Rapid Electrical Impedance Spectroscopy for Detection of High-Frequency Irreversible Electroporation Ablation Growth in a Rodent Glioma Model

快速电阻抗光谱法检测啮齿动物神经胶质瘤模型中高频不可逆电穿孔消融生长

• 批准号: 10310562
• 负责人: Waldemar Debinski
• 金额: $ 14.18万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-17 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10310562
• 关键词: Ablation; Address; Adjuvant; American; Bioluminescence; Blood - brain barrier anatomy; Brain Neoplasms; Bypass; Canis familiaris; Cardiac; Catheters; Cell Death; Cell Nucleus; Cell membrane; Cells; Cerebrum; Complex; Convection; Cyclophosphamide; Defect; Detection; Development; Diagnosis; Diffusion; Drug Delivery Systems; Electrodes; Electroporation; Electroporation Therapy; Excision; Exposure to; Focused Ultrasound; Fourier Analysis; Frequencies; General Anesthesia; Generations; Genetic; Glioblastoma; Glioma; Grant; Growth; Hepatic; Heterogeneity; Hour; Image; Infusion procedures; Invaded; Investigation; Karnofsky Performance Status; Kidney; Knowledge; Lesion; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Measurement; Mediating; Microbubbles; Microscopic; Modality; Modeling; Molecular; Monitor; Muscle; Muscle Contraction; Necrosis; Needles; Nerve; Pancreas; Paralysed; Parents; Patients; Performance; Pharmaceutical Preparations; Physiologic pulse; Pilot Projects; Postoperative Period; Prognosis; Prostate; Proteins; Radiation; Recovery; Reflux; Reproducibility; Rodent; Solid; Solid Neoplasm; Spectrum Analysis; Survival Rate; Techniques; Technology; Therapeutic; Tissues; Tumor Tissue; Ultrasonography; base; blood-brain barrier disruption; blood-brain barrier permeabilization; brain parenchyma; cancer cell; chemotherapy; clinically relevant; combinatorial; electric field; electric impedance; improved; migration; nanoparticle; nanoscale; neoplastic; novel; occludin; parent grant; preclinical study; pressure; standard of care; temozolomide; treatment strategy; tumor; tumor ablation; tumor heterogeneity; voltage

Diversity Supplement Project Summary The most common and aggressive malignant brain tumor, glioblastoma multiforme (GBM), demonstrates a 5- year survival rate of only 5.6%. Difficulties arising in the treatment of GBM include the inability of large molecular agents to permeate through the blood-brain barrier (BBB); migration of highly invasive GBM cells beyond the solid/visible tumor margin; and gross, microscopic, and genetic intratumor heterogeneity. To circumvent issues associated with standard of care and to improve the versatility of electroporation-based therapies for intracranial applications, our group has developed a novel tumor ablation strategy which utilizes bursts of bipolar PEFs to nonthermally ablate tumors. This second-generation strategy, termed high-frequency IRE (H-FIRE), demonstrates focal tissue ablation with a surrounding zone of BBB disruption (BBBD) that extends centimeters beyond the nonthermal lesion. Despite major progress in development of electroporation-based nonthermal ablation therapies, several challenges and gaps in knowledge exist. The determination of an ablation/pulsing endpoint is not currently defined and is reliant on postoperative imaging with MRI and ultrasound techniques. Therefore, building off the parent P01 grant, this Diversity Supplement proposal seeks to conduct a preliminary investigation of H-FIRE and the proposed Fourier Analysis SpecTroscopy to ablate neoplastic tissue in an orthotopic rodent GBM tumor model and determine a pulsing endpoint. This project proposal has 2 specific aims: Specific Aim 1: Preliminary investigation of FAST impedance measurements to determine a pulsing endpoint for H-FIRE ablation. H-FIRE therapy will be applied to ablate GBM tumor tissue in an orthotopic rodent GBM tumor model. It is known that the H-FIRE ablation volume reaches a saturation following a set number of bursts applied. Therefore, we will utilize the newly developed Fourier Analysis SpecTroscopy, a rapid electrical impedance spectroscopy technique, to continually monitor changes in tissue impedance throughout H- FIRE therapy. Specific Aim 2: Preliminary investigation of combinatorial H-FIRE therapy with QUAD-CTX. This pilot study will elucidate the effects of a molecular adjuvant to enhance glioma treatment with H-FIRE. H- FIRE-mediated BBB disruption facilitates enhanced drug delivery to infiltrative glioma cells invading healthy brain parenchyma. An F98 rodent glioma model, similar to that of Aim 2, will be employed. H-FIRE therapy will be administered and bioluminescent imaging used to quantify the tumor bioluminescence follow stand-alone H- FIRE therapy and combinatorial H-FIRE with newly developed QUAD-CTX.

多样性补充项目摘要 最常见和最具侵袭性的恶性脑肿瘤，多形性胶质母细胞瘤 (GBM)，表现出 5- 年生存率仅为5.6%。 GBM 治疗中出现的困难包括大分子不能 药物可透过血脑屏障（BBB）；高度侵袭性 GBM 细胞迁移至细胞外 实性/可见肿瘤边缘；以及肿瘤内的总体、微观和遗传异质性。规避问题 与护理标准相关并提高基于电穿孔的颅内治疗的多功能性 我们的团队开发了一种新型肿瘤消融策略，利用双极 PEF 的爆​​发来 非热消融肿瘤。这种第二代策略称为高频 IRE (H-FIRE)， 演示局灶性组织消融，周围 BBB 破坏区 (BBBD) 延伸数厘米 超出非热损伤。尽管基于电穿孔的非热技术的发展取得了重大进展 消融疗法存在一些挑战和知识差距。消融/脉冲的确定 目前尚未定义终点，并且依赖于术后 MRI 和超声技术成像。 因此，在母公司 P01 拨款的基础上，本多样性补充提案旨在进行初步 H-FIRE 的研究和拟议的傅里叶分析光谱法用于消融肿瘤组织 原位啮齿动物​​ GBM 肿瘤模型并确定脉冲终点。该项目提案有 2 个具体目标： 具体目标 1：初步研究 FAST 阻抗测量以确定脉冲 H-FIRE 消融的终点。 H-FIRE 疗法将用于在原位消融 GBM 肿瘤组织 啮齿动物GBM肿瘤模型。众所周知，H-FIRE 消融体积在经过一组后达到饱和。 应用的突发数量。因此，我们将利用新开发的傅里叶分析光谱仪，一种快速的 电阻抗光谱技术，持续监测整个 H- 组织阻抗的变化 火疗。具体目标 2：H-FIRE 与 QUAD-CTX 组合疗法的初步研究。 这项初步研究将阐明分子佐剂对增强 H-FIRE 神经胶质瘤治疗的作用。 H- FIRE介导的BBB破坏有助于增强药物向侵入健康大脑的浸润性神经胶质瘤细胞的输送 薄壁组织。将使用与 Aim 2 类似的 F98 啮齿动物神经胶质瘤模型。 H-FIRE 疗法将 用于量化肿瘤生物发光的生物发光成像遵循独立的 H- FIRE 疗法以及 H-FIRE 与新开发的 QUAD-CTX 的组合。

项目成果

Influence of Pulsed Electric Fields and Mitochondria-Cytoskeleton Interactions on Cell Respiration.

脉冲电场和线粒体-细胞骨架相互作用对细胞呼吸的影响。

• 发表时间: 2018-06-19
• 影响因子: 3.4
• 作者: Goswami, Ishan;Perry, Justin B;Allen, Mitchell E;Brown, David A;von Spakovsky, Michael R;Verbridge, Scott S
• 通讯作者: Verbridge, Scott S

Temporal Characterization of Blood-Brain Barrier Disruption with High-Frequency Electroporation.

高频电穿孔血脑屏障破坏的时间特征。

• 发表时间: 2019-11-23
• 影响因子: 5.2
• 作者: Lorenzo, Melvin F;Thomas, Sean C;Kani, Yukitaka;Hinckley, Jonathan;Lee, Matthew;Adler, Joy;Verbridge, Scott S;Hsu, Fang;Robertson, John L;Davalos, Rafael V;Rossmeisl Jr, John H
• 通讯作者: Rossmeisl Jr, John H

Cytoskeletal Disruption after Electroporation and Its Significance to Pulsed Electric Field Therapies.

电穿孔后细胞骨架的破坏及其对脉冲电场治疗的意义。

• 发表时间: 2020-04-30
• 影响因子: 5.2
• 作者: Graybill, Philip M;Davalos, Rafael V
• 通讯作者: Davalos, Rafael V

Comparison of direct measurement of intracranial pressures and presumptive clinical and magnetic resonance imaging indicators of intracranial hypertension in dogs with brain tumors.

脑肿瘤犬颅内压直接测量与颅内高压推定临床和磁共振成像指标的比较。

• 发表时间: 2020-07
• 影响因子: 2.6
• 作者: Giannasi, Savannah;Kani, Yukitaka;Hsu, Fang;Rossmeisl, John H
• 通讯作者: Rossmeisl, John H

A Multiplexed Microfluidic Device to Measure Blood-Brain Barrier Disruption by Pulsed Electric Fields.

一种通过脉冲电场测量血脑屏障破坏的多重微流体装置。

• 发表时间: 2021-11
• 作者: Graybill, Philip M;Davalos, Rafael V
• 通讯作者: Davalos, Rafael V