Dynamic effects of point source electroporation on the rat brain tissue

• Unique setup provided intracranial point source combined NTRE/NTIRE in rat brains.
• MRI confirmed spherical reversible BBB disruption surrounding smaller damage volume.
• Treatment effects were confirmed to depend exponentially on treatment parameters.
• Increased voltage or pulse numbers yielded larger BBB disruption and damage volumes.
• BBB disruption volumes were 3.2 ± 0.3 times larger than damage volumes (p < 0.0001).

In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood–brain barrier penetration of most therapeutic agents.In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood–brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r2 = 0.99, p < 0.001) and the number of treatment pulses (r2 = 0.94, p < 0.002). Blood–brain barrier disruption depicted 3.2 ± 0.3 times larger volumes than the final permanent damage volumes (p < 0.0001). These results indicate that it may be beneficial to use more than one modality of electroporation when planning a treatment for brain tumors.