Toward optical coherence tomography angiography-based biomarkers to assess the safety of peripheral nerve electrostimulation

OBJECTIVE. Peripheral nerves serve as a link between the central nervous system and its targets. Altering peripheral nerve activity through targeted electrical stimulation is being investigated as a therapy for modulating end organ function. To support rapid advancement in the field, novel approaches to predict and prevent nerve injury resulting from electrical stimulation must be developed to overcome the limitations of traditional histological methods. The present study aims to develop an optical imaging-based approach for real-time assessment of peripheral nerve injury associated with electrical stimulation. APPROACH. We developed an optical coherence tomography (OCT) angiography system and a 3D printed stimulating nerve stabilizer (sNS) to assess the real-time microvascular and blood flow changes associated with electrical stimulation of peripheral nerves. We then compared the microvascular changes with established nerve function analysis and immunohistochemistry to correlate changes with nerve injury. MAIN RESULTS. Electrical stimulation of peripheral nerves has a direct influence on vessel diameter and capillary flow. The stimulation used in this study did not alter motor function significantly, but a delayed onset of mechanical allodynia at lower thresholds was observed using a sensory function test. Immunohistochemical analysis pointed to an increased number of macrophages within nerve fascicles and axon sprouting potentially related to nerve injury. SIGNIFICANCE. This study is the first to demonstrate the ability to image peripheral nerve microvasculature changes during electrical stimulation. This expands the knowledge in the field and can be used to develop potential biomarkers to predict nerve injury resulting from electrical stimulation.