Highlights The vagus nerve provides innervation to the majority of the visceral organs. There is a need to delineate fascicular anatomy to avoid off-target effects of VNS. Neuronal tracing is a powerful tool to study fascicular organization.

Objective: The main objective of this study was to investigate which injection pattern led to the best imaging of fascicular compound activity in fast neural EIT of peripheral nerve using an external cylindrical 2  ×  14-electrodes cuff. Specifically, the study addressed the identification of the optimal injection pattern and of the optimal region of the reconstructed volume to image fascicles. Approach: The effect of three different measurement protocol features (transversal/longitudinal injection, drive electrode spacing, referencing configuration) over imaging was investigated in simulation with the use of realistic impedance changes and noise levels. Image-based metrics were employed to evaluate the quality of the reconstructions over the reconstruction domain. The optimal electrode addressing protocol suggested by the simulations was validated in vivo on the tibial and peroneal fascicles of rat sciatic peripheral nerves (N  =  3) against MicroCT reference images. Main results: Injecting current transversally, with spacing of  ⩾4 electrodes apart (⩾100°) and single-ring referencing of measurements, led to the best overall localization when reconstructing on the edge of the electrode array closest to the reference. Longitudinal injection protocols led to a higher SNR of the reconstructed image but poorer localization. All in vivo EIT recordings had statistically significant impedance variations (p   <  0.05). Overall, fascicle center-of-mass (CoM) localization error was estimated at 141  ±  56 µm (−26  ±  94 µm and 5  ±  29° in radial coordinates). Significant difference was found (p   <  0.05) between mean angular location of the tibial and peroneal CoMs. Significance: This study gives the reader recommendations for performing fast neural EIT of fascicular compound activity using the most effective protocol features.

Imaging compound action potentials (CAPs) in peripheral nerves could help avoid side effects in neuromodulation by selective stimulation of identified fascicles. Existing methods have low resolution, limited imaging depth, or are invasive. Fast neural electrical impedance tomography (EIT) allows fascicular CAP imaging with a resolution of <200 µm, <1 ms using a non-penetrating flexible nerve cuff electrode array. Here, we validate EIT imaging in rat sciatic nerve by comparison to micro-computed tomography (microCT) and histology with fluorescent dextran tracers. With EIT, there are reproducible localized changes in tissue impedance in response to stimulation of individual fascicles (tibial, peroneal and sural). The reconstructed EIT images correspond to microCT scans and histology, with significant separation between the fascicles (p < 0.01). The mean fascicle position is identified with an accuracy of 6% of nerve diameter. This suggests fast neural EIT can reliably image the functional fascicular anatomy of the nerves and so aid selective neuromodulation.

The functional anatomy of fascicles evident in human and large mammal cervical vagus nerve is unknown. Organ-specific organization in the pig cervical nerve has been observed for cardiac, recurrent laryngeal and pulmonary function using anatomical tracing with X-ray microCT, and functional connectivity with selective stimulation or fast neural Electrical Impedance Tomography (EIT) with a custom nerve cuff. Electrical stimulation of the vagus nerve (VNS) is currently used to treat drug-resistant epilepsy and depression but current practice of stimulation of the entire nerve causes undesired side effects. These findings pave the way for improved outcomes in VNS as unwanted side effects could be reduced by targeted selective stimulation of identified organ-specific fascicles.

Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury. It is induced by sepsis, aspiration, and pneumonia, including that caused by SARS coronavirus and human influenza viruses. The main pathophysiological mechanism of ARDS is a systemic inflammatory response. Vagus nerve stimulation (VNS) can limit cytokine production in the spleen and thereby dampen any systemic inflammation and inflammation-induced tissue damage in the lungs and other organs. However, the effects of increased parasympathetic outflow to the lungs when non-selective VNS is applied may result in bronchoconstriction, increased mucus secretion and enhance local pulmonary inflammatory activity; this may outweigh the beneficial systemic anti-inflammatory action of VNS. Organ/function-specific therapy can be achieved by imaging of localized fascicle activity within the vagus nerve and selective stimulation of identified organ-specific fascicles. This may be able to provide selective neuromodulation of different pathways within the vagus nerve and offer a novel means to improve outcome in ARDS. This has motivated this review in which we discuss the mechanisms of anti-inflammatory effects of VNS, progress in selective VNS techniques, and a possible application for ARDS.