Perfused organ model development and evaluation for irreversible electroporation investigations

Irreversible electroporation (IRE) is a technique to kill cells by delivering a series of short-duration, high voltage square wave electric pulses into tissue to alter the native cellular transmembrane potential, creating irrecoverable nanoscale defects in the cell membrane. IRE protocols constrain Joule heating below temperatures that cause coagulation of extracellular proteins, and consequently spare critical structures that contraindicate other thermal-based therapies. Tissue-level characterization and optimization of IRE treatment conventionally requires costly and logistically complex in vivo experiments, since affected zones cannot be visualized in expired ex vivo tissue. This has limited IRE protocol evolution. Here, an alternate method using active perfusion of freshly harvested organs with an appropriate viability stain is described, and offers an approach to visualize IRE-affected tissue. The lesions were validated against protocol-matched in vivo trials. This offers an approach to cheaply expedite IRE development, permitting faster protocol and device optimization, ultimately offering better clinical outcomes.