Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry

Technical note

Jonathan M. Bledsoe M.D.1, Christopher J. Kimble M.A.2, Daniel P. Covey B.S.3, Charles D. Blaha Ph.D.4, Filippo Agnesi M.S.5, Pedram Mohseni Ph.D.6, Sidney Whitlock B.S.2, David M. Johnson B.S.2, April Horne B.S., M.B.A.2, Kevin E. Bennet B.S.Ch.E., M.B.A.2, Kendall H. Lee M.D., Ph.D.1,5, and Paul A. Garris Ph.D.3
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  • 1 Department of Neurologic Surgery,
  • | 2 Division of Engineering, and
  • | 5 Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota;
  • | 3 Department of Biological Sciences, Illinois State University, Normal, Illinois;
  • | 4 Department of Psychology, University of Memphis, Tennessee; and
  • | 6 Department of Electrical Engineering and Computer Science, Case Western Reserve University, Cleveland, Ohio
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Object

Emerging evidence supports the hypothesis that modulation of specific central neuronal systems contributes to the clinical efficacy of deep brain stimulation (DBS) and motor cortex stimulation (MCS). Real-time monitoring of the neurochemical output of targeted regions may therefore advance functional neurosurgery by, among other goals, providing a strategy for investigation of mechanisms, identification of new candidate neurotransmitters, and chemically guided placement of the stimulating electrode. The authors report the development of a device called the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for intraoperative neurochemical monitoring during functional neurosurgery. This device supports fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM) for real-time, spatially and chemically resolved neurotransmitter measurements in the brain.

Methods

The FSCV study consisted of a triangle wave scanned between −0.4 and 1 V at a rate of 300 V/second and applied at 10 Hz. All voltages were compared with an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single carbon fiber (r = 2.5 μm) into a glass capillary and pulling the capillary to a microscopic tip by using a pipette puller. The exposed carbon fiber (that is, the sensing region) extended beyond the glass insulation by ~ 100 μm. The neurotransmitter dopamine was selected as the analyte for most trials. Proof-of-principle tests included in vitro flow injection and noise analysis, and in vivo measurements in urethane-anesthetized rats by monitoring dopamine release in the striatum following high-frequency electrical stimulation of the medial forebrain bundle. Direct comparisons were made to a conventional hardwired system.

Results

The WINCS, designed in compliance with FDA-recognized consensus standards for medical electrical device safety, consisted of 4 modules: 1) front-end analog circuit for FSCV (that is, current-to-voltage transducer); 2) Bluetooth transceiver; 3) microprocessor; and 4) direct-current battery. A Windows-XP laptop computer running custom software and equipped with a Universal Serial Bus–connected Bluetooth transceiver served as the base station. Computer software directed wireless data acquisition at 100 kilosamples/second and remote control of FSCV operation and adjustable waveform parameters. The WINCS provided reliable, high-fidelity measurements of dopamine and other neurochemicals such as serotonin, norepinephrine, and ascorbic acid by using FSCV at CFM and by flow injection analysis. In rats, the WINCS detected subsecond striatal dopamine release at the implanted sensor during high-frequency stimulation of ascending dopaminergic fibers. Overall, in vitro and in vivo testing demonstrated comparable signals to a conventional hardwired electrochemical system for FSCV. Importantly, the WINCS reduced susceptibility to electromagnetic noise typically found in an operating room setting.

Conclusions

Taken together, these results demonstrate that the WINCS is well suited for intraoperative neurochemical monitoring. It is anticipated that neurotransmitter measurements at an implanted chemical sensor will prove useful for advancing functional neurosurgery.

Abbreviations used in this paper:

AP = anteroposterior; CFM = carbonfiber microelectrode; DBS = deep brain stimulation; DV = dorsoventral; FSCV = fast-scan cyclic voltammetry; GABA = γ-aminobutyric acid; HFS = high-frequency stimulation; MCS = motor cortex stimulation; MFB = medial forebrain bundle; ML = mediolateral; PD = Parkinson disease; RAT = Real-Time Animal Telemetry; SNc = substantia nigra pars compacta; STN = subthalamic nucleus; UEI = Universal Electrochemistry Instrument; WINCS = Wireless Instantaneous Neurotransmitter Concentration System.

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