Abstract：
We present a numerical method for studying reversible electroporation on normal and cancerous cervical cells. This microdosimetry analysis builds on a unique approach for extracting contours of free and overlapping cervical cells in the cluster from the Extended Depth of Field (EDF) images. The algorithm used for extracting the contours is a joint optimization of multiple-level set function along with the Gaussian mixture model and Maximally Stable Extremal Regions. These contours are then exported to a multi-physics domain solver, where a variable frequency pulsed electric field is applied. The trans-Membrane voltage (TMV) developed across the cell membrane is computed using the Maxwell equation coupled with a statistical approach, employing the asymptotic Smoluchowski equation. The numerical model was validated by successful replication of existing experimental configurations that employed low-frequency uni-polar pulses on the overlapping cells to obtain reversible electroporation, wherein, several overlapping clumps of cervical cells were targeted. For high-frequency calculation, a combination of normal and cancerous cells is introduced to the computational domain. The cells are assumed to be dispersive and the Debye dispersion equation is used for further calculations. We also present the resulting strength-duration relationship for achieving the threshold value of electroporation between the normal and cancerous cervical cells due to their size and conductivity differences. The dye uptake modulation during the high-frequency electric field electroporation is further advocated by a mathematical model.
摘要：
我们提出了一种数值方法，用于研究正常和癌性宫颈细胞上的可逆电穿孔。这种微剂量学分析建立在一种独特的方法上，用于从扩展景深（EDF）图像中提取簇中自由和重叠的宫颈细胞的轮廓。用于提取轮廓的算法是多级集函数以及高斯混合模型和最大稳定极值区域的联合优化。然后将这些轮廓导出到多物理域求解器，其中施加可变频率脉冲电场。跨细胞膜产生的跨膜电压（TMV）是使用麦克斯韦方程结合统计方法计算的，采用渐近Smoluchowski方程。通过在重叠细胞上使用低频单极脉冲以获得可逆电穿孔的现有实验配置的成功复制来验证数值模型。其中，靶向几个重叠的宫颈细胞团块.对于高频计算，将正常细胞和癌细胞的组合引入计算域。假设单元是色散的，并使用德拜色散方程进行进一步计算。我们还介绍了由于正常和癌性宫颈细胞的大小和电导率差异，因此在正常和癌性宫颈细胞之间实现电穿孔阈值的强度-持续时间关系。数学模型进一步倡导了高频电场电穿孔过程中的染料吸收调制。
