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

项目摘要 集成时间纳秒脉冲不可逆电穿孔（INSPIRE）是一种微创治疗方法， 不能手术的实体瘤这种治疗使用超短电脉冲来使细胞膜不稳定， 在明确限定体积内诱导坏死和凋亡细胞死亡的可调组合。所述疗法是 通过将一个或多个电极引入肿瘤中，然后递送一系列500 ns至2000 ns的脉冲来实现 电极和外部接地垫之间的电脉冲。为了能够治疗肿瘤， 发生在我们周围的临界结构附近，主动温度反馈用于限制焦耳加热并防止 有害的热损伤。使用体外、体内和计算结果的组合，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， 施加器的方法和兼容的脉冲发生器能够高电压输出时，主动温度 利用控制来防止偏离目标的热损伤。该提案将利用最近的发展， 电压电力电子开发新的仪器，能够安全地管理这些 体内治疗。这些治疗的安全性、有效性和可重复性将在一个组合中进行评估。 体外、离体和体内模型以及这些研究中产生的数据将用于优化治疗 规划算法和临床施用器设计。该研究将以体内研究结束， 这些治疗对犬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.