Abstract
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.
Highlights
Recent developments in Electrical Impedance Tomography (EIT) have enabled imaging of the impedance changes which arise during fast electrical activity during neuronal depolarisation in somatosensory evoked potentials (SEPs) and epileptiform events at a high spatiotemporal resolution (Aristovich, et al, 2014; Aristovich, et al, 2016; Hannan, et al, 2018)
It was clear that the possibility of mechanical damage occurring in cortical tissue subjacent to electrode sites, albeit small, could not be dismissed but that this mechanical damage differed in appearance to that induced by electrical stimulation (Fig. 4)
Since our aim was to determine the safety of injecting alternating current (AC) itself into the cerebral cortex, addressing these issues would have complicated the evaluation of cortical damage induced exclusively by electrical stimulation and was beyond the scope of this work
Summary
EIT, holds therapeutic potential for improving the localisation of epileptic seizure foci in patients with treatment-resistant epilepsy to aid surgical resection of epileptogenic tissue (Fabrizi, et al, 2006) In these individuals, intracranial electrode mats are often placed on the cortical surface as part of an extensive presurgical evaluation comprising video-EEG telemetry to localise the epileptogenic zone and determine the likelihood of performing a successful surgery with minimal functional deficits (Duncan, 2011). Intracranial electrode mats are often placed on the cortical surface as part of an extensive presurgical evaluation comprising video-EEG telemetry to localise the epileptogenic zone and determine the likelihood of performing a successful surgery with minimal functional deficits (Duncan, 2011) In conjunction with these conventional methods, fast neural EIT may be performed by injecting current through electrode pairs on these intracranial mats, sequentially or in parallel, and recording the resulting boundary voltages from all remaining electrodes (Dowrick, et al, 2015). Of equal importance is the need to avoid significant current-induced influences on neuronal excitability, those that result in irreversible structural damage
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