scholarly journals HyCHEED System for Maintaining Stable Temperature Control during Preclinical Irreversible Electroporation Experiments at Clinically Relevant Temperature and Pulse Settings

Sensors ◽  
2020 ◽  
Vol 20 (21) ◽  
pp. 6227
Author(s):  
Pierre Agnass ◽  
Hans M. Rodermond ◽  
Remko Zweije ◽  
Jan Sijbrands ◽  
Jantien A. Vogel ◽  
...  
Keyword(s):  
Electric Field ◽  
Cell Suspension ◽  
Thermal Effects ◽  
Carcinoma Cell ◽  
Specific Conductivity ◽  
Irreversible Electroporation ◽  
Tumor Cell Suspension ◽  
Stable Temperature ◽  
Significant Temperature ◽  
Temperature Levels

Electric permeabilization of cell membranes is the main mechanism of irreversible electroporation (IRE), an ablation technique for treatment of unresectable cancers, but the pulses also induce a significant temperature increase in the treated volume. To investigate the therapeutically thermal contribution, a preclinical setup is required to apply IRE at desired temperatures while maintaining stable temperatures. This study’s aim was to develop and test an electroporation device capable of maintaining a pre-specified stable and spatially homogeneous temperatures and electric field in a tumor cell suspension for several clinical-IRE-settings. A hydraulically controllable heat exchange electroporation device (HyCHEED) was developed and validated at 37 °C and 46 °C. Through plate electrodes, HyCHEED achieved both a homogeneous electric field and homogenous-stable temperatures; IRE heat was removed through hydraulic cooling. IRE was applied to 300 μL of pancreatic carcinoma cell suspension (Mia PaCa-2), after which cell viability and specific conductivity were determined. HyCHEED maintained stable temperatures within ±1.5 °C with respect to the target temperature for multiple IRE-settings at the selected temperature levels. An increase of cell death and specific conductivity, including post-treatment, was found to depend on electric-field strength and temperature. HyCHEED is capable of maintaining stable temperatures during IRE-experiments. This provides an excellent basis to assess the contribution of thermal effects to IRE and other bio-electromagnetic techniques.

Intramedullary canine spinal cord tumor model

1984 ◽  
Vol 61 (4) ◽  
pp. 761-766 ◽  
Author(s):  
Michael Salcman ◽  
Ernesto Botero ◽  
Krishna C. V. Rao ◽  
Richard D. Broadwell ◽  
Eric Scott
Keyword(s):  
Spinal Cord ◽  
Cell Suspension ◽  
Spinal Cord Tumor ◽  
Calf Serum ◽  
Tumor Model ◽  
Thoracic Spinal Cord ◽  
Content Type ◽  
Tumor Cell Suspension ◽  
Thoracic Spinal ◽  
Ethyl Cyanoacrylate

✓ The development of a transplantable model brain tumor in the neonatal dog, the adaptation of the tumor to tissue culture, and the successful growth of the tumor in adult mongrel dogs has been adapted to producing similar tumors in the thoracic spinal cord of the adult dog. Ten adult dogs, weighing 4 to 25.4 kg each, were subjected to formal laminectomy. The tumor cell suspension was injected by hand with a Hamilton syringe at two or three sites over a distance of 1 cm; each site received an injection volume to 0.02 to 0.05 cc of the cell suspension after the dura had been opened. Immediately after injection the field was copiously irrigated and the puncture area sealed with a single drop of ethyl cyanoacrylate. Tumor cells for injection were obtained by thawing ampules stored at −195°C in a mixture of 10% dimethyl sulfoxide and RPMI 1640 culture medium. Cells were resuspended in Hank's balanced salt solution and 15% fetal calf serum on ice. Solutions had 90% cell viability, and animals received a dose in the range of 3 to 13 × 106 cells. Eight animals developed tumors and became paraparetic on the 9th to 14th postinjection day. Metrizamide myelography in three animals revealed complete blocks; two animals underwent spinal computerized tomography (CT) and demonstrated syringohydromyelia. Histology revealed the tumors to be highly vascular primitive neoplasms that invaded the surrounding cord. This spinal cord tumor model is large enough to be operated on, studied by CT and myelography, and subjected to pharmacological, electrophysiological, and blood flow study.

Effect of Three-Dimensional Electric Field and Heat Conduction to Electrodes on the Temperature Rise During Irreversible Electroporation

2011 ◽  
Author(s):  
Seiji Nomura ◽  
Kosaku Kurata ◽  
Hiroshi Takamatsu
Keyword(s):  
Heat Conduction ◽  
Electric Field ◽  
Temperature Rise ◽  
Heat Conduction Equation ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Three Dimensional ◽  
End Effects ◽  
Abnormal Cells ◽  
Novel Method

The irreversible electroporation (IRE) is a novel method to ablate abnormal cells by applying a high voltage between two electrodes that are stuck into abnormal tissues. One of the advantages of the IRE is that the extracellular matrix (ECM) may be kept intact, which is favorable for healing. For a successful IRE, it is therefore important to avoid thermal damage of ECM resulted from the Joule heating within the tissue. A three-dimensional (3-D) analysis was conducted in this study to predict temperature rise during the IRE. The equation of electric field and the heat conduction equation were solved numerically by a finite element method. It was clarified that the highest temperature rise occurred at the base of electrodes adjacent to the insulated surface. The result was significantly different from a two-dimensional (2-D) analysis due to end effects, suggesting that the 3-D analysis is required to determine the optimal condition.

scholarly journals Cytoskeletal Disruption after Electroporation and Its Significance to Pulsed Electric Field Therapies

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1132 ◽  
Author(s):  
Philip M. Graybill ◽  
Rafael V. Davalos
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Irreversible Electroporation ◽  
Pulsed Electric Fields ◽  
Pulsed Electric Field ◽  
Current Understanding ◽  
Vascular Effects ◽  
Cell Substrate ◽  
Membrane Effects ◽  
Cytoskeletal Disruption

Pulsed electric fields (PEFs) have become clinically important through the success of Irreversible Electroporation (IRE), Electrochemotherapy (ECT), and nanosecond PEFs (nsPEFs) for the treatment of tumors. PEFs increase the permeability of cell membranes, a phenomenon known as electroporation. In addition to well-known membrane effects, PEFs can cause profound cytoskeletal disruption. In this review, we summarize the current understanding of cytoskeletal disruption after PEFs. Compiling available studies, we describe PEF-induced cytoskeletal disruption and possible mechanisms of disruption. Additionally, we consider how cytoskeletal alterations contribute to cell–cell and cell–substrate disruption. We conclude with a discussion of cytoskeletal disruption-induced anti-vascular effects of PEFs and consider how a better understanding of cytoskeletal disruption after PEFs may lead to more effective therapies.

scholarly journals Careful treatment planning enables safe ablation of liver tumors adjacent to major blood vessels by percutaneous irreversible electroporation (IRE)

2015 ◽  
Vol 49 (3) ◽  
pp. 234-241 ◽  
Author(s):  
Bor Kos ◽  
Peter Voigt ◽  
Damijan Miklavcic ◽  
Michael Moche
Keyword(s):  
Electric Field ◽  
Blood Vessels ◽  
Treatment Planning ◽  
Hepatic Vein ◽  
Thermal Ablation ◽  
Pulse Generator ◽  
Liver Tumors ◽  
Irreversible Electroporation ◽  
Distance Ratio ◽  
Contrast Enhanced Ct

AbstractBackground.Irreversible electroporation (IRE) is a tissue ablation method, which relies on the phenomenon of electroporation. When cells are exposed to a sufficiently electric field, the plasma membrane is disrupted and cells undergo an apoptotic or necrotic cell death. Although heating effects are known IRE is considered as non-thermal ablation technique and is currently applied to treat tumors in locations where thermal ablation techniques are contraindicated.Materials and methods.The manufacturer of the only commercially available pulse generator for IRE recommends a voltage-to-distance ratio of 1500 to 1700 V/cm for treating tumors in the liver. However, major blood vessels can influence the electric field distribution. We present a method for treatment planning of IRE which takes the influence of blood vessels on the electric field into account; this is illustrated on a treatment of 48-year-old patient with a metastasis near the remaining hepatic vein after a right side hemi-hepatectomy.Results.Output of the numerical treatment planning method shows that a 19.9 cm3irreversible electroporation lesion was generated and the whole tumor was covered with at least 900 V/cm. This compares well with the volume of the hypodense lesion seen in contrast enhanced CT images taken after the IRE treatment. A significant temperature raise occurs near the electrodes. However, the hepatic vein remains open after the treatment without evidence of tumor recurrence after 6 months.Conclusions.Treatment planning using accurate computer models was recognized as important for electrochemotherapy and irreversible electroporation. An important finding of this study was, that the surface of the electrodes heat up significantly. Therefore the clinical user should generally avoid placing the electrodes less than 4 mm away from risk structures when following recommendations of the manufacturer.

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