CELL MORPHOLOGY-BASED CHARACTERIZATION OF THE IRREVERSIBLE ELECTROPORATION FOR TUMOR ABLATION

Irreversible Electroporation (IRE) stands at the forefront of contemporary tumor ablation research. An in-depth understanding of how cells with different morphologies respond to various IRE protocols is crucial for assessing their vulnerability to such ever-changing cancer treatment. In short, this relationship is called throughout this thesis. This thesis study was motivated to explore this relationship based on an in vitro IRE experiment of single cells. The results of the study affirmed the influence of cell morphological features on its susceptibility to IRE treatment. The simulations in the study spotlighted how distinct morphological features impact the distribution of transmembrane potential (TMP) over a threshold value on the plasma membrane. The experimental data in the study, shifting from in silico to in vitro, highlighted disparities in lethal areas for different tumor cells under identical IRE protocols. The study also correlated the membrane occupancy of where TMP over a specific threshold value with the lethal area from in vitro IRE experiments, to improve our understanding of the vulnerability of cells in the context of IRE as well as the pivotal role of their morphology. This study developed a quantitative expression of this relationship, which was also called single cell electroporation (SCE) model, because the relationship also contains the information of cell lethal to IRE. Therefore, the SCE model is useful to guide the IRE operation in the clinical setting, especially promoting the current thinking in medicine, i.e., personalised medicine. This thesis has made a few scientific contributions: (1) Provision of a method along with its tool to automate the extraction of cell morphology along with features, enabling to process thousands of cells per image efficiently; (2) Confirmation of the influence of cell morphology on the distribution of TMP exceeding a critical threshold on the cell membrane; (3) Confirmation of the view that cell morphological features affect the vulnerability of the cell to IRE; (4) Finding of a statistical correlation between the membrane occupancy of where local TMP above the threshold value and the lethal area of cells under the influence of IRE stimulus