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

这一小型企业创新研究(SBIR)第一阶段项目的更广泛影响是为因全身麻醉效应而出现并发症风险较高的老年患者开发一种更安全的替代胆囊术的方法。每年大约有200,000名医疗保险患者接受手术切除他们的胆囊。不幸的是，由于全身麻醉的影响，其中24%的患者将经历围手术期并发症，美国医疗保健系统每年的总成本为5亿美元。随着人口老龄化和慢性病管理的改善，对替代胆囊手术的需求增加。该项目将开发一种影响整个胆囊面的过程(“消融”)，诱导一种愈合反应，使胆囊无能为力，不再需要切除它。这是第一项旨在通过微创方法在管内进行这一过程的技术。最终，这项技术可以被改造成为其他高表面积组织靶点创造更有效的装置。拟议的项目是对当前实践状态的消融装置的重大改进，因为它能够在闭合的管腔或器官内进行高表面积消融，例如胆囊腔。现有的传导设备是为靶向消融离散病变而设计的，而不是针对大组织靶点的治疗，如胆囊靶向。该项目的目的是开发一种新的方法，使用开放的腔内注入冷冻剂来实现组织的高表面积冷冻消融。这带来了几个独特的工程挑战，包括设计一种使制冷剂均匀分布在封闭管腔内的输送机构，以及开发一种压力管理系统，以适当地排出制冷剂气体并防止腔内压力的增加。冷冻剂分布和压力管理系统的初步优化将使用台式胆囊热负荷模型进行，以近似体内热力学。优化的设计随后将在急性和慢性动物模型中进行测试，以证明开放腔内注入制冷剂用于高表面积腔内冷冻消融胆囊术的安全性和有效性。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is to develop a safer alternative to gallbladder surgery for elderly patients at higher risks of complications due to the effects of general anesthesia. Approximately 200,000 Medicare patients undergo surgery to remove their gallbladders every year. Unfortunately, 24% of these patients will experience a perioperative complication due to the effects of general anesthesia, totaling $500 M in cost annually to the US healthcare system. As the population ages and management of chronic disease improves, the need for alternatives to gallbladder surgery increases. This project will develop a process to affect the entire surface of the gallbladder ("ablation"), inducing a healing response that will defunctionalize the gallbladder and obviate the need to remove it. This is the first technology designed to conduct this process within a tube via a minimally invasive approach. Ultimately, this technology could be adapted to create more effective devices for other high surface area tissue targets.The proposed project is a significant improvement over current state-of-practice ablation devices due to its ability to deliver high-surface area ablation within a closed lumen or organ, such as the gallbladder. Existing conductive devices are designed for targeted ablation of discrete lesions rather than therapeutic delivery to large tissue targets, such as the gallbladder. The aim of this project is to develop a new process using open lumen instillation of cryogen to achieve high surface area cryoablation of tissues. This raises several unique engineering challenges, including the design of a delivery mechanism for the uniform distribution of cryogen across a closed lumen and development of a pressure management system to properly evacuate the cryogen gas and prevent an increase in intraluminal pressure. Initial optimization of the cryogen distribution and pressure management system will be conducted using a benchtop thermal load model of the gallbladder to approximate the in vivo thermodynamics. Optimized designs will then be tested in acute and chronic animal models to demonstrate the safety and efficacy of open lumen instillation of cryogen for high surface area intraluminal cryoablation of the gallbladder.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.