scholarly journals High Frequency Electroporation for Cancer Therapy

2011 ◽  
Author(s):  
Christopher B. Arena ◽  
Michael B. Sano ◽  
Marissa Nichole Rylander ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
High Frequency ◽  
Thermal Injury ◽  
Transmembrane Potential ◽  
Irreversible Electroporation ◽  
Chemotherapeutic Drugs ◽  
Reversible Electroporation ◽  
Biophysical Mechanism ◽  
Membrane Defects

Electroporation is a non-linear biophysical mechanism in which the application of an external pulsed electric field leads to an increase in the permeability of cellular membranes. The extent of electroporation is attributed to the induced buildup of charge across the membrane, and consequently, transmembrane potential (TMP). Increasing the TMP has been described to produce various permeabilizing effects, wherein the formation of hydrophilic, aqueous pores becomes energetically favorable [1]. If the pulse parameters are tuned such that the membrane defects are only temporary, and the cell remains viable, the process is termed reversible electroporation. As a cancer therapy, reversible electroporation has been employed to increase the cellular uptake of chemotherapeutic drugs. Irreversible electroporation (IRE) results when membrane defects are permanent, leading to cell death. Recently, IRE has been recognized as an independent means to destroy tumors without the use of adjuvant drugs and prior to the onset of thermal injury [2].

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.

scholarly journals High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity

EBioMedicine ◽  
2019 ◽  
Vol 44 ◽  
pp. 112-125 ◽  
Author(s):  
Veronica M. Ringel-Scaia ◽  
Natalie Beitel-White ◽  
Melvin F. Lorenzo ◽  
Rebecca M. Brock ◽  
Kathleen E. Huie ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Immunity ◽  
High Frequency ◽  
Irreversible Electroporation ◽  
Tumor Ablation

High frequency irreversible electroporation (H-FIRE) as a novel method of targeted cell death.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 277-277
Author(s):  
Imran A Siddiqui ◽  
Russell C. Kirks ◽  
Erin H Baker ◽  
Eduardo Latouche ◽  
Matt Dewitt ◽  
...  
Keyword(s):  
Cell Death ◽  
High Frequency ◽  
Irreversible Electroporation ◽  
Vital Signs ◽  
Cardiac Monitoring ◽  
Vascular Integrity ◽  
Cancer Cell Death ◽  
Novel Method ◽  
Vascular Structures ◽  
Cardiac Synchronization

277 Background: Irreversible electroporation unlike ablation is excellent in inducing cell death via apoptosis. It, however, has disadvantages of electrical conduction via cardiac and nervous tissue. This results in requiring cardiac monitoring and general anesthesia and paralytics while performing electroporation. We hypothesized a novel high-frequency IRE (H-FIRE) system employing ultra-short bipolar pulses would obviate the need for cardiac synchronization and paralytics while maintaining measurable effect on cell death. Methods: Female swine (55-65Kg) were used. Two H-FIRE electrodes were inserted into the liver (1.5-cm spacing). In the absence of paralytics H-FIRE pulses were delivered (2250V, 2-5-2 pulse configuration) at different on times (100 vs. 200μs) or number of pulses (100 vs. 300). Next electrodes were placed across major hepatic vascular structures and H-FIRE performed. At conclusion tissue was resected and analyzed histologically. Results: 24 H-FIREs were performed (mean ablation time 275 secs). No EKG abnormalities or changes in vital signs were measured during H-FIRE procedures. In 1/24 H-FIREs minor twitching of the rectus abdominis was recorded coinciding with pulse delivery. Histologically, tissues had effective electroporation as evidenced by cell death and caspase activity. Blinded scoring was performed for necrosis and apoptosis. Areas of cell death were predictable. No significant vascular damage or coagulated/thermally-desiccated blood was detected within major vessels following H-FIRE. Conclusions: H-FIRE is a novel way of liver electroporation. It produces predictable cell apoptosis without the requirement of paralytics and alteration of electrocardiographic signals as compared to traditional electroporation, while preserving underlying vascular integrity. Its application in cancer cell death needs to be further studied, but it has a potential for clinical use in targeting tumors with minimal morbidity and associated cardiac and neurologic side effects.

Phase Change Electrodes for Reducing Joule Heating During Irreversible Electroporation

2012 ◽  
Author(s):  
Christopher B. Arena ◽  
Roop L. Mahajan ◽  
Marissa Nichole Rylander ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Electric Fields ◽  
Electric Field Distribution ◽  
Irreversible Electroporation ◽  
Tissue Ablation ◽  
Thermal Processes ◽  
Ablation Volume ◽  
Extracellular Matrix Components ◽  
Membrane Defects ◽  
Viable Treatment

Irreversible electroporation (IRE) is a non-thermal tissue ablation modality that is gaining momentum as a viable treatment option for tumors and other non-cancerous pathologies [1]. The protocol consists of delivering a series of short (∼ 100 μs) and intense (∼ 1000 V/cm) pulsed electric fields through electrodes inserted directly into or around a targeted tissue. The pulses induce a rapid buildup of charge across the plasma membrane of cells comprising the tissue that results in the creation of permanent membrane defects, ultimately leading to cell death. Because the extent of cell death relies predominately on the extent of charge buildup and not thermal processes, extracellular matrix components are spared, including major nerve and blood vessel architecture. Additionally, the ablation volume is predictable based on the electric field distribution and visible in real-time via MRI, CT, and ultrasound.

Irreversible Electroporation (IRE) to Treat Brain Tumors

2008 ◽  
Author(s):  
Paulo A. Garcia ◽  
John Robertson ◽  
John Rossmeisl ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Brain Tumors ◽  
High Voltage ◽  
Electric Pulse ◽  
Irreversible Electroporation ◽  
Transient Effect ◽  
Electric Pulses ◽  
Thermal Cell ◽  
Reversible Electroporation

Electroporation is the phenomenon in which permeability of the cell membrane to ions and macromolecules is increased by exposing the cell to short (microsecond to millisecond) high voltage electric pulses [1]. The application of the electric pulse can have no effect, can have a transient effect known as reversible electroporation, or can cause permanent permeation known as irreversible electroporation (IRE) which leads to non-thermal cell death by necrosis [1, 2].

An In Vitro Study on Adjuvant Enhanced Irreversible Electroporation

2012 ◽  
Author(s):  
Chunlan Jiang ◽  
Zhenpeng Qin ◽  
Gary Long ◽  
John C. Bischof
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Thermal Injury ◽  
Irreversible Electroporation ◽  
Membrane Integrity ◽  
In Vitro Study ◽  
Connective Tissues ◽  
Careful Choice ◽  
Electrical Pulses

Recently, irreversible electroporation (IRE) has emerged as a promising tumor ablation technique. IRE induces cell death by irreversibly compromising membrane integrity with a series of short, high voltage electrical pulses [1]. IRE offers many advantages over surgery and thermal ablations including that it 1) is fast and minimally invasive, 2) destroys the tumor while preserving adjacent connective tissues [2], and 3) can be delivered with negligible thermal injury [3]. Here we hypothesize that the thresholds necessary to successfully electroporate cancer cell membranes, and therefore more effectively destroy an entire tumor, can be dramatically improved by careful choice of 1) electroporation parameter, and 2) chemical adjuvants that specifically impact the cell membrane.

scholarly journals Ablation Modalities for Therapeutic Intervention in Arrhythmia-Related Cardiovascular Disease: Focus on Electroporation

2021 ◽  
Vol 10 (12) ◽  
pp. 2657
Author(s):  
Shauna McBride ◽  
Sahar Avazzadeh ◽  
Antony M. Wheatley ◽  
Barry O’Brien ◽  
Ken Coffey ◽  
...  
Keyword(s):  
Cell Death ◽  
Irreversible Electroporation ◽  
Structural Heart Disease ◽  
Electrical Energy ◽  
Cell Types ◽  
Fine Tuning ◽  
Specific Cell ◽  
Negative Effects ◽  
Reversible Electroporation ◽  
Disease Focus

Targeted cellular ablation is being increasingly used in the treatment of arrhythmias and structural heart disease. Catheter-based ablation for atrial fibrillation (AF) is considered a safe and effective approach for patients who are medication refractory. Electroporation (EPo) employs electrical energy to disrupt cell membranes which has a minimally thermal effect. The nanopores that arise from EPo can be temporary or permanent. Reversible electroporation is transitory in nature and cell viability is maintained, whereas irreversible electroporation causes permanent pore formation, leading to loss of cellular homeostasis and cell death. Several studies report that EPo displays a degree of specificity in terms of the lethal threshold required to induce cell death in different tissues. However, significantly more research is required to scope the profile of EPo thresholds for specific cell types within complex tissues. Irreversible electroporation (IRE) as an ablative approach appears to overcome the significant negative effects associated with thermal based techniques, particularly collateral damage to surrounding structures. With further fine-tuning of parameters and longer and larger clinical trials, EPo may lead the way of adapting a safer and efficient ablation modality for the treatment of persistent AF.

scholarly journals An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields

2021 ◽  
Vol 14 (12) ◽  
pp. 1333
Author(s):  
Melvin F. Lorenzo ◽  
Sabrina N. Campelo ◽  
Julio P. Arroyo ◽  
Kenneth N. Aycock ◽  
Jonathan Hinckley ◽  
...  
Keyword(s):  
Cell Death ◽  
Blood Brain Barrier ◽  
Electric Fields ◽  
Large Volume ◽  
High Frequency ◽  
Brain Barrier ◽  
Blood Brain ◽  
Cell Ablation ◽  
Reversible Electroporation ◽  
The Brain

The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing. BBB disruption was verified with contrast T1W MRI and pathologically with Evans blue dye. High-frequency irreversible electroporation cell death of healthy rodent astrocytes was investigated in vitro using a collagen hydrogel tissue mimic. Numerical analysis was conducted to determine the electric fields in which BBB disruption and cell ablation occur. Differences between the BBB disruption and ablation thresholds for each waveform are as follows: 2-2-2 μs (1028 V/cm), 5-2-5 μs (721 V/cm), 10-1-10 μs (547 V/cm), 2-5-2 μs (1043 V/cm), and 5-5-5 μs (751 V/cm). These data suggest that HF-PEFs can be fine-tuned to modulate the extent of cell death while maximizing peri-ablative BBB disruption. Furthermore, numerical modeling elucidated the diffuse field gradients of a single-needle grounding pad configuration to favor large-volume BBB disruption, while the monopolar probe configuration is more amenable to ablation and reversible electroporation effects.

High-frequency Irreversible Electroporation Brain Tumor Ablation: Exploring the Dynamics of Cell Death and Recovery

2021 ◽  
pp. 108001
Author(s):  
Kelsey R. Murphy ◽  
Kenneth N. Aycock ◽  
Alayna N. Hay ◽  
John H. Rossmeisl ◽  
Rafael V. Davalos ◽  
...  
Keyword(s):  
Cell Death ◽  
Brain Tumor ◽  
High Frequency ◽  
Irreversible Electroporation ◽  
Tumor Ablation

scholarly journals Evaluation of electroporated area using 2,3,5-triphenyltetrazolium chloride in a potato model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seung Jeong ◽  
Hongbae Kim ◽  
Junhyung Park ◽  
Ki Woo Kim ◽  
Sung Bo Sim ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Irreversible Electroporation ◽  
Tissue Ablation ◽  
Target Tissue ◽  
Triphenyltetrazolium Chloride ◽  
Tissue Model ◽  
Electric Pulses ◽  
Reversible Electroporation ◽  
Over Time

AbstractIrreversible electroporation (IRE) is a tissue ablation method, uses short high electric pulses and results in cell death in target tissue by irreversibly permeabilizing the cell membrane. Potato is commonly used as a tissue model for electroporation experiments. The blackened area that forms 12 h after electric pulsing is regarded as an IRE-ablated area caused by melanin accumulation. Here, the 2,3,5-triphenyltetrazolium chloride (TTC) was used as a dye to assess the IRE-ablated area 3 h after potato model ablation. Comparison between the blackened area and TTC-unstained white area in various voltage conditions showed that TTC staining well delineated the IRE-ablated area. Moreover, whether the ablated area was consistent over time and at different staining times was investigated. In addition, the presumed reversible electroporation (RE) area was formed surrounding the IRE-ablated area. Overall, TTC staining can provide a more rapid and accurate electroporated area evaluation.

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