Nonthermal Irreversible Electroporation as a Focal Ablation Treatment for Brain Cancer

Abstract

Irreversible Electroporation (IRE) is a new focal tissue ablation technique that has shown great promise as a treatment for a variety of soft-tissue neoplasms. The therapy uses pulsed electric fields to destabilize cell membranes and achieve tissue death in a non-thermal manner. The procedure is minimally invasive and is performed through small electrodes inserted into the tissue with treatment duration of about 1 min. In this chapter we describe the first systematic in vivo studies of IRE in canine brain tissue. We confirmed that the procedure can be applied safely in the brain and was well tolerated clinically in normal dogs. The necrotic lesions created with IRE were sub-millimeter in resolution, sharply delineated from normal brain, and spared the major blood vessels. In addition, our preliminary results in a rodent study indicate that IRE transiently disrupts the BBB adjacent to the ablated area in a voltage-dependent manner with implications for enhanced delivery of cytotoxic agents to regions with infiltrative tumor cells. Finally, we present representative case examples demonstrating therapeutic planning aspects, clinical applications, and results of IRE ablation of spontaneous malignant intracranial gliomas in canine patients. Our group has demonstrated that IRE ablation can be performed safely, and is effective at reducing the tumor volume and associated intracranial hypertension, and allows for improvement in tumor-associated neurologic dysfunction. Our work illustrates the potential benefits of IRE for in vivo ablation of neoplastic brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal.