Nonthermal Irreversible Electroporation to the Esophagus: Evaluation of Acute and Long‐Term Pathological Effects in a Rabbit Model

Background Esophageal ulceration and fistula are severe complications of pulmonary vein isolation using thermal ablation. Nonthermal irreversible electroporation (NTIRE) is a promising new technology for pulmonary vein isolation in patients with atrial fibrillation. NTIRE ablation technology has been used to treat atrial fibrillation; however, the effects of NTIRE on esophageal tissue have not been clearly described. Methods and Results A typical NTIRE electrical protocol was directly applied to esophagi in 84 New Zealand rabbits. Finite element modeling and histological analysis with 120 slices were used to analyze electric field intensity distribution and subsequent tissue changes. A parameter combination of 2000 V/cm multiplied by 90 pulses output is determined to be an effective ablation parameters combination. Within 16 weeks after ablation, no obvious lumen stenosis, epithelial erythema, erosion, ulcer, or fistula was observed in the esophageal tissue. NTIRE effectively results in esophageal cell ablation to death, and subsequently, signs of recovery gradually appear: creeping replacement and regeneration of epithelial basal cells, repair and regeneration of muscle cells, structural remodeling of the muscle layer, and finally the restoration of clear anatomical structures in all layers. Conclusions Monophasic, bipolar NTIRE delivered using plate electrodes in a novel esophageal injury model demonstrates no histopathologic changes to the esophagus at 16 weeks. Data of this study suggest that electroporation ablation is a safe modality for pulsed electroporation ablation near the esophagus.

A Study on Nonthermal Irreversible Electroporation of the Thyroid

Background: Nonthermal irreversible electroporation is a minimally invasive surgery technology that employs high and brief electric fields to ablate undesirable tissues. Nonthermal irreversible electroporation can ablate only cells while preserving intact functional properties of the extracellular structures. Therefore, nonthermal irreversible electroporation can be used to ablate tissues safely near large blood vessels, the esophagus, or nerves. This suggests that it could be used for thyroid ablation abutting the esophagus. This study examines the feasibility of using nonthermal irreversible electroporation for thyroid ablation. Methods: Rats were used to evaluate the effects of nonthermal irreversible electroporation on the thyroid. The procedure entails the delivery of high electric field pulses (1-3 kV/cm, 100 microseconds) between 2 surface electrodes bracing the thyroid. The right lobe was treated with various nonthermal irreversible electroporation pulse sequences, and the left was the control. After 24 hours of the nonthermal irreversible electroporation treatment, the thyroid was examined with hemotoxylin and eosin histological analysis. Mathematical models of electric fields and the Joule heating-induced temperature raise in the thyroid were developed to examine the experimental results. Results: Treatment with nonthermal irreversible electroporation leads to follicular cells damage, associated with cell swelling, inflammatory cell infiltration, and cell ablation. Nonthermal irreversible electroporation spares the trachea structure. Unusually high electric fields, for these types of tissue, 3000 V/cm, are needed for thyroid ablation. The mathematical model suggests that this may be related to the heterogeneous structure of the thyroid-induced distortion of local electric fields. Moreover, most of the tissue does not experience thermal damage inducing temperature elevation. However, the heterogeneous structure of the thyroid may cause local hot spots with the potential for local thermal damage. Conclusion: Nonthermal irreversible electroporation with 3000 V/cm can be used for thyroid ablation. Possible applications are treatment of hyperthyroidism and thyroid cancer. The highly heterogeneous structure of the thyroid distorts the electric fields and temperature distribution in the thyroid must be considered when designing treatment protocols for this tissue type.

Treatment of Uveal Melanoma by Nonthermal Irreversible Electroporation: Electrical and Bioheat Finite Element Model of the Human Eye

Nonthermal irreversible electroporation (NTIRE) is an new minimally invasive tissue ablation modality that uses high electric field pulses to produce irreversible permeation of the cell membrane (irreversible electroporation) while avoiding thermal damage and is applied to treat malignant tumors. This paper describes efforts to develop NTIRE as a new minimally invasive treatment modality for uveal melanoma, the most common primary intraocular malignancy in adults, and other ocular malignancies. The paper deals with a 3D mathematical simulation model of the eye that employs the simultaneous solution to the electric field equation and to the Pennes bioheat equation to predict the electric field in the eye as well as the rise in eye temperature in response to the application of a high power electric pulse. Treatment efficacy was defined as the fraction of tumor volume in which the electric field exceeded a predefined target field and treatment safety was calculated by the ratio of the electric field in the tumor to the electric field in the vitreous humor or in the macula. Results show that treatment efficacy and safety are criteria that can be used to optimize the NTIRE treatment protocol.

Nonthermal irreversible electroporation for intracranial surgical applications

Object Nonthermal irreversible electroporation (NTIRE) is a novel, minimally invasive technique to treat cancer, which is unique because of its nonthermal mechanism of tumor ablation. This paper evaluates the safety of an NTIRE procedure to lesion normal canine brain tissue. Methods The NTIRE procedure involved placing electrodes into a targeted area of brain in 3 dogs and delivering a series of short and intense electric pulses. The voltages of the pulses applied were varied between dogs. Another dog was used as a sham control. One additional dog was treated at an extreme voltage to determine the upper safety limits of the procedure. Ultrasonography was used at the time of the procedure to determine if the lesions could be visualized intraoperatively. The volumes of ablated tissue were then estimated on postprocedure MR imaging. Histological brain sections were then analyzed to evaluate the lesions produced. Results The animals tolerated the procedure with no apparent complications except for the animal that was treated at the upper voltage limit. The lesion volume appeared to decrease with decreasing voltage of applied pulses. Histological examination revealed cell death within the treated volume with a submillimeter transition zone between necrotic and normal brain. Conclusions The authors' results reveal that NTIRE at selected voltages can be safely administered in normal canine brain and that the volume of ablated tissue correlates with the voltage of the applied pulses. This preliminary study is the first step toward using NTIRE as a brain cancer treatment.