Characterizing the aging processes of electrodes in vivo is essential in order to elucidate the changes of the electrode–tissue interface and the device. However, commonly used impedance measurements at 1 kHz are insufficient for determining electrode viability, with measurements being prone to false positives. We implanted cohorts of five iridium oxide (IrOx) and six platinum (Pt) Utah arrays into the sciatic nerve of rats, and collected the electrochemical impedance spectroscopy (EIS) up to 12 weeks or until array failure. We developed a method to classify the shapes of the magnitude and phase spectra, and correlated the classifications to circuit models and electrochemical processes at the interface likely responsible. We found categories of EIS characteristic of iridium oxide tip metallization, platinum tip metallization, tip metal degradation, encapsulation degradation, and wire breakage in the lead. We also fitted the impedance spectra as features to a fine-Gaussian support vector machine (SVM) algorithm for both IrOx and Pt tipped arrays, with a prediction accuracy for categories of 95% and 99%, respectively. Together, this suggests that these simple and computationally efficient algorithms are sufficient to explain the majority of variance across a wide range of EIS data describing Utah arrays. These categories were assessed over time, providing insights into the degradation and failure mechanisms for both the electrode–tissue interface and wire bundle. Methods developed in this study will allow for a better understanding of how EIS can characterize the physical changes to electrodes in vivo.

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.