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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要综合时间纳秒脉冲不可逆的电穿孔（INSPIRE）是一种微创的治疗方法无法手术的实体瘤。该处理使用超短电脉冲来破坏细胞膜，并在明确的体积内诱导坏死和凋亡细胞死亡的可调组合。该疗法是通过将一个或多个电极引入肿瘤，然后将一系列500NS引入2000NS 电极和外部接地垫之间的电脉冲。为了治疗肿瘤发生在我们周围的临界结构附近，利用主动温度反馈来限制焦耳加热并防止有害热损伤。利用离体，体内和计算结果的组合，我们假设 Inspire将是使用单个的绝大多数无法使用的肿瘤的安全有效治疗当涂抹器方法和兼容的脉冲发生器能够高压输出时能够高压输出控制可防止靶向脱靶热损伤。该建议将利用最新的发展电压电力电子设备开发能够安全管理的新仪器体内治疗。这些治疗方法的安全性，功效和可重复性将组合评估体外，体内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者设计。这项研究将通过体内研究表明这些治疗对犬兽医患者自发肝肿瘤的安全性和功效。