Development of polarization-sensitive optical coherence tomography imaging platform and metrics to quantify electrostimulation-induced peripheral nerve injury in vivo in a small animal model

Abstract

. Significance Neuromodulation devices are rapidly evolving for the treatment of neurological diseases and conditions. Injury from implantation or long-term use without obvious functional losses is often only detectable through terminal histology. New technologies are needed that assess the peripheral nervous system (PNS) under normal and diseased or injured conditions. Aim We aim to demonstrate an imaging and stimulation platform that can elucidate the biological mechanisms and impacts of neurostimulation in the PNS and apply it to the sciatic nerve to extract imaging metrics indicating electrical overstimulation. Approach A sciatic nerve injury model in a 15-rat cohort was observed using a newly developed imaging and stimulation platform that can detect electrical overstimulation effects with polarization-sensitive optical coherence tomography. The sciatic nerve was electrically stimulated using a custom-developed nerve holder with embedded electrodes for 1 h, followed by a 1-h recovery period, delivered at above-threshold Shannon model -values in experimental groups: sham control (SC, , ), stimulation level 1 (SL1, , , and ), and stimulation level 2 (SL2, , , and ). Results The stimulation and imaging system successfully captured study data across the cohort. When compared to a SC after a 1-week recovery, the fascicle closest to the stimulation lead showed an average change of (SL1/SL2) in phase retardation and in optical attenuation relative to SC. Analysis of immunohistochemistry (IHC) shows a difference in myelin pixel counts and difference in axon pixel counts, and an overall increase in cell nuclei pixel count of . These metrics were consistent with IHC and hematoxylin/eosin tissue section analysis. Conclusions The poststimulation changes observed in our study are manifestations of nerve injury and repair, specifically degeneration and angiogenesis. Optical imaging metrics quantify these processes and may help evaluate the safety and efficacy of neuromodulation devices.

Neurosurgical Intervention for Nerve and Muscle Biopsies

“…OCT uses low-coherence light to capture micrometer-resolution two-and three-dimensional images from within optical scattering media. Of note, this technique has been used in animal models to obtain high-resolution images of sciatic nerves, [128,129] to monitor microvasculature flow around peripheral nerves as they are electrically stimulated, [130,131] and to capture functional images of nerves [132]. The non-invasive nature of this technique makes biopsies of nerves possible without causing damage or impairing function, making studies such as those to visualize retinal nerve fibers in diabetic patients possible [133,134].…”

Neurosurgical Intervention for Nerve and Muscle Biopsies

“…OCT uses low-coherence light to capture micrometer-resolution two- and three-dimensional images from within optical scattering media. Of note, this technique has been used in animal models to obtain high-resolution images of sciatic nerves [ 126 , 127 ], to monitor microvasculature flow around peripheral nerves as they are electrically stimulated [ 128 , 129 ], and to capture functional images of nerves [ 130 ]. The non-invasive nature of this technique makes biopsies of nerves possible without causing damage or impairing function, making studies such as those to visualize retinal nerve fibers in diabetic patients possible [ 131 , 132 ].…”