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)是一种新的医学成像方法，它独特地提供了一种使用外部电极阵列来成像神经组织中神经元去极化的方法。在大鼠大脑皮层，在感觉诱发电位过程中使用皮层电极阵列，分辨率为&lt；200微米和1毫秒。它由伦敦大学学院的Pi David Holder首创，他最近将其扩展到使用灵活的硅橡胶圆柱形袖带对神经内的复合动作电位交通进行成像。然后，相同的袖带也可用于选择性刺激所识别的束束。这一点得到了Galvani BioElectronics的支持，因为它可以提供一种必要的方法来避免自主神经电刺激中的脱靶效应。概念验证已经在大鼠坐骨神经中建立--它可以以200微米和1毫秒的分辨率成像腓骨、胫骨和腓肠束的复合动作电位活动。本项目旨在评估其在猪和人的自主神经成像和选择性刺激中的应用。目前，在组织学或人类颈迷走神经上发现的束束的功能解剖尚不清楚。这项工作的目的是1)制作颈部迷走神经束与胸腹部支配器官的连接图谱，以及2)确定选择性刺激EIT神经袖带的聚焦电流是否可以改变心脏和胃的功能。EIT系统和神经袖带将提供给3个美国小组，研究心脏、胃功能和其他自主神经功能的神经调节。首先，EIT成像将在生理激活最多10个器官的过程中进行，包括心脏、肺、喉和胃，已知这些器官由颈部迷走神经支配，以确定连接是否为器质性连接。其次，使用神经袖带进行选择性刺激。结果将通过与死后神经组织学神经示踪剂和3D Micro-CT示踪的金标准进行比较来验证。其成果将是阐明颈迷走神经中神经束的功能联系，并通过实验证实有可能选择性地刺激已识别的神经束并避免非靶点效应。后续研究将重现伦敦大学学院对植入迷走神经刺激器治疗癫痫的患者进行的人类研究结果，并评估其对心力衰竭或胃淤滞等疾病的益处。

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. Proof of concept has been established in rat sciatic nerve – it was possible to image compound action potential activity in the peroneal tibial and sural fascicles with a resolution of <200µm and 1 msec. This project is to evaluate its use in imaging and selective stimulation in autonomic nerves in pig and human studies. At present, the functional anatomy of fascicles evident on histology or the human cervical vagus nerve is unknown. The purpose of this work is 1) to produce an atlas of connections from fascicles in the cervical vagus nerve to organs innervated in the chest and abdomen and 2) To determine if function of the heart and stomach can be modified by selective stimulation of focused current from the EIT nerve cuff. EIT systems and nerve cuffs will be provided to 3 US groups working with anesthetized pig models on neuromodulation in cardiac, gastric function and other autonomic function. First, EIT imaging will be undertaken during physiological activation of up to 10 organs, including heart, lungs, larynx and stomach, known to be innervated by the cervical vagus nerve to ascertain if connections are organotopic. Secondly, selective stimulation will then be undertaken using the nerve cuffs. Results will be validated by comparison with the gold standards of post-mortem nerve histology with neural tracers and 3D micro-CT tracing. The deliverables will be elucidation of functional connections of fascicles in the cervical vagus nerve, and experimental confirmation that it is possible to stimulate identified fascicles selectively and avoid off-target effects. Follow-on studies will be to reproduce the findings in human studies at UCL in patients undergoing implantation of vagal nerve stimulators for epilepsy treatment, and evaluation of the benefits in diseases such as heart failure or gastric stasis.