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

通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描，增强多束周围神经复合动作电位的定量成像

• 批准号: 10009724
• 负责人: DAVID S HOLDER
• 金额: $ 57.49万
• 依托单位: UNIVERSITY COLLEGE LONDON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-07 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10009724
• 关键词: 3-Dimensional; Action Potentials; Acute; Address; Algorithms; Animals; Arthritis; Asthma; Benchmarking; Body Temperature; Caliber; Cardiac; Cerebral cortex; Cervical; Charge; Chronic; Clinical Research; Clinical Trials; Computer software; Development; Electric Stimulation; Electrodes; Electrophysiology (science); Endoscopes; Engineering; Epilepsy; Evaluation; Evoked Potentials; Fascicle; Fiber; Geometry; Heart; Histology; Human; Hypertension; Image; Image Analysis; Imaging Techniques; Inflammation; Inflammatory Response; Injections; Laparoscopes; London; Lung; Magnetic Resonance Imaging; Mechanics; Medical Imaging; Memory; Methods; Modeling; Nerve; Nerve Fibers; Nerve Tissue; Neurons; Organ; Oryctolagus cuniculus; Penetration; Performance; Peripheral Nerves; Peripheral Nervous System; Phase; Pilot Projects; Polymers; Positron-Emission Tomography; Radioisotopes; Rattus; Resolution; Risk; Safety; Saline; Sampling; Sensory; Shapes; Sheep; Silicone Elastomers; Specificity; Stomach; Surgeon; Techniques; Temperature; Testing; Texas; Time; TimeLine; Tissues; Training; Universities; Vagus nerve structure; autonomic nerve; base; biomaterial compatibility; density; design; electrical impedance tomography; flexibility; image reconstruction; imaging modality; improved; in vivo; interest; millisecond; minimally invasive; new technology; novel; quantitative imaging; reconstruction; relating to nervous system; sciatic nerve; side effect; single photon emission computed tomography; temporal measurement; user-friendly

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.

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的神经元去极化的方法。在大鼠大脑皮层中，在感觉诱发电位期间使用上皮层电极阵列，其分辨率<200µm和1 ms。它是由伦敦大学学院伦敦的PI大卫保持器开创的，他最近将其扩展到使用柔性硅橡胶圆柱形袖带成像神经内的复合动作电位交通。然后，相同的袖带也可以用于所识别的神经束的选择性刺激。这得到了Galvani Bioelectronics的支持，因为它可以提供一种避免自主神经电刺激中脱靶效应的基本方法。已在大鼠坐骨神经中建立了概念验证-可以以<200µm和1 msec的分辨率对腓胫束和腓肠束中的复合动作电位活动进行成像。本项目旨在评估其在猪和人体研究中用于自主神经成像和选择性刺激的用途。目前，在组织学或人类颈迷走神经上明显的神经束的功能解剖尚不清楚。这项工作的目的是1）产生从颈部迷走神经中的神经束到胸部和腹部受神经支配的器官的连接的图谱，以及2）确定是否可以通过选择性刺激来自EIT神经袖带的聚焦电流来改变心脏和胃的功能。EIT系统和神经袖带将提供给使用麻醉猪模型进行心脏、胃功能和其他自主神经功能神经调节的3个美国小组。首先，EIT成像将在多达10个器官的生理激活期间进行，包括已知由颈部迷走神经支配的心脏、肺、喉和胃，以确定连接是否是器官定位的。其次，选择性刺激，然后将进行使用神经袖口。将通过与死后神经组织学的金标准（神经示踪剂和3D micro-CT示踪）进行比较来验证结果。可交付成果将阐明颈部迷走神经中神经束的功能连接，并通过实验确认可以选择性刺激已识别的神经束并避免脱靶效应。后续研究将重现UCL在接受迷走神经刺激器植入治疗癫痫的患者中进行的人体研究的结果，并评价心力衰竭或胃郁积等疾病的获益。