Radiofrequency ablation (RFA) of non-resectable tumors has been shown to be as effective as surgical resection. During an RFA procedure, the tumor is heated to a temperature sufficient to cause cell death; the RF current is used to heat the tissue and there is no clinically significant electrical interaction within the tissue.
While the intent of thermal therapy is to kill tumor cells, extra-cellular proteins will also be heated and can be denatured leading to permanent damage to the tissue infra-structure including vital structures such as blood vessels, nerves, ducts, etc.. Cooling by blood flow can also impede the killing of tumor cells near a blood vessel and it has been reported that a tumor of perivascular tissue remains viable near vessels greater than 3 mm diameter after RF therapy due to this “heat sink” effect.
Electroporation of tissue has been studied for over 50 years. It is now well known that an external electric field can change the permeability of the cell membrane to molecules, enabling the molecules to flow into the cytoplasm. It is also well known that increasing the electric field in-situ can cause irreversible cell damage leading to cell death without substantially raising the temperature of the tissue. Recently, it has been suggested that irreversible electroporation (IRE) could be a useful alternative to thermal therapies as a method of tumor ablation. Theoretically, non-thermal IRE has some advantages over thermal therapies by eliminating the aforementioned morbidities and the heat sink effect.
More than a single pulse is required to cause cell death with IRE and increasing the number of pulses applies more energy to the tissue, eventually causing heating. A characteristic difference between the RFA waveform and the IRE waveform is that RFA is a true alternating current (AC) waveform while IRE is a monophasic waveform. However, both can cause Joule heating from the conduction current therefore one must pay attention to the total energy.
In this study we examined histopathological tissue changes induced by short pulse/high voltage irreversible electroporation and used finite element modeling (FEM) to correlate the experimental results to electric field and temperature history. The model calculates tissue temperatures and voltage thresholds for operating parameters and geometry. The histology photographs demonstrate the experimental results under the same conditions. Matching the model to the experimental results allows us to understand the type of damage resulting from the electric field threshold and thermal history within each zone.
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