应用甲醛固定人尸体模型植入皮层微电极阵列的外科训练
Summary
我们设计了一个程序, 其中一个甲醛固定的人的尸体是用来协助外科的训练, 将微电极阵列植入人脑的大脑皮层。
Abstract
本议定书描述了一个程序, 以协助外科医生在训练植入微电极阵列到人脑的大脑皮层。最近的技术进步使制造的微电极阵列, 使记录的活动, 多个单独的神经元在大脑皮层的人脑。这些阵列有可能带来独特的洞察力的神经元关联的大脑功能的健康和疾病。此外, 意志神经元活动的识别和解码打开了建立脑机接口的可能性, 从而有助于恢复失去的神经功能。皮层微电极阵列的植入是一种侵入性的手术, 需要超 centimetric 开颅和皮质表面的暴露;因此, 该程序必须由训练有素的神经外科医生执行。为了提供一个外科训练的机会, 我们设计了一个基于人体尸体模型的程序。使用甲醛固定的人类尸体绕过了动物 (特别是非人灵长类) 外科手术的实际、伦理和财政困难, 同时保持头部、头骨、脑膜和脑的宏观结构表面和允许逼真, 操作室式定位和仪表。此外, 人类尸体的使用比任何非人类模型更接近临床的日常实践。尸体模拟的主要缺点是缺乏脑搏动和血液和脑脊液循环。我们建议, 一个甲醛固定的人体模型是一个适当的, 切实可行的和 cost-effective 的方法, 以确保适当的外科训练前植入微电极阵列在活体人类大脑皮层。
Introduction
近年来, 在活体脑中记录多个单个神经元活动的挑战的技术解决方案的发展1,2,3。硅基微电极阵列在信号特性方面与传统的线电极相似, 它们可以在脑组织的小片中记录几十到数百个神经元4,5,6,7. 微电极阵列使科学家们能够在猴子的初级运动皮层和手臂运动之间建立神经活动的对应关系,8, 这反过来又为脑机的发展提供了推动力。接口 (BCIs)9。
微电极阵列已被用于人类在两种情况下: 作为慢性植入物控制 BCIs 和作为 semi-chronic 植入物, 研究的活动的个别神经元的病人患有癫痫。慢性植入物, 以手的功能表示为目标在主要马达皮层, 允许患者遭受四肢控制机器人胳膊或计算机游标的运动10,11,12 ,13。半慢性植入物, 连同硬膜下脑电图 (ECOG) 电极插入与耐药癫痫患者谁是癫痫手术的候选者14, 允许单录音之前, 期间和之后癫痫发作,并已开始阐明癫痫发作期间和期间单个神经元的活动15,16,17,18,19。微电极阵列有可能显著提高我们对大脑功能的认识, 通过建立神经元活动之间的联系, 以及人类的感知、运动和思想, 无论是在健康方面还是在疾病, 在其他20,21。
硅基微电极阵列现已商业化, 其在人类中的使用已被美国的监管当局批准在 semi-chronic 癫痫征兆。然而, 这些设备是侵入性的, 必须插入到大脑中。不适当的插入技术的消极后果, 除了设备的失败记录神经元活动, 包括脑出血和感染, 潜在的长期或永久性的神经功能障碍。尽管目前尚不清楚微电极阵列植入术的并发症率, 但颅内脑电图 (EEG) macroelectrodes 的潜在严重并发症发生率为 1-5%22,23. 因此, 正确植入微电极阵列需要广泛的神经外科技术和特定的程序训练。
在安全的环境中, 外科医生用微电极阵列来磨练技能的方法包括非人类哺乳动物和人体尸体。理想的训练模式将忠实地再现人类头骨的大小和厚度;硬脑膜的韧性和血管衍生物;人脑的 gyrification 模式、一致性和脉动;循环血和脑脊液的存在;以及主体在手术室 (或) 类似环境中的整体定位。因此, 动物模型需要有足够的规模, 为外科医生提供有意义的经验。大型非人灵长类动物最接近, 但他们的外科训练的使用是不可持续的, 从伦理的角度来看, 因为它们是昂贵的。啮齿目动物不进入考虑由于他们的小大小;即使是猫或兔子, 也意味着从一个或类似的环境中明显地发散。
人类的尸体代表着一个诱人的选择他们的优势包括生命样的大小和头部和大脑的形状和在一个或类似的环境中建立外科训练的可能性。最明显的离开从现实的情况是没有脑脉动和出血, 并修改的方面和一致性的身体组织, 是专门为尸体保存的技术24。新鲜冷冻的尸体在某种程度上保持了许多器官和组织的一致性和灵活性, 但它们有几个缺点: 一旦解冻开始, 它们就开始降解, 从而使大脑变得过于退化, 无法插入微电极阵列要现实地执行, 它们是一种相对稀少且昂贵的资源。而甲醛固定的尸体, 另一方面, 是更实惠, 可用和更耐用, 以牺牲硬化组织的一致性。
在这里, 我们建立了一个程序使用甲醛固定的人体模型, 提供神经外科训练的植入皮层微电极阵列。我们的方法允许现实的, 或类似的定位和仪器;进行开颅和 durotomy, 暴露皮层表面;将电极基座连接到颅骨骨周围的开颅;用气动冲击器25将微电极阵列插入到大脑皮层中。重要的是, 它使外科医生能够实践的精确对准的微电极阵列 (这是连接到电极基座由一捆单独绝缘金丝) 平行的皮层表面26。我们的协议忠实地复制的迹象, 微电极阵列植入和 ECOG 植入的病人谁是癫痫手术的候选者。微电极阵列的精确类型对植入手术的特殊性有显著影响;在这里, 我们描述了一个数组的程序, 最近得到了在美国使用的监管批准。so-called 犹他阵列包括一个4×4 毫米, 100 微电极网格;附着在颅骨外表上的经皮底座;和连接两个的线束。
Protocol
Representative Results
Discussion
甲醛固定的人体尸体模型和手术协议描述复制的外科手术过程中植入微电极阵列到人脑皮质。该过程的每一步, 包括微电极阵列的定位和它的插入与气动插入, 进行几乎相同的方式在现实生活中的病人, 除了脑搏动和循环缺席。该协议中的关键步骤是将微电极阵列与皮层表面对齐, 并使用气动插入将其撞击到皮层。必须注意将该阵列近似为与皮质表面平行的可能性。在这种情况下, 该阵列不说谎冲洗…
Divulgazioni
The authors have nothing to disclose.
Acknowledgements
作者感谢 Dr. 罗布 (贝莱德微计算机系统), Prof. Margitta Seeck (神经内科, 日内瓦大学医院, 日内瓦, 瑞士), Dr. 安德烈巴托丽和 Prof. 卡尔夏勒 (日内瓦大学神经外科司医院, 日内瓦, 瑞士), 和 Mr. 马卢达 Burdin 和 Prof. 约翰 p o’donoghue (Wyss 中心为生物和神经, 日内瓦, 瑞士) 为他们的支持在准备当前工作。
Materials
| Mayfield skull clamp | Integra LifeSciences, Cincinnati, OH | A1059 | |
| Midas Rex MR7 system for craniotomy | Medtronic, Minneapolis, MN | EC300 | |
| Dura scissors | Sklar Surgical Instruments, West Chester, PA | 22-2742 | |
| Self-tapping bone screws | OrthoMed Inc., Tigard, OR | OM SYN211806 | |
| Microelectrode array and pedestal | Blackrock Microsystems, Salt Lake City, UT | LB-0612 | Mock-up arrays are available from the manufacturer upon request |
| Pneumatic impacter | Blackrock Microsystems, Salt Lake City, UT | LB-0088 | |
| 64-channel electrocorticography grid | Ad-Tech Medical Instrument Corporation, Racine, WI | FG64C-SP10X-0C6 | Optional |
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