Irreversible electroporation (IRE) is a cellular ablation method used to treat a variety of cancers. IRE works by exposing tissues to pulsed electric fields which cause cell membrane disruption. Cells exposed to lower energies become temporarily permeable while greater energy exposure results in cell death. For IRE to be used safely in the brain, methods are needed to extend the area of ablation without increasing applied voltage, and thus, thermal damage. We present evidence that IRE used with adjuvant calcium (5 mM CaCl2) results in a nearly twofold increase in ablation area in vitro compared to IRE alone. Adjuvant 5 mM CaCl2 induces death in cells reversibly electroporated by IRE, thereby lowering the electric field thresholds required for cell death to nearly half that of IRE alone. The calcium-induced death response of reversibly electroporated cells is confirmed by electrochemotherapy pulses which also induced cell death with calcium but not without. These findings, combined with our numerical modeling, suggest the ability to ablate up to 3.2× larger volumes of tissue in vivo when combining IRE and calcium. The ability to ablate a larger volume with lowered energies would improve the efficacy and safety of IRE therapy.
Keywords: Ablation volume; Brain cancer; Combined therapy; Electrochemotherapy; Finite element modeling; Irreversible electroporation.