Objective. Understanding the coding of neural activity in nerve fascicles is a high priority in computational neuroscience, electroceutical autonomic nerve stimulation and functional electrical stimulation for treatment of paraplegia. Unfortunately, it has been little studied as no technique has yet been available to permit imaging of neuronal depolarization within fascicles in peripheral nerve. Approach. We report a novel method for achieving this, using a flexible cylindrical multi-electrode cuff placed around nerve and the new medical imaging technique of fast neural electrical impedance tomography (EIT). In the rat sciatic nerve, it was possible to distinguish separate fascicles activated in response to direct electrical stimulation of the posterior tibial and common peroneal nerves. Main results. Reconstructed EIT images of fascicular activation corresponded with high spatial accuracy to the appropriate fascicles apparent in histology, as well as the inverse source analysis (ISA) of compound action potentials (CAP). With this method, a temporal resolution of 0.3 ms and spatial resolution of less than 100 µm was achieved. Significance. The method presented here is a potential solution for imaging activity within peripheral nerves with high spatial accuracy. It also provides a basis for imaging and selective neuromodulation to be incorporated in a single implantable nonpenetrating peri-neural device.
Electrical Impedance Tomography (EIT) is a non-invasive imaging technique, which has the potential to expedite the differentiation of ischaemic or haemorrhagic stroke, decreasing the time to treatment. Whilst demonstrated in simulation, there are currently no suitable imaging or classification methods which can be successfully applied to human stroke data. Development of these complex methods is hindered by a lack of quality Multi-Frequency EIT (MFEIT) data. To address this, MFEIT data were collected from 23 stroke patients, and 10 healthy volunteers, as part of a clinical trial in collaboration with the Hyper Acute Stroke Unit (HASU) at University College London Hospital (UCLH). Data were collected at 17 frequencies between 5 Hz and 2 kHz, with 31 current injections, yielding 930 measurements at each frequency. This dataset is the most comprehensive of its kind and enables combined analysis of MFEIT, Electroencephalography (EEG) and Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) data in stroke patients, which can form the basis of future research into stroke classification.
Epilepsy affects approximately 50 million people worldwide, and 20–30% of these cases are refractory to antiepileptic drugs. Many patients with intractable epilepsy can benefit from surgical resection of the tissue generating the seizures; however, difficulty in precisely localising seizure foci has limited the number of patients undergoing surgery as well as potentially lowered its effectiveness. Here we demonstrate a novel imaging method for monitoring rapid changes in cerebral tissue impedance occurring during interictal and ictal activity, and show that it can reveal the propagation of pathological activity in the cortex. Cortical impedance was recorded simultaneously to ECoG using a 30-contact electrode mat placed on the exposed cortex of anaesthetised rats, in which interictal spikes (IISs) and seizures were induced by cortical injection of 4-aminopyridine (4-AP), picrotoxin or penicillin. We characterised the tissue impedance responses during IISs and seizures, and imaged these responses in the cortex using Electrical Impedance Tomography (EIT). We found a fast, transient drop in impedance occurring as early as 12 ms prior to the IISs, followed by a steep rise in impedance within ~ 120 ms of the IIS. EIT images of these impedance changes showed that they were co-localised and centred at a depth of 1 mm in the cortex, and that they closely followed the activity propagation observed in the surface ECoG signals. The fast, pre-IIS impedance drop most likely reflects synchronised depolarisation in a localised network of neurons, and the post-IIS impedance increase reflects the subsequent shrinkage of extracellular space caused by the intense activity. EIT could also be used to picture a steady rise in tissue impedance during seizure activity, which has been previously described. Thus, our results demonstrate that EIT can detect and localise different physiological changes during interictal and ictal activity and, in conjunction with ECoG, may in future improve the localisation of seizure foci in the clinical setting.
A highly versatile Electrical Impedance Tomography (EIT) system, nicknamed the ScouseTom, has been developed. The system allows control over current amplitude, frequency, number of electrodes, injection protocol and data processing. Current is injected using a Keithley 6221 current source, and voltages are recorded with a 24-bit EEG system with minimum bandwidth of 3.2 kHz. Custom PCBs interface with a PC to control the measurement process, electrode addressing and triggering of external stimuli. The performance of the system was characterised using resistor phantoms to represent human scalp recordings, with an SNR of 77.5 dB, stable across a four hour recording and 20 Hz to 20 kHz. In studies of both haeomorrhage using scalp electrodes, and evoked activity using epicortical electrode mats in rats, it was possible to reconstruct images matching established literature at known areas of onset. Data collected using scalp electrode in humans matched known tissue impedance spectra and was stable over frequency. The experimental procedure is software controlled and is readily adaptable to new paradigms. Where possible, commercial or open-source components were used, to minimise the complexity in reproduction. The hardware designs and software for the system have been released under an open source licence, encouraging contributions and allowing for rapid replication.
Electrical Impedance Tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of internal impedance changes within an object using non-penetrating surface electrodes. It has previously been used to image impedance changes due to neuronal depolarisation during evoked potentials in the rat somatosensory cortex with a resolution of 2 ms and <200 μm, using an epicortical electrode array. The purpose of this work was to use this technique to elucidate the intracortical spatiotemporal trajectory of ictal spike-and-wave discharges (SWDs), induced by electrical stimulation in an acute rat model of epilepsy, throughout the cerebral cortex. Seizures lasting 16.5 ± 5.3 s with repetitive 2–5 Hz SWDs were induced in five rats anaesthetised with fentanyl-isoflurane. Transfer impedance measurements were obtained during each seizure with a 57-electrode epicortical array by applying 50 μA current at 1.7 kHz to two electrodes and recording voltages from all remaining electrodes. Images were reconstructed from averaged SWD-related impedance traces obtained from EIT measurements in successive seizures. We report the occurrence of reproducible impedance changes during the initial spike phase, which had an early onset in the whisker barrel cortex and spread posteriorly, laterally and ventrally over 20 ms (p < 0.03125, N = 5). These findings, which confirm and extend knowledge of SWD initiation and expression, suggest that EIT is a valuable neuroimaging tool for improving understanding of neural circuits implicated in epileptic phenomena.
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