Nambiar Aparna, Nolta Nicholas F, Han Martin
Department of Biomedical Engineering, University of Connecticut, Storrs, CT, United States.
Front Neurosci. 2019 Apr 24;13:393. doi: 10.3389/fnins.2019.00393. eCollection 2019.
Extensive research using penetrating electrodes implanted in the central and peripheral nervous systems has been performed for many decades with significant advances made in recent years. While penetrating devices provide proximity to individual neurons , they suffer from declining performance over the course of months and often fail within a year. 2D histology studies using serial tissue sections have been extremely insightful in identifying and quantifying factors such as astroglial scar formation and neuronal death around the implant sites that may be contributing to failures. However, 2D histology has limitations in providing a holistic picture of the problems occurring at the electrode-tissue interface and struggles to analyze tissue below the electrode tips where the electrode tracks are no longer visible. In this study, we present 3D reconstruction of serial sections to overcome the limitations of 2D histological analysis. We used a cohort of software: XuvStitch, AutoAligner, and Imaris coupled with custom MATLAB programming to correct warping effects. Once the 3D image volume was reconstructed, we were able to use Imaris to quantify neuronal densities around the electrode tips of a hybrid microelectrode array incorporating Blackrock, Microprobes, and NeuroNexus electrodes in the same implant. This paper presents proof-of-concept and detailed methodological description of a technique which can be used to quantify neuronal densities in future studies of implanted electrodes.
几十年来，人们一直在使用植入中枢和周围神经系统的穿透性电极进行广泛研究，近年来取得了重大进展。虽然穿透性设备能够靠近单个神经元，但在数月的时间里其性能会逐渐下降，并且通常在一年内就会失效。使用连续组织切片进行的二维组织学研究在识别和量化诸如植入部位周围星形胶质瘢痕形成和神经元死亡等可能导致失效的因素方面极具洞察力。然而，二维组织学在全面呈现电极 - 组织界面出现的问题方面存在局限性，并且难以分析电极尖端下方不再可见电极轨迹的组织。在本研究中，我们展示了连续切片的三维重建，以克服二维组织学分析的局限性。我们使用了一组软件：XuvStitch、AutoAligner和Imaris，并结合定制的MATLAB编程来校正翘曲效应。一旦重建了三维图像体积，我们就能够使用Imaris来量化在同一植入物中包含Blackrock电极、Microprobes电极和NeuroNexus电极的混合微电极阵列电极尖端周围的神经元密度。本文展示了一种可用于在未来植入电极研究中量化神经元密度的技术的概念验证和详细方法描述。
