High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction

Arena, Christopher B.; Sano, Michael B.; Rossmeisl, John H.; Caldwell, John L.; García, Paulo A.; Rylander, Marissa Nichole; Davalos, Rafael V.

doi:10.1186/1475-925x-10-102

Cited by 273 publications

(203 citation statements)

References 51 publications

Supporting

Mentioning

198

Contrasting

Unclassified

Order By: Relevance

“…S10 and S11). It has been previously observed that H-FIRE treatment generates more homogenous lesions (2,24,(27)(28)(29)(30)(31) and in this article, we offer an explanation for that phenomenon.…”

Section: Figurementioning

confidence: 52%

Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation

Murovec

Sweeney

Latouche

et al. 2016

Biophysical Journal

View full text Add to dashboard Cite

Many approaches for studying the transmembrane potential (TMP) induced during the treatment of biological cells with pulsed electric fields have been reported. From the simple analytical models to more complex numerical models requiring significant computational resources, a gamut of methods have been used to recapitulate multicellular environments in silico. Cells have been modeled as simple shapes in two dimensions as well as more complex geometries attempting to replicate realistic cell shapes. In this study, we describe a method for extracting realistic cell morphologies from fluorescence microscopy images to generate the piecewise continuous mesh used to develop a finite element model in two dimensions. The preelectroporation TMP induced in tightly packed cells is analyzed for two sets of pulse parameters inspired by clinical irreversible electroporation treatments. We show that high-frequency bipolar pulse trains are better, and more homogeneously raise the TMP of tightly packed cells to a simulated electroporation threshold than conventional irreversible electroporation pulse trains, at the expense of larger applied potentials. Our results demonstrate the viability of our method and emphasize the importance of considering multicellular effects in the numerical models used for studying the response of biological tissues exposed to electric fields.

show abstract

Section: Figurementioning

confidence: 52%

Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation

Murovec

Sweeney

Latouche

et al. 2016

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…This is an important distinction, as IRE requires the administration of general anesthesia and paralytic agents in order to eliminate muscle contractions [9].…”

Section: Discussionmentioning

confidence: 99%

Electrical Membrane Breakdown (EMB): Preliminary Findings of a New Method of Non-thermal Tissue Ablation

Gm¹,

Dg²,

Ja³

et al. 2017

J Clin Exp Pathol

View full text Add to dashboard Cite

Electrical membrane breakdown (EMB) is a novel form of non-thermal treatment that has not, to our knowledge, been previously evaluated for its potential utility as an ablation mechanism. The findings with EMB immediately after treatment were compared with other forms of ablation (cryoablation and IRE (irreversible electroporation)) in the porcine liver clinically, ultrasonographically, and by light microscopy and ultrastructural analysis. Clinically, EMB did not induce muscular contractions, in contrast with IRE. By ultrasound, all lesions were hypoechoic when compared to the untreated liver. EMB created a consistent pattern of immediate tissue destruction at the light microscopic and ultrastructural level, characterized by pulse-dose-related coagulative necrosis and nuclear pyknosis, preserved blood vessels and adjacent structures, and sharply demarcated margins. We conclude that the profile of EMB ablation is distinctive and unique, inducing necrosis by immediate electrical rupture of cell membranes non-thermally while preserving proteins and adjacent vessels with potentially superior stimulation of the immune system than other ablation modalities.

show abstract

“…We have developed a novel technology, coined high-frequency irreversible electroporation (H-FIRE) that represents a significant advancement in IRE therapy, the specifics of which have been covered in Part III of this chapter (80). Briefly, the treatment of patients with high-amplitude IRE pulses (1-3 kv, ~100 µs) requires administration of neuroparalytic agents in order to abolish muscle contractions associated with pulse delivery (79).…”

Section: Irreversible Electroporationmentioning

confidence: 99%

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part V: Clinically Relevant Model for Testing New Therapeutic Approaches

Rossmeisl

2017

Glioblastoma

View full text Add to dashboard Cite

A significant obstacle to the development of new brain tumor therapeutics remains the lack of rodent models that faithfully reproduce the in vivo complexities of human glioblastoma. Dogs and humans are the only species that frequently develop spontaneous brain tumors. Remarkable clinical, phenotypic, and molecular similarities exist between human and canine malignant glioma. Our research has focused on the development of pharmacologically tractable molecular targets common to human and canine gliomas, as well as the discovery Canine Brain Tumor Models 406 and refinement of novel methods of drug delivery to the brain, such as convection-enhanced delivery (CED), irreversible electroporation (IRE), and focused ultrasound, that can overcome the limitations imposed by the bloodbrain and blood-tumor barriers. Through the conduct of early phase clinical trials in dogs, we demonstrate the safety, feasibility, and preliminary efficacies of IL-13RA2-and EphA2-targeted bacterial cytotoxins and IRE for the treatment of spontaneous malignant glioma, illustrate the clinical utility of real-time imaging monitored CED as a robust drug delivery platform, and describe the use of the tumor-bearing dog in transcranial-focused ultrasound applications related to neuro-oncology. The dog brain cancer model offers unique opportunities to expedite the clinical translation of cancer therapeutics through the design of preclinical investigations that ask and answer drug and medical device development questions that cannot be sufficiently addressed in rodent models.

show abstract

High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction

Cited by 273 publications

References 51 publications

Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation

Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation

Electrical Membrane Breakdown (EMB): Preliminary Findings of a New Method of Non-thermal Tissue Ablation

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part V: Clinically Relevant Model for Testing New Therapeutic Approaches

Contact Info

Product

Resources

About