Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics

电阻抗断层成像（EIT）是一种新型的医学成像方法，它独特地提供了一种成像方式， 使用外部电极阵列的神经组织中的神经元去极化。在老鼠的大脑皮层中， 分辨率<200µm和1 ms，在感觉诱发电位过程中使用上皮层电极阵列。已经 由伦敦UCL的PI大卫保持器开创，他最近将其扩展到成像复合动作电位 神经内的交通与灵活的硅橡胶圆柱形袖口。然后，相同的袖带也可以用于选择性地测量。 刺激所识别的神经束。这得到了Galvani Bioelectronics的支持，因为它可以提供 避免电刺激植物神经时产生脱靶效应的重要途径。到目前为止， 使用具有16-32个电极的外部圆柱形袖带进行。空间分辨率在边缘处良好， 在电极附近的神经，但减少对神经的中心，电流密度较小。我们的目标 是通过调整袖带以具有“侧手翻”设计来提高空间分辨率， 神经的内部。穿透性神经内电极是刚性的，并且会导致神经损伤、炎症和神经功能丧失。 记录能力。然而，我们通过使用co-PI开创的新型“形状记忆聚合物”来减轻这种风险。 德克萨斯大学达拉斯分校（UTD）的沃尔特·沃伊特。这在室温下是刚性的，因此允许插入，但是 在体温下变得柔软，因此它是生物相容的并且不会引起炎症反应。这 将允许成像中神经内部的更高空间分辨率，同时还提供了一种实现 单独使用外部圆柱形袖带不可能选择性刺激已识别的神经束。 在第一年，我们将对不同的电极材料进行初步研究， 4个辐条的几何形状，每个辐条具有4个电极。这将在盐水填充罐、绵羊迷走神经体外和体内进行测试， 兔坐骨神经在体。在第二年，进一步的急性研究，在兔坐骨神经和羊迷走神经诱发 活动将与改进的电极几何形状建议的建模和实证研究， 第1年，最多16个辐条，每个辐条有16个电极。在第3年，我们将评估生物相容性， 在长达3个月的绵羊迷走神经慢性研究和急性初步研究中的成像性能 受试者的人迷走神经，其中神经暴露以插入迷走神经刺激器。同时，我们 将优化EIT成像重建方法，将联合收割机EIT学术软件组合成一个强大的软件包， 用于临床试验，并开发可通过内窥镜插入的机械电极插入装置。 在所有动物研究中，将通过组织学、电生理学和EIT成像评估性能。 可交付成果将是一种新颖的“侧手翻”电极设计，用于神经中的高分辨率EIT成像， 严格评估其性能和生物相容性。我们认为它对神经的损伤可以忽略不计 当使用数月并在整个横截面上传递分支复合动作电位的成像时 对人体迷走神经的测量精度<150µm，1 ms。

Electrical Impedance Tomography (EIT) is a new medical imaging method which, uniquely, offers a way to image neuronal depolarization in nervous tissue using arrays of external electrodes. In rat cerebral cortex, it has a resolution of <200µm and 1 ms using epicortical electrode arrays during sensory evoked potentials. It has been pioneered by PI David Holder at UCL London who has recently extended it to imaging compound action potential traffic within nerves with a flexible silicone rubber cylindrical cuff. The same cuff may then also be used for selective stimulation of the identified fascicles. This has been supported by Galvani Bioelectronics as it could furnish an essential way to avoid off-target effects in Electroceutical stimulation of autonomic nerve. Until now, it has been undertaken using an external cylindrical cuff with 16-32 electrodes. Spatial resolution is good at the edge of the nerve near the electrodes but decreases towards the centre of the nerve where current density is less. Our objective is to improve spatial resolution by adapting the cuff to have a “cartwheel” design with spokes extending into the interior of the nerve. Penetrating intraneural electrodes are rigid and cause nerve damage, inflammation, and loss of recording ability. However, we mitigate this risk by the use of novel “shape memory polymer” pioneered by co-PI Walter Voit at University of Texas Dallas (UTD). This is rigid at room temperature, so permitting insertion, but becomes flexible at body temperature so that it is biocompatible and does not elicit an inflammatory response. This would permit higher spatial resolution in the interior of the nerve in imaging while also offering a way to achieve selective stimulation of identified fascicles impossible with an external cylindrical cuff alone. In year 1 we will undertake preliminary studies with different electrode materials and a preliminary geometry of 4 spokes with 4 electrodes each. This will be tested in saline filled tanks, sheep vagus ex and in vivo, and rabbit sciatic nerve in vivo. In Year 2, further acute studies in rabbit sciatic and sheep vagus nerve during evoked activity will be undertaken with an improved electrode geometry suggested by modelling and empirical studies in Year 1, with up to 16 spokes with 16 electrodes each. In Year 3, we will evaluate the biocompatibility and performance in imaging in chronic studies over up to 3 months in sheep vagus nerve and an acute pilot study in human vagus nerve in subjects where the nerve is exposed for insertion of a vagal nerve stimulator. In parallel, we will optimise EIT imaging reconstruction methods, combine EIT academic software into a robust package ready for use in clinical trials, and develop a mechanical electrode insertion rig which can be inserted through an endoscope. In all animal studies, performance will be assessed by histology, electrophysiology and EIT imaging. The deliverable will be a novel “cartwheel” electrode design for high resolution EIT imaging in nerve, and a rigorous evaluation of its performance and biocompatibility. We envisage that it will cause negligible nerve damage when used over months and deliver imaging of fascicular compound action potentials throughout the cross section of the nerve with an accuracy of <150µm and 1ms for human vagus nerve.