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

开发用于治疗无法手术的肝脏肿瘤的 INSPIRE 系统

• 批准号: 10560677
• 负责人: Michael Benjamin Sano
• 金额: $ 58.91万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-14 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10560677
• 关键词: Ablation; Abscopal effect; Admission activity; Affect; Aftercare; Algorithms; Animal Disease Models; Animal Model; Animals; Antitumor Response; Apoptotic; Applications Grants; Biological; Biological Assay; Biomedical Engineering; Biophysics; Blood Vessels; Blood specimen; Canis familiaris; Cell Death; Cell membrane; Cells; Charge; Clinical; Coagulative necrosis; Complex; Dangerousness; Data; Development; Diagnosis; Disease; Dose; Electrodes; Electronics; Electroporation; Electroporation Therapy; Feedback; Fine needle aspiration biopsy; Fire - disasters; Flow Cytometry; Generations; Genomics; Goals; Heating; Heterogeneity; Histologic; In Vitro; Inflammatory; Life; Liver; Liver neoplasms; Malignant Neoplasms; Malignant neoplasm of liver; Membrane; Modality; Modeling; Morphology; Necrosis; Normal Cell; Organ; Outcome; Output; Patients; Physiologic pulse; Physiological; Primary Neoplasm; Primary carcinoma of the liver cells; Production; Prognosis; Protocols documentation; Public Health; Radiation therapy; Recurrence; Reproducibility; Research Project Grants; Resectable; Resected; Safety; Series; Shapes; Solid; Solid Neoplasm; Source; Structure; System; Temperature; Testing; Time; Tissues; Toxic effect; Treatment Efficacy; Treatment Protocols; Treatment outcome; Unresectable; X-Ray Computed Tomography; adaptive immune response; anti-cancer; aspirate; cancer cell; cancer therapy; chemotherapy; cohort; design; effective therapy; electrical property; experimental study; follow-up; heat injury; in vivo; in vivo Model; instrumentation; lymph nodes; mechanical properties; migration; minimally invasive; mortality; nanosecond; neoplastic cell; novel; optimal treatments; peripheral blood; pre-clinical; preclinical evaluation; preservation; prevent; safety assessment; sensor; survival outcome; therapy design; therapy outcome; treatment optimization; treatment planning; tumor; tumor ablation; tumor growth; voltage

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.

项目概要 集成时间纳秒脉冲不可逆电穿孔 (INSPIRE) 是一种微创治疗方法 无法手术的实体瘤。这种治疗使用超短电脉冲来破坏细胞膜的稳定性， 在明确的体积内诱导坏死和凋亡细胞死亡的可调节组合。治疗方法是 通过将一个或多个电极引入肿瘤然后提供一系列 500ns 至 2000ns 的时间来实现 电极和外部接地垫之间的电脉冲。为了能够治疗肿瘤 发生在我们周围的关键结构附近，利用主动温度反馈来限制焦耳热并防止 有害的热损伤。结合离体、体内和计算结果，我们假设 INSPIRE 将是一种安全有效的治疗方法，可利用单一药物治疗绝大多数无法手术的肿瘤。 涂抹器方法和兼容的脉冲发生器能够在活跃温度下输出高电压 利用控制来防止脱靶热损伤。该提案将利用高技术领域的最新发展 电压电力电子设备开发能够安全管理这些的新仪器 体内治疗。这些治疗的安全性、有效性和可重复性将综合评估 体外、离体和体内模型以及这些研究中生成的数据将用于优化治疗 规划算法和临床施药器设计。该研究将以体内研究证明 这些疗法针对犬类兽医患者自发性肝肿瘤的安全性和有效性。