title: Comprehensive characterization and failure modes of tungsten microwire arrays in chronic neural implants.
abstract: For nearly 55 years, tungsten microwires have been widely used in neurophysiological experiments in animal models to chronically record neuronal activity. While tungsten microwires initially provide stable recordings, their inability to reliably record high-quality neural signals for tens of years has limited their efficacy for neuroprosthetic applications in humans. Comprehensive understanding of the mechanisms of electrode performance and failure is necessary for developing next generation neural interfaces for humans. In this study, we evaluated the abiotic (electrophysiology, impedance, electrode morphology) and biotic (microglial reactivity, blood-brain barrier disruption, biochemical markers of axonal injury) effects of 16-channel, 50 µm diameter, polyimide insulated tungsten microwires array for implant durations that ranged from acute to up to 9 months in 25 rats. Daily electrode impedance spectroscopy, electrophysiological recordings, blood and cerebrospinal fluid (CSF) withdrawals, and histopathological analysis were performed to study the time-varying effects of chronic electrode implantation. Structural changes at the electrode recording site were observed as early as within 2-3 h of electrode insertion. Abiotic analysis indicated the first 2-3 weeks following surgery was the most dynamic period in the chronic electrode lifetime as there were greater variations in the electrode impedance, functional electrode performance, and the structural changes occurring at the electrode recording tips. Electrode recording site deterioration continued for the long-term chronic animals as insulation damage occurred and recording surface became more recessed over time. In general, electrode impedance and functional performance had smaller daily variations combined with reduced electrode recording site changes during the chronic phase. Histopathological studies were focused largely on characterizing microglial cell responses to electrode implantation. We found that activated microglia were present near the electrode tracks in all non-acute animals studied, thus indicating presence of a neuroinflammatory response regardless of post-implantation survival times and electrode performance. Conversely, dystrophic microglia detectable as fragmented cells were found almost exclusively in acute animals surviving only few hours after implantation. While there was no consistent relationship between microglial cell responses and electrode performance, we noticed co-occurrence of high ferritin expression, intraparenchymal bleeding, and microglial degeneration suggesting presence of excessive oxidative stress via Fenton chemistry. Biochemical analysis indicated that these electrodes always caused a persistent release of axonal injury biomarkers even several months after implantation suggesting persistent tissue damage. Our study suggests that mechanisms of electrode failure are multi-factorial involving both abiotic and biotic parameters. Since these failure modes occur concurrently and cannot be isolated from one another, the lack of consistent relationship between electrode performance and microglial responses in our results suggest that one or more of the abiotic factors were equally responsible for degradation in electrode performance over long periods of time.
authors.affiliation: Department of Biomedical Engineering, University of Miami, FL, USA. a.prasad@miami.edu
authors.forename: Abhishek
authors.initials: A
authors.lastname: Prasad
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Xue
authors.forename: Viswanath
authors.initials: V
authors.lastname: Sankar
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nishida
authors.forename: Gerry
authors.initials: G
authors.lastname: Shaw
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Streit
authors.forename: Justin C
authors.initials: JC
authors.lastname: Sanchez
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology* / Q000648:ultrastructure*; D017097:Electric Impedance; D004567:Electrodes, Implanted / Q000592:standards*; D004868:Equipment Failure; D008297:Male; D008839:Microelectrodes / Q000592:standards*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014414:Tungsten / Q000737:chemistry
chemical_list: D014414:Tungsten