Abstract
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.
Highlights
Imaging compound action potentials (CAPs) in peripheral nerves could help avoid side effects in neuromodulation by selective stimulation of identified fascicles
We present the first study in which the final optimized method was independently validated against histology with fluorescent dextran neural tracers and micro-computed tomography (microCT)
The duration above 30% of peak impedance change was 0.7 ± 0.3, 0.8 ± 0.3, and 0.8 ± 0.3 ms for each fascicle, respectively, as above, and each corresponded to the peak-evoked CAP measured on the same electrode
Summary
Imaging compound action potentials (CAPs) in peripheral nerves could help avoid side effects in neuromodulation by selective stimulation of identified fascicles. Histological examination after appropriate staining may be used to study the microanatomy of tissues and trace functional connections of nerve fascicles to their end organs[8] It requires fixation of the tissue, staining and microscopy with computerized tracking of numerous serial sections. Its clinical utility has been demonstrated for monitoring lung function[18], and research is in progress into its potential use in breast cancer[19], stroke[20,21], and detection of epileptic seizure onset zones[22] It can serve as a means to produce high-resolution tomographic images of activity in excitable neural tissue in brain and nerve with a millisecond and submillimeter resolution, “fast neural EIT.”. This produces a decrease in the bulk electrical impedance of ~0.1% during neuronal depolarization, which allows the applied EIT current to pass into the intracellular space, whereas at rest the EIT current predominantly travels in the extracellular space[17]
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