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 最常见和侵略性的恶性脑肿瘤多形胶质母细胞瘤（GBM）表现出5-- 年生存率仅为5.6％。在GBM治疗中产生的困难包括大分子的无法 通过血脑屏障（BBB）渗透的代理；高度侵入性的GBM细胞的迁移 固体/可见的肿瘤边缘；和毛，微观和遗传肿瘤内异质性。避免问题 与护理标准相关，并改善基于电穿孔的疗法的多功能性 应用程序，我们的小组开发了一种新型的肿瘤消融策略，该策略利用双极PEF爆发到 非热烧制肿瘤。这种第二代策略称为高频IRE（H-Fire）， 展示了局灶性组织消融，其周围的BBB破坏区域（BBBD）扩展了厘米 超越非热病变。尽管基于电穿孔的非热的发展取得了重大进展 消融疗法，知识中存在一些挑战和差距。消融/脉冲的确定 端点目前尚未定义，并且依赖于MRI和超声技术的术后成像。 因此，建立父母P01赠款，该多样性补充提案旨在进行初步 研究H火和提出的傅里叶分析光谱学对灌溉肿瘤组织的研究 原位啮齿动物​​GBM肿瘤模型并确定脉冲终点。该项目提案具有2个具体目标： 特定目标1：快速阻抗测量以确定脉冲的初步研究 H火消融的终点。 H火路疗法将应用于原位的消融GBM肿瘤组织 啮齿动物GBM肿瘤模型。众所周知，H-fire消融体积在集合之后达到饱和度 施加爆发数。因此，我们将利用新开发的傅立叶分析光谱，快速 电阻抗光谱技术，以不断监视整个H-的组织阻抗的变化 消防疗法。特定目的2：对QUAD-CTX组合H-FIRE疗法的初步研究。 这项初步研究将阐明分子佐剂对使用H火的神经胶质瘤治疗的影响。 h- 消防介导的BBB破坏促进了侵入健康大脑的浸润性神经胶质瘤细胞的增强的药物 实质。将采用类似于AIM 2的F98啮齿动物神经瘤模型。 H火路疗法将是 用于量化肿瘤发光的施用和生物发光成像遵循独立的H- 消防疗法和新开发的Quad-CTX的H-fire组合。

项目成果

Characterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporation

• DOI: 10.34133/2019/8081315
• 发表时间: 2019-01-01
• 期刊: RESEARCH
• 影响因子: 11
• 作者: Ivey, J. W.;Wasson, E. M.;Verbridge, S. S.
• 通讯作者: Verbridge, S. S.

Controlled Catheter Movement Affects Dye Dispersal Volume in Agarose Gel Brain Phantoms.

受控导管运动影响琼脂糖凝胶脑模型中的染料分散量。

• DOI: 10.3390/pharmaceutics12080753
• 发表时间: 2020
• 期刊: Pharmaceutics
• 影响因子: 5.4
• 作者: Mehta,JasonN;McRoberts,GabrielleR;Rylander,ChristopherG
• 通讯作者: Rylander,ChristopherG

Biocompatibility of the fiberoptic microneedle device chronically implanted in the rat brain.

• DOI: 10.1016/j.rvsc.2021.12.018
• 发表时间: 2022-03
• 期刊: Research in veterinary science
• 影响因子: 2.4
• 作者: Kani Y;Hinckley J;Robertson JL;Mehta JM;Rylander CG;Rossmeisl JH
• 通讯作者: Rossmeisl JH

Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation.

• DOI: 10.1038/s41598-021-87228-5
• 发表时间: 2021-04-07
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Hendricks-Wenger A;Aycock KN;Nagai-Singer MA;Coutermarsh-Ott S;Lorenzo MF;Gannon J;Uh K;Farrell K;Beitel-White N;Brock RM;Simon A;Morrison HA;Tuohy J;Clark-Deener S;Vlaisavljevich E;Davalos RV;Lee K;Allen IC
• 通讯作者: Allen IC

High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas.

• DOI: 10.3389/fonc.2023.1171278
• 发表时间: 2023
• 期刊: FRONTIERS IN ONCOLOGY
• 影响因子: 4.7
• 作者: Campelo, Sabrina N.;Lorenzo, Melvin F.;Partridge, Brittanie;Alinezhadbalalami, Nastaran;Kani, Yukitaka;Garcia, Josefa;Saunier, Sofie;Thomas, Sean C.;Hinckley, Jonathan;Verbridge, Scott S.;Davalos, Rafael V.;Rossmeisl Jr, John H. H.
• 通讯作者: Rossmeisl Jr, John H. H.