives of this project are to develop the industrial design of the introducer, cryoablation catheter, and control system for improved clinical usability and manufacturability, to further test and characterize clinical delivery parameters to inform treatment planning, to improve sensor reliability and control system response time to optimize safety profile, and to validate the integrated system in vivo to demonstrate system performance with optimized dosing parameters. The system will be evaluated in an advanced benchtop model gallbladder under a thermal load, ex vivo gallbladder tissues, and an in vivo chronic animal model to optimize and validate the cryoablation catheter and integrated control system. The anticipated result of this project is a clinically viable gallbladder cryoablation system with established clinical delivery parameters and dosing guidelines.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.