Development of an INSPIRE System for the Treatment of Inoperable Liver Tumors

项目摘要 积分时间纳秒脉冲不可逆电穿孔(INSPIRE)是一种微创治疗 无法手术的实体肿瘤。这种治疗方法使用超短电脉冲来破坏细胞膜的稳定，并 在明确的体积内诱导可调节的坏死性和凋亡性细胞死亡。治疗方法是 通过将一个或多个电极引入肿瘤中，然后提供一系列500 ns到2000 ns的信号来实施 电极和外部接地垫之间的电脉冲。使肿瘤的治疗成为可能 发生在我们周围的关键结构附近，利用主动温度反馈来限制焦耳发热并防止 有害的热损伤。结合体外、体内和计算结果，我们假设 INSPIRE将是一种安全有效的治疗绝大多数无法手术的肿瘤的方法 施加器方法和在激活温度时能够高电压输出的兼容脉冲发生器 控制被用来防止目标外的热损伤。这项建议将利用最新的发展在高 电压电力电子公司开发能够安全管理这些设备的新仪器 活体内的治疗。这些治疗的安全性、有效性和可重复性将综合评估。 体外、体外和体内模型以及在这些研究中产生的数据将被用于优化治疗 规划算法和临床应用设计。这项研究将以一项活体研究证明 这些治疗方法对犬类兽医患者自发性肝肿瘤的安全性和有效性。

Project Summary Integrated time nanosecond pulse irreversible electroporation (INSPIRE) is a minimally invasive treatment for inoperable solid tumors. This treatment uses ultrashort electrical pulses to destabilize the cell membrane and induce a tunable combination of necrotic and apoptotic cell death within a well-defined volume. The therapy is implemented by introducing one or more electrodes into the tumor then delivering a series of 500ns to 2000ns electrical pulses between an electrode and an external grounding pad. To enable treatment of tumors which occur near our around critical structures active temperature feedback is utilized to limit Joule heating and prevent deleterious thermal injury. Using a combination of ex vivo, in vivo, and computational results we hypothesize that INSPIRE will be a safe and effective treatment for the vast majority of inoperable tumors utilizing a single applicator approach and a compatible pulse generator capable of high voltage outputs when active temperature control is utilized to prevent off-target thermal injury. This proposal will leverage recent developments in high voltage power electronics to develop new instrumentation which is capable of safely administering these treatments in vivo. The safety, efficacy, and reproducibility of these treatments will be evaluated in a combination of in vitro, ex vivo, and in vivo models and the data generated in these studies will be utilized to optimize treatment planning algorithms and clinical applicators designs. The study will culminate with an in vivo study demonstrating the safety and efficacy of these treatments against spontaneous liver tumors in canine veterinary patients.