Investigating the safety of fast neural electrical impedance tomography in the rat brain

OBJECTIVE Electrical impedance tomography (EIT) can be used to image impedance changes which arise due to fast electrical activity during neuronal depolarisation and so holds therapeutic potential for improving the localisation of epileptic seizure foci in patients with treatment-resistant epilepsy to aid surgical resection of epileptogenic tissue. Prolonged cortical stimulation may, however, induce neural injury through excitotoxicity and electrochemical reactions at the tissue-electrode interface. The purpose of this work was to assess whether current levels used in fast neural EIT studies induce histologically detectable tissue damage when applied continuously to the rat cerebral cortex. APPROACH A 57-electrode epicortical array was placed on one or both hemispheres of adult Sprague Dawley rats anaesthetised with isoflurane. In an initial series of experiments, current was injected simultaneously at 10, 25, 50, 75 and 100 µA for 1 h at 1.725 kHz through five electrodes across two epicortical arrays to provide a preliminary indication of the safety of these current levels. Since no obvious cortical damage was observed in these rats, the current level chosen for further investigation was 100 µA, the upper-bound of the range of interest. In a separate series of experiments, 100 µA was applied through a single electrode for 1 h at 1.725 kHz to verify its safety. Following termination of stimulation, brain samples were fixed in formalin and histologically processed with Haematoxylin and Eosin (H&E) and Nissl stains. MAIN RESULTS Histological analysis revealed that continuous injection of 100 µA current, equating to a current density of 354 Am-2, into the rat cortex at 1.725 kHz does not cause cortical tissue damage or any alterations to neuronal morphology. SIGNIFICANCE The safety of current injections during typical EIT protocols for imaging fast neural activity have been validated. The current density established to be safe for continuous application to the cortex, 354 Am-2, exceeds the present safety limit of 250 Am-2 which has been complied with to date, and thus encourages the application of more intensified fast neural EIT protocols. These findings will aid protocol design for future clinical and in vivo EIT investigations aimed at imaging fast neural activity, particularly in situations where the signal-to-noise ratio is considerably reduced.