Design an irreversible electroporation experimental apparatus: An approach to estimate and optimize the IRE dose

Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths in occidental countries. The options for the treatment of pancreatic cancer that are currently available are limited, with surgical resection remaining as the only curative method. Still, the survival rates for patients that undergo surgery are very low. Irreversible Electroporation (IRE) is an emerging technique that has drawn attention in the field of cancer treatment. By inserting electrodes in soft tissue, pulsed electrical fields are delivered to the cells, creating lethal nanopores in the plasmamembrane to induce cell death. There are several parameters that may influence the outcomes of IRE for a given tissue organ type. These parameters establish the IRE dose of the treatment. However, the application of this technique may result in undesired thermal damage of the tissue if the correct doses are not administered. In fact, the optimal combination of parameters is still unknown, whereby the efficiency of this technique can still be improved. As a result, the optimal IRE dose for pancreatic cancer is investigated in this project. Parameters such as the number of delivered pulses, their amplitude and width were adjusted. In addition, the influence of the distance between the inserted electrodes and their active length were also studied. 2D simulation models were created to evaluate IRE outcomes such as the generated electric field and temperature changes in the tissue. Experiments were conducted using bovine liver tissue to measure the temperature increase during IRE. The temperature measurements obtained from the experiments were then used to validate the results obtained from the simulation models. The models were successfully validated for biological tissue when the electrodes were inserted in the tissue separated by distances between 10 and 20 mm. Furthermore, statistical analysis revealed significant influence of the distance between the electrodes, the pulse width and the voltage on the temperature achieved in the tissue after IRE. Once validated, optimization of the IRE dose was done for the treatment of pancreatic cancer. The optimal dose was calculated using data from the validated models. The optimal parameters produced an electric field magnitude of 3296.1 V/cm between the electrodes and a maximum temperature of 46.796±C in the tissue surface. No thermal damage in pancreatic tissue is expected after applying an IRE treatment with this optimal dose.