Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry.
Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry.
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DOI：
10.3171/2009.3.jns081348
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发表时间：
2009-10
影响因子：
4.1
通讯作者：
Garris PA
中科院分区：
文献类型：
--
作者：
Bledsoe JM;Kimble CJ;Covey DP;Blaha CD;Agnesi F;Mohseni P;Whitlock S;Johnson DM;Horne A;Bennet KE;Lee KH;Garris PA
新出现的证据支持特定中枢神经系统的调节有助于脑深部电刺激（DBS）和运动皮层刺激（MCS）的临床疗效的假设。因此，实时监测目标区域的神经化学输出可以通过提供机制研究、识别新的候选神经递质和化学引导的刺激电极放置的策略等目标来推进功能性神经外科。作者报告了一种称为无线瞬时神经递质集中系统（WINCS）的设备的开发，用于功能性神经外科手术期间的术中神经化学监测。该设备支持碳纤维微电极（CFM）上的快速扫描循环伏安法（FSCV），用于实时，空间和化学分辨的大脑神经递质测量。FSCV研究包括以300 V/s的速率在−0.4和1 V之间扫描三角波，并以10 Hz施加。将所有电压与Ag/AgCl参比电极进行比较。通过将单个碳纤维（r = 2.5 μm）抽吸到玻璃毛细管中并通过使用移液器拉动毛细管至显微镜尖端来构建CFM。暴露的碳纤维（即传感区域）延伸到玻璃绝缘层之外约100 μm。大多数试验选择神经递质多巴胺作为分析物。原理验证试验包括体外流动注射和噪声分析，以及通过监测内侧前脑束高频电刺激后纹状体中多巴胺释放来监测麻醉大鼠体内测量。与传统的硬连线系统进行了直接比较。WINCS的设计符合FDA认可的医用电气设备安全共识标准，由4个模块组成：1）FSCV前端模拟电路（即电流-电压转换器）; 2）蓝牙收发器; 3）微处理器; 4）直流电池。一台运行定制软件并配备通用串行总线连接蓝牙收发器的Windows-XP笔记本电脑用作基站。计算机软件以100千样本/秒的速度进行无线数据采集，并远程控制FSCV操作和可调波形参数。WINCS提供了可靠的，高保真度的测量多巴胺和其他神经化学物质，如血清素，去甲肾上腺素，抗坏血酸通过使用FSCV在CFM和流动注射分析。在大鼠中，WINCS检测到次秒级纹状体多巴胺释放在植入的传感器在高频刺激的多巴胺能纤维上升。总体而言，体外和体内测试证明了与FSCV的常规硬连线电化学系统相当的信号。重要的是，WINCS降低了对手术室环境中常见的电磁噪声的敏感性。总之，这些结果表明WINCS非常适合术中神经化学监测。预计在植入的化学传感器的神经递质的测量将被证明是有用的推进功能性神经外科。
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. 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. 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. 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.