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研究快速神经电阻抗断层成像技术在大鼠脑部的安全性。

Investigating the safety of fast neural electrical impedance tomography in the rat brain.

机构信息

Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom.

出版信息

Physiol Meas. 2019 Apr 3;40(3):034003. doi: 10.1088/1361-6579/ab0d53.

Abstract

OBJECTIVE

Electrical impedance tomography (EIT) can be used to image impedance changes which arise due to fast electrical activity during neuronal depolarisation and so holds therapeutic potential for improving the localisation of epileptic seizure foci in patients with treatment-resistant epilepsy to aid surgical resection of epileptogenic tissue. Prolonged cortical stimulation may, however, induce neural injury through excitotoxicity and electrochemical reactions at the tissue-electrode interface. The purpose of this work was to assess whether current levels used in fast neural EIT studies induce histologically detectable tissue damage when applied continuously to the rat cerebral cortex.

APPROACH

A 57-electrode epicortical array was placed on one or both hemispheres of adult Sprague Dawley rats anaesthetised with isoflurane. In an initial series of experiments, current was injected simultaneously at 10, 25, 50, 75 and 100 µA for 1 h at 1.725 kHz through five electrodes across two epicortical arrays to provide a preliminary indication of the safety of these current levels. Since no obvious cortical damage was observed in these rats, the current level chosen for further investigation was 100 µA, the upper-bound of the range of interest. In a separate series of experiments, 100 µA was applied through a single electrode for 1 h at 1.725 kHz to verify its safety. Following termination of stimulation, brain samples were fixed in formalin and histologically processed with Haematoxylin and Eosin (H&E) and Nissl stains.

MAIN RESULTS

Histological analysis revealed that continuous injection of 100 µA current, equating to a current density of 354 Am, into the rat cortex at 1.725 kHz does not cause cortical tissue damage or any alterations to neuronal morphology.

SIGNIFICANCE

The safety of current injections during typical EIT protocols for imaging fast neural activity have been validated. The current density established to be safe for continuous application to the cortex, 354 Am, exceeds the present safety limit of 250 Am which has been complied with to date, and thus encourages the application of more intensified fast neural EIT protocols. These findings will aid protocol design for future clinical and in vivo EIT investigations aimed at imaging fast neural activity, particularly in situations where the signal-to-noise ratio is considerably reduced.

摘要

目的

电阻抗断层成像(EIT)可用于成像神经元去极化时快速电活动引起的阻抗变化,因此具有改善耐药性癫痫患者癫痫灶定位的治疗潜力,以帮助切除致痫组织。然而,长时间皮质刺激可能通过兴奋毒性和组织-电极界面的电化学反应引起神经损伤。这项工作的目的是评估在快速神经 EIT 研究中使用的电流水平在连续施加于大鼠大脑皮层时是否会引起组织学上可检测到的损伤。

方法

将 57 个电极的皮层外电极阵列放置在异氟烷麻醉的成年 Sprague Dawley 大鼠的一侧或两侧半球上。在一系列初始实验中,通过两个皮层外电极阵列中的五个电极同时以 10、25、50、75 和 100µA 的电流注入 1 小时,频率为 1.725kHz,以初步确定这些电流水平的安全性。由于在这些大鼠中没有观察到明显的皮质损伤,因此选择 100µA 作为进一步研究的电流水平,这是感兴趣的范围的上限。在另一系列实验中,通过单个电极以 1.725kHz 的频率应用 100µA 电流 1 小时,以验证其安全性。刺激终止后,将脑样本用福尔马林固定,并通过苏木精和伊红(H&E)和尼氏染色进行组织学处理。

主要结果

组织学分析显示,以 1.725kHz 的频率将 100µA 电流连续注入大鼠皮层,相当于电流密度为 354Am,不会引起皮质组织损伤或神经元形态的任何改变。

意义

已经验证了用于成像快速神经活动的典型 EIT 协议中电流注入的安全性。确定为安全连续应用于皮层的电流密度为 354Am,超过了迄今为止遵守的 250Am 的当前安全限制,因此鼓励应用更强化的快速神经 EIT 协议。这些发现将有助于未来旨在成像快速神经活动的临床和体内 EIT 研究的方案设计,特别是在信噪比大大降低的情况下。

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