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%。在GBM的治疗中出现的困难包括不能用大分子的药物来治疗。 药物渗透通过血脑屏障（BBB）;高度侵袭性GBM细胞迁移超过血脑屏障（BBB）。 实体/可见肿瘤边缘;以及大体、显微镜和遗传肿瘤内异质性。规避问题 与标准护理相关，并提高颅内电穿孔治疗的多功能性 应用中，我们的小组已经开发出一种新的肿瘤消融策略，利用双极PEF的爆发， 非热消融肿瘤。这种第二代策略被称为高频IRE（H-FIRE）， 显示局灶性组织消融，周围的BBB破坏区（BBBD）延伸数厘米 在非热损伤之外尽管在基于电穿孔的非热处理技术的发展方面取得了重大进展， 在消融治疗中，存在若干挑战和知识空白。消融/脉冲的确定 目前尚未定义终点，并且依赖于MRI和超声技术的术后成像。 因此，在母公司P01赠款的基础上，本多样性补充提案旨在进行初步的 研究H-FIRE和提出的傅立叶分析光谱法消融肿瘤组织， 在原位啮齿类动物GBM肿瘤模型中，确定脉冲终点。本项目提案有两个具体目标： 具体目标1：FAST阻抗测量的初步研究，以确定脉冲 H-FIRE消融的终点。H-FIRE疗法将应用于原位消融GBM肿瘤组织， 啮齿动物GBM肿瘤模型。已知的是，H-FIRE消融体积在一组时间之后达到饱和。 应用的突发数。因此，我们将利用新开发的傅里叶分析光谱， 电阻抗谱技术，连续监测整个H-组织阻抗的变化， 火疗具体目的2：初步研究H-FIRE与QUAD-CTX的组合疗法。 这项初步研究将阐明分子佐剂对增强H-FIRE治疗胶质瘤的作用。H- FIRE介导的血脑屏障破坏促进增强药物递送至侵袭健康脑的浸润性胶质瘤细胞 薄壁组织将采用与Aim 2相似的F98啮齿动物神经胶质瘤模型。H-FIRE疗法将是 施用和用于量化肿瘤生物发光的生物发光成像遵循独立的H- FIRE疗法和H-FIRE与新开发的QUAD-CTX的组合。

项目成果

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

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.

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

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.

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