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OBJECTIVE Treatment of CNS disorders suffer from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). High-frequency electroporation (HFE) employs a series of high voltage pulsed electric fields to disrupt the BBB and/or ablate tumor tissue while sparring proteinaceous structures. Pulsing parameters pulse width and intra-phase delay can be modulated to reduce excitation of muscle and nervous tissues, though this is inherently accompanied by an increase in thresholds for ablation in non-CNS tissues. Here, we investigate the effects of pulse width and intra-phase delay on intracranial tissue for BBB disruption (BBBD) in an in vivo healthy rodent model. METHODS 18 male Fisher rats underwent craniectomy procedure and two blunt tipped monopolar electrodes were advanced into the brain for HFE therapy. 200 bursts of HFE were delivered at a voltage-to-distance ratio 600 V/cm. BBBD was verified with contrast enhanced T1W MRI (gadopentetate dimeglumine) and pathologically (Evans blue dye). RESULTS Gross pathological sections and contrast enhanced T1W scans demonstrated BBBD for 2-2-2 µs (n = 4, 36.6 ± 9.4 mm3, 36.7 ± 13.0 mm3), 2-5-2 µs (n = 4, 74.1 ± 7.7 mm3, 74.7 ± 9.8 mm3), 5-2-5 µs (n = 4, 53.9 ± 8.1 mm3, 59.2 ± 10.8 mm3), 5-5-5 µs (n = 4, 81.2 ± 7.9 mm3, 84.1 ± 8.7 mm3), and 10-1-10 µs (n = 2, 61.0 ± 2.8 mm3, 60.0 ± 4.2 mm3) HFE. Histologically, tissue damage was restricted to electrode insertion tracks. BBBD was induced with minimal muscle contractions and minimal cell death attributed to HFE. Numerical modeling indicated the threshold for HFE-mediated BBBD as low magnitude electric fields (&amp;lt; 201 V/cm). These data suggest HFE-mediated BBBD is only modestly affected by changes in pulse width and intra-phase delay.

neuro-oncology

SURG-41. BLOOD-BRAIN BARRIER DISRUPTION WITH HIGH-FREQUENCY ELECTROPORATION IN VIVO: A PRELIMINARY INVESTIGATION DEMONSTRATING THE EFFECTS OF VARIED PULSE WIDTHS AND INTRA-PHASE DELAYS