Principles of Tissue Engineering With Nonthermal Irreversible Electroporation

2010 ◽  
Vol 133 (1) ◽  
Author(s):  
Mary Phillips ◽  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Electric Fields ◽  
Irreversible Electroporation ◽  
Membrane Lipid ◽  
Element Analysis ◽  
Tissue Scaffold ◽  
Invasive Approach ◽  
Electric Pulses ◽  
Thermal Fields ◽  
Nonthermal Irreversible Electroporation ◽  
Electric Parameters

Nonthermal irreversible electroporation (NTIRE) is an emerging tissue ablation modality that may be ideally suited in developing a decellularized tissue graft. NTIRE utilizes short electric pulses that produce nanoscale defects in the cell membrane lipid bilayer. The electric parameters can be chosen in such a way that Joule heating to the tissue is minimized and cell death occurs solely due to loss in cell homeostasis. By coupling NTIRE with the body’s response, the cells can be selectively ablated and removed, leaving behind a tissue scaffold. Here, we introduce two different methods for developing a decellularized arterial scaffold. The first uses an electrode clamp that is applied to the outside of a rodent carotid artery and the second applies an endovascular minimally invasive approach to apply electric fields from the inner surface of the blood vessels. Both methods are first modeled using a transient finite element analysis of electric and thermal fields to ensure that the electric parameters used in this study will result in minimal thermal damage. Experimental work demonstrates that both techniques result in not only a decellularized arterial construct but an endothelial regrowth is evident along the lumen 7 days after treatment, indicating that the extracellular matrix was not damaged by electric and thermal fields and is still able to support cell growth.

scholarly journals A Study on Nonthermal Irreversible Electroporation of the Thyroid

2019 ◽  
Vol 18 ◽  
pp. 153303381987630
Author(s):  
Yanpeng Lv ◽  
Yanfang Zhang ◽  
Jianwei Huang ◽  
Yunlong Wang ◽  
Boris Rubinsky
Keyword(s):  
Electric Fields ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Pulse Sequences ◽  
Cell Swelling ◽  
Tissue Type ◽  
Heterogeneous Structure ◽  
Treatment Protocols ◽  
Thyroid Ablation ◽  
Nonthermal Irreversible Electroporation

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.

Endovascular Nonthermal Irreversible Electroporation: A Finite Element Analysis

2010 ◽  
Vol 132 (3) ◽  
Author(s):  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Finite Element ◽  
Electric Field ◽  
Electric Fields ◽  
Joule Heating ◽  
Arterial Wall ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Phospholipid Bilayer ◽  
Tissue Ablation ◽  
Nonthermal Irreversible Electroporation

Tissue ablation finds an increasing use in modern medicine. Nonthermal irreversible electroporation (NTIRE) is a biophysical phenomenon and an emerging novel tissue ablation modality, in which electric fields are applied in a pulsed mode to produce nanoscale defects to the cell membrane phospholipid bilayer, in such a way that Joule heating is minimized and thermal damage to other molecules in the treated volume is reduced while the cells die. Here we present a two-dimensional transient finite element model to simulate the electric field and thermal damage to the arterial wall due to an endovascular NTIRE novel device. The electric field was used to calculate the Joule heating effect, and a transient solution of the temperature is presented using the Pennes bioheat equation. This is followed by a kinetic model of the thermal damage based on the Arrhenius formulation and calculation of the Henriques and Moritz thermal damage integral. The analysis shows that the endovascular application of 90, 100 μs pulses with a potential difference of 600 V can induce electric fields of 1000 V/cm and above across the entire arterial wall, which are sufficient for irreversible electroporation. The temperature in the arterial wall reached a maximum of 66.7°C with a pulse frequency of 4 Hz. Thermal damage integral showed that this protocol will thermally damage less than 2% of the molecules around the electrodes. In conclusion, endovascular NTIRE is possible. Our study sets the theoretical basis for further preclinical and clinical trials with endovascular NTIRE.

scholarly journals Nonthermal irreversible electroporation for intracranial surgical applications

2011 ◽  
Vol 114 (3) ◽  
pp. 681-688 ◽  
Author(s):  
Thomas L. Ellis ◽  
Paulo A. Garcia ◽  
John H. Rossmeisl ◽  
Natalia Henao-Guerrero ◽  
John Robertson ◽  
...  
Keyword(s):  
Irreversible Electroporation ◽  
Invasive Technique ◽  
Normal Brain ◽  
Lesion Volume ◽  
Sham Control ◽  
Electric Pulses ◽  
Canine Brain ◽  
Nonthermal Irreversible Electroporation ◽  
Preliminary Study ◽  
Voltage Limit

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.

The Effect of Small Intestine Heterogeneity on Irreversible Electroporation Treatment Planning

2014 ◽  
Vol 136 (9) ◽  
Author(s):  
Mary Phillips
Keyword(s):  
Finite Element ◽  
Small Intestine ◽  
Electric Field ◽  
Treatment Planning ◽  
Electric Fields ◽  
Irreversible Electroporation ◽  
Experimental Results ◽  
Heterogeneous Structure ◽  
Element Analysis

Nonthermal irreversible electroporation (NTIRE) is an ablation modality that utilizes microsecond electric fields to produce nanoscale defects in the cell membrane. This results in selective cell death while preserving all other molecules, including the extracellular matrix. Here, finite element analysis and experimental results are utilized to examine the effect of NTIRE on the small intestine due to concern over collateral damage to this organ during NTIRE treatment of abdominal cancers. During previous studies, the electrical treatment parameters were chosen based on a simplified homogeneous tissue model. The small intestine, however, has very distinct layers, and a more realistic model is needed to further develop this technology for precise clinical applications. This study uses a two-dimensional finite element solution of the Laplace and heat conduction equations to investigate how small intestine heterogeneities affect the electric field and temperature distribution. Experimental results obtained by applying NTIRE to the rat small intestine in vivo support the heterogeneous effect of NTIRE on the tissue. The numerical modeling indicates that the electroporation parameters chosen for this study avoid thermal damage to the tissue. This is supported by histology obtained from the in vivo study, which showed preservation of extracellular structures. The finite element model also indicates that the heterogeneous structure of the small intestine has a significant effect on the electric field and volume of cell ablation during electroporation and could have a large impact on the extent of treatment. The heterogeneous nature of the tissue should be accounted for in clinical treatment planning.

scholarly journals The use of high-frequency short bipolar pulses in cisplatin electrochemotherapy in vitro

2019 ◽  
Vol 53 (2) ◽  
pp. 194-205 ◽  
Author(s):  
Maria Scuderi ◽  
Matej Rebersek ◽  
Damijan Miklavcic ◽  
Janja Dermol-Cerne
Keyword(s):  
Electric Fields ◽  
High Frequency ◽  
Irreversible Electroporation ◽  
Mouse Skin ◽  
Heart Rhythm ◽  
Muscle Contractions ◽  
Skin Melanoma ◽  
Negative Pulse ◽  
Electric Pulses

Abstract Background In electrochemotherapy (ECT), chemotherapeutics are first administered, followed by short 100 μs monopolar pulses. However, these pulses cause pain and muscle contractions. It is thus necessary to administer muscle relaxants, general anesthesia and synchronize pulses with the heart rhythm of the patient, which makes the treatment more complex. It was suggested in ablation with irreversible electroporation, that bursts of short high-frequency bipolar pulses could alleviate these problems. Therefore, we designed our study to verify if it is possible to use high-frequency bipolar pulses (HF-EP pulses) in electrochemotherapy. Materials and methods We performed in vitro experiments on mouse skin melanoma (B16-F1) cells by adding 1–330 μM cisplatin and delivering either (a) eight 100 μs long monopolar pulses, 0.4–1.2 kV/cm, 1 Hz (ECT pulses) or (b) eight bursts at 1 Hz, consisting of 50 bipolar pulses. One bipolar pulse consisted of a series of 1 μs long positive and 1 μs long negative pulse (0.5–5 kV/cm) with a 1 μs delay in-between. Results With both types of pulses, the combination of electric pulses and cisplatin was more efficient in killing cells than cisplatin or electric pulses only. However, we needed to apply a higher electric field in HF-EP (3 kV/cm) than in ECT (1.2 kV/cm) to obtain comparable cytotoxicity. Conclusions It is possible to use HF-EP in electrochemotherapy; however, at the expense of applying higher electric fields than in classical ECT. The results obtained, nevertheless, offer an evidence that HF-EP could be used in electrochemotherapy with potentially alleviated muscle contractions and pain.

Nonthermal Irreversible Electroporation for Tissue Decellularization

2010 ◽  
Vol 132 (9) ◽  
Author(s):  
Mary Phillips ◽  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Electrical Parameters ◽  
Irreversible Damage ◽  
Tissue Scaffold ◽  
Electrical Fields ◽  
Nonthermal Irreversible Electroporation ◽  
Tissue Scaffolding ◽  
Living Tissues

Tissue scaffolding is a key component for tissue engineering, and the extracellular matrix (ECM) is nature’s ideal scaffold material. A conceptually different method is reported here for producing tissue scaffolds by decellularization of living tissues using nonthermal irreversible electroporation (NTIRE) pulsed electrical fields to cause nanoscale irreversible damage to the cell membrane in the targeted tissue while sparing the ECM and utilizing the body’s host response for decellularization. This study demonstrates that the method preserves the native tissue ECM and produces a scaffold that is functional and facilitates recellularization. A two-dimensional transient finite element solution of the Laplace and heat conduction equations was used to ensure that the electrical parameters used would not cause any thermal damage to the tissue scaffold. By performing NTIRE in vivo on the carotid artery, it is shown that in 3 days post NTIRE the immune system decellularizes the irreversible electroporated tissue and leaves behind a functional scaffold. In 7 days, there is evidence of endothelial regrowth, indicating that the artery scaffold maintained its function throughout the procedure and normal recellularization is taking place.

Irreversible Electroporation: Expanding the Armamentarium against Pancreatic Cancer

2019 ◽  
Vol 03 (02) ◽  
pp. 138-142
Author(s):  
Gray R. Lyons ◽  
Brian J. Schiro ◽  
Govindarajan Narayanan
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Treatment Algorithm ◽  
Advanced Pancreatic Cancer ◽  
Invasive Approach ◽  
Anticancer Treatment ◽  
Minimal Damage

AbstractLocally advanced pancreatic cancer is often refractory to conventional therapy, thus warranting new approaches. Irreversible electroporation is an ablative modality that has the potential to deliver targeted anticancer treatment with minimal damage to surrounding structures. Indications for irreversible electroporation in pancreatic cancer patients include palliation for metastatic disease, downstaging for surgery in locally advanced disease, and treatment of local recurrence following operative resection. Benefits of the modality in pancreatic cancer include a minimally invasive approach, precise delivery that minimizes nontarget ablation, and upregulation of anticancer immune response. Early studies have demonstrated an acceptable safety profile for irreversible electroporation; however, more data are needed to define the role of IRE in the treatment algorithm of pancreatic cancer.

scholarly journals Electric Pulses Can Influence Galvanotaxis of Dictyostelium discoideum

2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Ying Li ◽  
Yu Gu ◽  
He Wang ◽  
Zhipeng Liu ◽  
Bing Song ◽  
...  
Keyword(s):  
Wound Healing ◽  
Electric Field ◽  
Dictyostelium Discoideum ◽  
Electric Fields ◽  
Duty Cycle ◽  
Pulse Electric Field ◽  
Underlying Mechanism ◽  
Electric Pulses ◽  
Electric Stimulator ◽  
Pulse Electric

Galvanotaxis, or electrotaxis, plays an essential role in wound healing, embryogenesis, and nerve regeneration. Up until now great efforts have been made to identify the underlying mechanism related to galvanotaxis in various cells under direct current electric field (DCEF) in laboratory studies. However, abundant clinical research shows that non-DCEFs including monopolar or bipolar electric field may also contribute to wound healing and regeneration, although the mechanism remains elusive. Here, we designed a novel electric stimulator and applied DCEF, pulsed DCEF (pDCEF), and bipolar pulse electric field (bpEF) to the cells of Dictyostelium discoideum. The cells had better directional performance under asymmetric 90% duty cycle pDCEF and 80% duty cycle bpEF compared to DCEF, with 10 Hz frequency electric fields eliciting a better cell response than 5 Hz. Interestingly, electrically neutral 50% duty cycle bpEF triggered the highest migration speed, albeit in random directions. The results suggest that electric pulses are vital to galvanotaxis and non-DCEF is promising in both basic and clinical researches.

Adapting the Cassini Curve to Approximate In Vivo Irreversible Electroporation Ablations in Porcine Liver

2013 ◽  
Author(s):  
Paulo A. Garcia ◽  
Christopher B. Arena ◽  
Robert E. Neal ◽  
S. Nahum Goldberg ◽  
Eliel Ben-David ◽  
...  
Keyword(s):  
Cell Death ◽  
Transmembrane Potential ◽  
Tumor Tissue ◽  
Irreversible Electroporation ◽  
Low Energy ◽  
Porcine Liver ◽  
Electric Pulses ◽  
Focal Ablation ◽  
Increase Membrane Permeability

Irreversible electroporation (IRE) is a new minimally invasive non-thermal focal ablation technique that has been used for the treatment of spontaneous tumors in canine and human patients [1, 2]. The procedure typically involves placing two electrodes into or around a tumor and delivering a series of low energy electric pulses to kill tumor tissue with sub-millimeter resolution. The pulses generate an electric field that alters the resting transmembrane potential (TMP) of the cells. Depending on the magnitude of the induced TMP, the electric pulses can have no effect, reversibly increase membrane permeability, or cause cell death in the case of IRE.

Sign in / Sign up

Export Citation Format

Share Document