Abstracts

Rationale: Currently, the Responsive Neurostimulation System (RNS) is the only intracerebral neuromodulation therapy approved by the U.S. FDA for the treatment of intractable focal-onset epilepsy. RNS depth electrodes’ neural area of activation only extends 4mm from the surface of the stimulating electrode contact. Extending the active cylindrical depth contact’s area of influence by just 1mm would dramatically increase the ellipsoidal volume of activation. One method for increasing the extent of activation is to enhance the conductivity of the brain adjacent to the electrode. Our study demonstrates both the safety and potential influence of functionalized carbon nanotubes (f-CNTs) to extend the area of activation adjacent to a depth electrode. Both computational modeling and experimental validation were employed.Methods: Cytotoxicity Testing To confirm that CNTs could be safely used in the brain, human astrocytes (HA) isolated from the cerebral cortex were obtained from ScienCell and cultured per ATCC protocols. The HA were treated with both raw and chemically-functionalized metallic CNTs of 90, 95, and 99% purity (NanoIntegris). Cell viability was measured 72 hours post-treatment via an alamar blue assay (Invitrogen). Computational Modeling of the Influence of CNTs on the Extent of Activation To quantify the potential influence on the area of activation for direct neurostimulation, a computational model of the depth electrodes, isotropic white matter, and localized delivery of f-CNTs were created. Using COMSOL Multiphysics, simulations of the influence of f-CNTs within the diffusion area regarding electric potential were performed relative to a 100Hz asymmetric charge-balanced waveform. Experimental Modeling of the Influence of Carbon Nanotubes on the Extent of Activation To confirm the computational modeling, a Type VII culture-grade agarose gel phantom which replicates both the conductivity and porosity of brain tissue was cast around an Ad-Tech 1.12mm diameter depth electrode. An A-M Systems 3800 stimulator was used to create the aforementioned waveform. Recording electrodes connected to a Rigol 100MHz bandwidth digital oscilloscope were used to observe the change in the signal after metallic 99% pure f-CNTs were delivered.Results: Upon performing a student’s t-test, the HA viability testing determined that at 25 ng/mL, raw 90% pure metallic-type CNTs reduced HA viability relative to raw 99% pure metallic-type CNTs (p<0.05). No statistically significant difference in HA viabilities was observed for f-CNTs. The computational modeling indicated that the area of diffusion of CNTs acted as an extension of the active electrode contact during stimulation due to the high conductivity value of CNTs. This result was corroborated experimentally.Conclusions: Functionalized metallic-type CNTs are biocompatible within the brain and could serve as a way to enhance the volume of activation by an electrode via direct neurostimulation. Such augmentation of the neural milieu surrounding the depth electrode can interface with and activate a greater extent of the epileptogenic circuit.