Toward Safety Protocols for Peripheral Nerve Stimulation (PNS): A Computational and Experimental Approach.

As the clinical applicability of peripheral nerve stimulation (PNS) expands, the need for PNS-specific safety criteria becomes pressing. This study addresses this need, utilizing a novel machine learning and computational bio-electromagnetics modeling platform to establish a safety criterion that captures the effects of fields and currents induced on axons. Our approach is comprised of three steps: experimentation, model creation, and predictive simulation. We collected high-resolution images of control and stimulated rat sciatic nerve samples at varying stimulation intensities and performed high-resolution image segmentation. These segmented images were used to train machine learning tools for the automatic classification of morphological properties of control and stimulated PNS nerves. Concurrently, we utilized our quasi-static Admittance Method-NEURON (AM-NEURON) computational platform to create realistic nerve models and calculate induced currents and charges, both critical elements of nerve safety criteria. These steps culminate in a cellular-level correlation between morphological changes and electrical stimulation parameters. This correlation informs the determination of thresholds of electrical parameters that are found to be associated with damage, such as maximum cell charge density. The proposed methodology and resulting criteria combine experimental findings with computational modeling to generate a safety threshold curve that captures the relationship between stimulation current and the potential for axonal damage. Although focused on a specific exposure condition, the approach presented here marks a step towards developing context-specific safety criteria in PNS neurostimulation, encouraging similar analyses across varied neurostimulation scenarios. Bioelectromagnetics.