Statistical Modeling And Parameter Optimization Of Irreversible Electroporation For Cervical Cancer Cells In Vitro

Irreversible electroporation(IRE)is a new type of tumor ablation technique,which can induce many irreversible small holes on the cell membrane by repeated stimulation of high-voltage pulses,leading to cell death so as to eliminate the tumor.Due to the heterogeneous characteristics of ttumors,the IRE treatment in the target zone can lead to the incomplete tumor ablation,which further leads to local tumor recurrence.The computer model can be used as a predictor of IRE treatment outcomes to provide guidances and protocol designs in clinic to prevent the recurrence of tumors.But the previous model based on the theory of IRE threshold is not accurate and can not reflect the actual ablation process comprehensively,which limits the instructive significance of the simulation results to the clinic.In order to solve this problem,this thesis aims to build a more accurate IRE statistical model predicting treatment effects of IRE for cervical cancers so as to improve the instructive significance of the model to clinical operation.The main work of this thesis is as follows:(1)An effective method to measure the viability of cervical cancer cells was determined firstly by conducting in vitro experiments of IRE to cervical cancer cells,and then the IRE statistical model of cervical cancer was established based on the experimental data and modified Peleg model.(2)The comparison between IRE statistical model and the IRE threshold model was used to validate the feasibility of IRE statistical model.(3)Three-dimensional cervical cancer tissue model was established in COMSOL based on IRE statistical model.The pulse voltage and structure of electrode needle(distance,diameter and length of needles)were optimized by using response surface method.The results concluded that:(1)The cervical cancer cell viability can be accurately measured when the cells were stained using Trypan blue at 4 h incubation immediately after the IRE experiment.(2)Compared with the IRE threshold model,the IRE statistical model established in this thesis is more accurate in reflecting the effect of IRE ablation.(3)Compared with the three electrodes and four electrodes,using two electrodes can achieve the largest area of tumor ablation with the minimal damage to normal tissue,and the area of the two electrodes ablation is more rounded and controllable.