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

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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.