A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption
Introduction: Electroporation-based therapies such as electrochemotherapy (ECT) and irreversible electroporation (IRE) are emerging as promising tools for treatment of tumors. In the brain electroporation can also induce transient blood-brain-barrier (BBB) disruption in volumes extending beyond IRE. An important key of treatment success is individual treatment planning.
Material and methods: The main objective of this study was to develop a statistical model for prediction of cell death and BBB disruption induced by electroporation, based on the Peleg-Fermi model in combination with numerical models. The model calculates the electric field thresholds for cell kill and BBB disruption and describes the dependence on the number of treatment pulses. The model was validated using in vivo experimental data consisting of rats brains MRIs post electroporation treatments.
Results: Linear regression analysis confirmed that the model described the IRE and BBB disruption volumes as a function of treatment pulses number well(r2=0.79;p<0.008,r2=0.91;p<0.001).The results presented a strong plateau effect as the pulse number increased. The ratio between complete cell death and no cell death thresholds was relatively narrow (between 0.88-0.91) even for small numbers of pulses and depended weakly on the number of pulses. For BBB disruption, the ratio increased with the number of pulses. BBB disruption radii were on average 67%±11%larger than IRE volumes suggesting good coverage surrounding the IRE region.
Conclusions: The statistical model can be used to describe the dependence of treatment-effects on the number of pulses independent of the experimental setup.