Fast Neural Electrical Impedance Tomography Research Articles

Organotopic organization of the porcine mid-cervical vagus nerve.

Despite detailed characterization of fascicular organization of somatic nerves, the functional anatomy of fascicles evident in human and large mammal cervical vagus nerve is unknown. The vagus nerve is a prime target for intervention in the field of electroceuticals due to its extensive distribution to the heart, larynx, lungs, and abdominal viscera. However, current practice of the approved vagus nerve stimulation (VNS) technique is to stimulate the entire nerve. This produces indiscriminate stimulation of non-targeted effectors and undesired side effects. Selective neuromodulation is now a possibility with a spatially-selective vagal nerve cuff. However, this requires the knowledge of the fascicular organization at the level of cuff placement to inform selectivity of only the desired target organ or function. We imaged function over milliseconds with fast neural electrical impedance tomography and selective stimulation, and found consistent spatially separated regions within the nerve correlating with the three fascicular groups of interest, suggesting organotopy. This was independently verified with structural imaging by tracing anatomical connections from the end organ with microCT and the development of an anatomical map of the vagus nerve. This confirmed organotopic organization. Here we show, for the first time, localized fascicles in the porcine cervical vagus nerve which map to cardiac, pulmonary and recurrent laryngeal function (N = 4). These findings pave the way for improved outcomes in VNS as unwanted side effects could be reduced by targeted selective stimulation of identified organ-specific fiber-containing fascicles and the extension of this technique clinically beyond the currently approved disorders to treat heart failure, chronic inflammatory disorders, and more.

A combined cuff electrode array for organ-specific selective stimulation of vagus nerve enabled by Electrical Impedance Tomography.

Previously developed spatially-selective Vagus Nerve Stimulation (sVNS) allows the targeting of specific nerve fascicles through current steering in a multi-electrode nerve cuff but relies on a trial-and-error strategy to identify the relative orientation between electrodes and fascicles. Fast Neural Electrical Impedance Tomography (FN-EIT) has been recently used for imaging neural traffic in the vagus nerves of pigs in a cross-correlation study with sVNS and MicroCT fascicle tracking. FN-EIT has the potential for allowing targeted sVNS; however, up to now, stimulation and imaging have been performed with separate electrode arrays. In this study, different options were evaluated in-silico to integrate EIT and stimulation into a single electrode array without affecting spatial selectivity. The original pig vagus EIT electrode array geometry was compared with a geometry integrating sVNS and EIT electrodes, and with direct use of sVNS electrodes for EIT imaging. Modelling results indicated that both new designs could achieve image quality similar to the original electrode geometry in all tested markers (e.g., co-localisation error <100 µm). The sVNS array was considered to be the simplest due to the lower number of electrodes. Experimental results from testing evoked EIT imaging of recurrent laryngeal activity using electrodes from the sVNS cuff returned a signal-to-noise ratio similar to our previous study (3.9 ± 2.4 vs. 4.1 ± 1.5, N = 4 nerves from 3 pigs) and a lower co-localisation error (≈14% nerve diameter vs. ≈25%, N = 2 nerves from 2 pigs). Performing FN-EIT and sVNS on the same nerve cuff will facilitate translation to humans, simplify surgery and enable targeted neuromodulation strategies.

A 16-Channel Impedance-Readout IC With Synchronous Sampling and Baseline Cancelation for Fast Neural Electrical Impedance Tomography

Fast neural electrical impedance tomography (EIT) is a promising method to not only record neural activities but also to localize them in peripheral nerves in a minimally invasive way. A much higher image frame rate is required for this application than conventional impedance measurement applications, which generally adopt the I/Q demodulation technique. To achieve a high enough frame rate to capture neural activities along the peripheral nerve fascicle, this paper proposes synchronous sampling (SS) and fast baseline tracking based on successive approximation (SA). The SS method needs an injection of only a single or a few periods of square-wave current signal for the amplitude measurement by synchronously sampling the received voltage signal. The proposed SA-based baseline tracking provides fast signal recovery from unwanted motion artifacts or baseline drifts. The designed readout circuit uses a two-step conversion where its coarse bits are generated from a current-based baseline cancellation circuit and its fine bits from a following SAR ADC. Thanks to the baseline tracking based on the SS and SA, the proposed IC achieves a faster frame rate of 312 fps with continuous baseline update and 500 fps with constant baseline compared to state-of-the-art works. The implemented IC is validated by measuring a water-filled tank and reconstructing its tomographic image. The results show successful discrimination of varied impedance areas over the tank.

Overcoming temporal dispersion for measurement of activity-related impedance changes in unmyelinated nerves

Objective. Fast neural electrical impedance tomography is an imaging technique that has been successful in visualising electrically evoked activity of myelinated fibres in peripheral nerves by measurement of the impedance changes (dZ) accompanying excitation. However, imaging of unmyelinated fibres is challenging due to temporal dispersion (TP) which occurs due to variability in conduction velocities of the fibres and leads to a decrease of the signal below the noise with distance from the stimulus. To overcome TP and allow electrical impedance tomography imaging in unmyelinated nerves, a new experimental and signal processing paradigm is required allowing dZ measurement further from the site of stimulation than compound neural activity is visible. The development of such a paradigm was the main objective of this study. Approach. A finite element-based statistical model of TP in porcine subdiaphragmatic nerve was developed and experimentally validated ex-vivo. Two paradigms for nerve stimulation and processing of the resulting data—continuous stimulation and trains of stimuli, were implemented; the optimal paradigm for recording dispersed dZ in unmyelinated nerves was determined. Main results. While continuous stimulation and coherent spikes averaging led to higher signal-to-noise ratios (SNRs) at close distances from the stimulus, stimulation by trains was more consistent across distances and allowed dZ measurement at up to 15 cm from the stimulus (SNR = 1.8 ± 0.8) if averaged for 30 min. Significance. The study develops a method that for the first time allows measurement of dZ in unmyelinated nerves in simulation and experiment, at the distances where compound action potentials are fully dispersed.

Simplifying the hardware requirements for fast neural EIT of peripheral nerves

Objective. The main objective of this study was to assess the feasibility of lowering the hardware requirements for fast neural electrical impedance tomography (EIT) in order to support the distribution of this technique. Specifically, the feasibility of replacing the commercial modules present in the existing high-end setup with compact and cheap customized circuitry was assessed. Approach. Nerve EIT imaging was performed on rat sciatic nerves with both our standard ScouseTom setup and a customized version in which commercial benchtop current sources were replaced by custom circuitry. Electrophysiological data and images collected in the same experimental conditions with the two setups were compared. Data from the customized setup was subject to a down-sampling analysis to simulate the use of a recording module with lower specifications. Main results. Compound action potentials (573 ± 287 μV and 487 ± 279 μV, p=0.28) and impedance changes (36 ± 14 μV and 31 ± 16 μV, p=0.49) did not differ significantly when measured using commercial high-end current sources or our custom circuitry, respectively. Images reconstructed from both setups showed neglibile (<1voxel, i.e. 40 μm) difference in peak location and a high degree of correlation (R 2 = 0.97). When down-sampling from 24 to 16 bits ADC resolution and from 100 to 50 KHz sampling frequency, signal-to-noise ratio showed acceptable decrease (<−20%), and no meaningful image quality loss was detected (peak location difference <1voxel, pixel-by-pixel correlation R 2 = 0.99). Significance: The technology developed for this study greatly reduces the cost and size of a fast neural EIT setup without impacting quality and thus promotes the adoption of this technique by the neuroscience research community.

Fascicle localisation within peripheral nerves through evoked activity recordings: A comparison between electrical impedance tomography and multi-electrode arrays

BackgroundThe lack of understanding of fascicular organisation in peripheral nerves limits the potential of vagus nerve stimulation therapy. Two promising methods may be employed to identify the functional anatomy of fascicles within the nerve: fast neural electrical impedance tomography (EIT), and penetrating multi-electrode arrays (MEA). These could provide a means to image the compound action potential within fascicles in the nerve. New methodWe compared the ability to localise fascicle activity between silicon shanks (SS) and carbon fibre (CF) multi-electrode arrays and fast neural EIT, with micro-computed tomography (MicroCT) as an independent reference. Fast neural EIT in peripheral nerves was only recently developed and MEA technology has been used only sparingly in nerves and not for source localisation. Assessment was performed in rat sciatic nerves while evoking neural activity in the tibial and peroneal fascicles. ResultsRecorded compound action potentials were larger with CF compared to SS (∼700 μV vs ∼300 μV); however, background noise was greater (6.3 μV vs 1.7 μV) leading to lower SNR. Maximum spatial discrimination between Centres-of-Mass of fascicular activity was achieved by fast neural EIT (402 ± 30 μm) and CF MEA (414 ± 123 μm), with no statistical difference between MicroCT (625 ± 17 μm) and CF (p > 0.05) and between CF and EIT (p > 0.05). Compared to CF MEAs, SS MEAs had a lower discrimination power (103 ± 51 μm, p < 0.05). Comparison with existing methodsEIT and CF MEAs showed localisation power closest to MicroCT. Silicon MEAs adopted in this study failed to discriminate fascicle location. Re-design of probe geometry may improve results. ConclusionsNerve EIT is an accurate tool for assessment of fascicular position within nerves. Accuracy of EIT and CF MEA is similar to the reference method. We give technical recommendations for performing multi-electrode recordings in nerves.

Imaging slow brain activity during neocortical and hippocampal epileptiform events with electrical impedance tomography

Objective. Electrical impedance tomography (EIT) is an imaging technique that produces tomographic images of internal impedance changes within an object using surface electrodes. It can be used to image the slow increase in cerebral tissue impedance that occurs over seconds during epileptic seizures, which is attributed to cell swelling due to disturbances in ion homeostasis following hypersynchronous neuronal firing and its associated metabolic demands. In this study, we characterised and imaged this slow impedance response during neocortical and hippocampal epileptiform events in the rat brain and evaluated its relationship to the underlying neural activity. Approach. Neocortical or hippocampal seizures, comprising repeatable series of high-amplitude ictal spikes, were induced by electrically stimulating the sensorimotor cortex or perforant path of rats anaesthetised with fentanyl-isoflurane. Transfer impedances were measured during ≥30 consecutive seizures, by applying a sinusoidal current through independent electrode pairs on an epicortical array, and combined to generate an EIT image of slow activity. Main results. The slow impedance responses were consistently time-matched to the end of seizures and EIT images of this activity were reconstructed reproducibly in all animals (p < 0.03125, N = 5). These displayed foci of activity that were spatially confined to the facial somatosensory cortex and dentate gyrus for neocortical and hippocampal seizures, respectively, and encompassed a larger volume as the seizure progressed. Centre-of-mass analysis of reconstructions revealed that this activity corresponded to the true location of the epileptogenic zone, as determined by EEG recordings and fast neural EIT measurements which were obtained simultaneously. Significance. These findings suggest that the slow impedance response presents a reliable marker of hypersynchronous neuronal activity during epileptic seizures and can thus be utilised for investigating the mechanisms of epileptogenesis in vivo and for aiding localisation of the epileptogenic zone during presurgical evaluation of patients with refractory epilepsies.

Imaging fascicular organization of rat sciatic nerves with fast neural electrical impedance tomography

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.

SPARC: Method for Overcoming Temporal Dispersion in Unmyelinated Nerves for Imaging C Fibres with Electrical Impedance Tomography (EIT)

Fast neural EIT is a novel technique that enables imaging of evoked myelinated fibre activity in fascicles in rat sciatic nerve in vivo. However, imaging unmyelinated fibres is challenging due to temporal dispersion of the neural activity, caused by variability in fibre conduction velocities. This reduces the signal to below noise several centimetres from onset. The purpose of this work was to develop a method to overcome dispersion and allow EIT recordings of phasic activity at any distance from onset along the nerve.MethodsCompound impedance changes (dZ) were simulated using an electrically stimulated CAPs in 1D FEM model of a C fibre [1], with statistical analysis for 5000 fibres with conduction velocities 0.6±0.07 m/s (mean±SD) [2]. This enabled simulation of dZ up to 20 cm from the stimulus with stimulus trains of 5/10/20/50 Hz lasting 0.25–8 s with 3 s intervals between trains (Fig. 1a). The total duration of each simulation was 100 s.dZ was simulated 1) By coherent averaging of responses of supramaximal activity of single spikes [3] with demodulation bandwidth of 50–300 Hz and 2) By bandpass filtering of entire evoked spike trains with bandwidths of 0.25–5 Hz which allowed significant reduction of the noise without the need for coherent spike averaging.Random gaussian noise (0.015 μV RMS) was added to the signal to simulate realistic recording conditions. The SNR in the utilised approaches was computed for all tested stimulation and recording paradigms and compared.ResultsWhile coherent spike averaging was superior at short distances, its SNR fell exponentially with the distance from the onset (Fig. 1b, solid lines). The SNR with the compound demodulation was more consistent across distances (~2 at the optimal stimulation frequency of 20 Hz, Fig. 1b, dashed lines) allowing recording at ≥ 20 cm from stimulation. The estimated minimal averaging time required to obtain an SNR of 4 at 20 cm from the stimulus was equal to approximately 30 minutes at 20 Hz.Conclusion and future workThe developed stimulation and signal processing paradigm demonstrated the feasibility of dZ recording at long distances from the stimulus. Future work is to validate it on the ex vivo crustacean leg nerve model and subsequently an in vivo mammalian model with the final objective of imaging C fibres in the vagus nerve in humans. If successful, this technique will be applied for improvement of the emerging field of bioelectronic medicines [4].Support or Funding InformationThe work was supported by NIH SPARC grant no: 3OT2OD026545‐01S2.(a) Example of AP and dZ responses of the C fibre subjected to repetitive 50 Hz stimuli; (b) SNR computed for the single and compound recording paradigms.Figure 1

Optimization of the electrode drive pattern for imaging fascicular compound action potentials in peripheral nerve with fast neural electrical impedance tomography

Objective: The main objective of this study was to investigate which injection pattern led to the best imaging of fascicular compound activity in fast neural EIT of peripheral nerve using an external cylindrical 2  ×  14-electrodes cuff. Specifically, the study addressed the identification of the optimal injection pattern and of the optimal region of the reconstructed volume to image fascicles. Approach: The effect of three different measurement protocol features (transversal/longitudinal injection, drive electrode spacing, referencing configuration) over imaging was investigated in simulation with the use of realistic impedance changes and noise levels. Image-based metrics were employed to evaluate the quality of the reconstructions over the reconstruction domain. The optimal electrode addressing protocol suggested by the simulations was validated in vivo on the tibial and peroneal fascicles of rat sciatic peripheral nerves (N  =  3) against MicroCT reference images. Main results: Injecting current transversally, with spacing of  ⩾4 electrodes apart (⩾100°) and single-ring referencing of measurements, led to the best overall localization when reconstructing on the edge of the electrode array closest to the reference. Longitudinal injection protocols led to a higher SNR of the reconstructed image but poorer localization. All in vivo EIT recordings had statistically significant impedance variations (p   <  0.05). Overall, fascicle center-of-mass (CoM) localization error was estimated at 141  ±  56 µm (−26  ±  94 µm and 5  ±  29° in radial coordinates). Significant difference was found (p   <  0.05) between mean angular location of the tibial and peroneal CoMs. Significance: This study gives the reader recommendations for performing fast neural EIT of fascicular compound activity using the most effective protocol features.

Simulation of impedance changes with a FEM model of a myelinated nerve fibre

Objective. Fast neural electrical impedance tomography (EIT) is a method which permits imaging of neuronal activity in nerves by measuring the associated impedance changes (dZ). Due to the small magnitudes of dZ signals, EIT parameters require optimization, which can be done using in silico modelling: apart from predicting the best parameters for imaging, it can also help to validate experimental data and explain the nature of the observed dZ. This has previously been completed for unmyelinated fibres, but an extension to myelinated fibres is required for the development of a full nerve model which could aid imaging neuronal traffic at the fascicular level and optimise neuromodulation of the supplied internal organs to treat various diseases. Approach. An active finite element method (FEM) model of a myelinated fibre coupled with external space was developed. A spatial dimension was added to the experimentally validated space-clamped model of a human sensory fibre using the double cable paradigm. Electrical parameters of the model were changed so that nodal and internodal membrane potential as well as propagation velocity agreed with experimental values. Impedance changes were simulated during activity under various conditions and the optimal parameters for imaging were determined. Main results. When using AC, dZ could be recorded only at frequencies above 4 kHz, which is supported by experimental data. Optimal bandwidths for dZ measurement were found to increase with AC frequency. Significance. The novel fully bi-directionally coupled FEM model of a myelinated fibre was able to optimize EIT for myelinated fibres and explain the biophysical basis of the measured signals.

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.

Electrode fabrication and interface optimization for imaging of evoked peripheral nervous system activity with electrical impedance tomography (EIT)

Objective. Non-invasive imaging techniques are undoubtedly the ideal methods for continuous monitoring of neural activity. One such method, fast neural electrical impedance tomography (EIT) has been developed over the past decade in order to image neural action potentials with non-penetrating electrode arrays. Approach. The goal of this study is two-fold. First, we present a detailed fabrication method for silicone-based multiple electrode arrays which can be used for epicortical or neural cuff applications. Secondly, we optimize electrode material coatings in order to achieve the best accuracy in EIT reconstructions. Main results. The testing of nanostructured electrode interface materials consisting of platinum, iridium oxide, and PEDOT:pTS in saline tank experiments demonstrated that the PEDOT:pTS coating used in this study leads to more accurate reconstruction dimensions along with reduced phase separation between recording channels. The PEDOT:pTS electrodes were then used in vivo to successfully image and localize the evoked activity of the recurrent laryngeal fascicle from within the cervical vagus nerve. Significance. These results alongside the simple fabrication method presented here position EIT as an effective method to image neural activity.

Imaging fast neural traffic at fascicular level with electrical impedance tomography: proof of principle in rat sciatic nerve

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 non-penetrating peri-neural device.

F36. Imaging fascicle traffic in peripheral nerve using fast neural EIT

Fast neural Electrical Impedance Tomography (EIT) is a promising technique which can potentially be used for imaging neural activity over milliseconds with unprecedented spatial resolution without penetrating nervous tissue. Here we present the first cross-sectional images of fascicular neural activity measured during compound action potentials acquired in rat sciatic nerve in in vivo experiments. EIT was collected with a cylindrical cuff electrode wrapped around the sciatic nerve in the thigh in 4 adult Sprague-Dawley rats anaesthetized with Isoflurane nerve made of silicone rubber. 16 electrodes were placed around the circumference, each 2 × 0.1 mm, made of laser-cut stainless steel foil which was then platinised. Distal fibular and tibial branches were electrically stimulated with square pulses with 0.2 ms duration, 1 mA amplitude, and 200 ms inter–stimulus interval. EIT data was acquired during consecutive injection of alternating current, with amplitude 5–75 μA and frequency 3–15 kHz, through a pair of electrodes at a time with simultaneous voltage recordings on the remaining electrodes. 16 independent current injections with 50 pulses per injection were recorded, resulting in 160 s image acquisition time. Acquired data was demodulated with 4 kHz bandwidth, averaged, and reconstructed with >0.5 ms temporal resolution. 1M-element 3D forward mesh, and 20k-element inverse mesh was used for reconstruction; 0-th order Tikhonov regularisation with coefficient of variance correction was employed. Results were displayed as a Z-score with respect to the inter-stimulus noise. Reproducible time-series images were reconstructed in each experiment, showing neural activity onset in ∼0.3–0.6 ms, after stimulus, peak at 0.6–1.5 ms, and subsequent decay at 1–2 ms. Images were obtained following electrical stimulation of the tibial or peroneal branches distally. Spatially distinguishable activity with centre-to-centre separation distance of 0.57 ± 0.04 mm (mean ± S.E.) was obtained in N = 24 experiments in n = 3 rats. EIT were much superior to those collected by Inverse Source Analysis (ISA) performed on CAPs recorded simultaneously to the EIT. Images were cross-validated with co-registered histological images. Comparison showed the position mismatch was 0.1 mm ± 0.03 mm between EIT and histology, and 0.14 mm ± 0.06 mm between EIT and inverse source imaging. Nerve fascicular traffic can be successfully imaged using EIT. This offers a potential means to identify the function of fascicles in autonomic nerve in vivo and so avoid off-target effect by selective stimulation. This could yield significant benefits in vagal nerve stimulation in epilepsy, where hoarseness is a limiting factor, and in the new field of Electroceutical treatment of disease by electrical stimulation of autonomic nerve.

T16. Imaging propagation of ictal spike-and-wave activity in the cerebral cortex over milliseconds with fast neural electrical impedance tomography

Introduction Electrical Impedance Tomography (EIT) is an emerging medical imaging modality in which the internal impedance of a subject can be imaged using boundary voltage measurements from non-penetrating surface electrodes. It can be used to image neuronal depolarisation over milliseconds as impedance falls when ion channels open during neuronal depolarization. EIT of fast electrical activity due to neuronal depolarisation in the rat cerebral cortex has previously been undertaken with a resolution of 2 ms and μ m using epicortical electrode arrays during evoked potentials and interictal spikes. The purpose of the current work was to use EIT to image ictal spike-wave discharges (SWDs) in the rat cortex and examine the possibility of determining the propagation pattern of this activity through cortical layers. Methods Adult female Sprague-Dawley rats (300–450 g) were anaesthetised with isoflurane; anaesthesia was maintained after surgery with isoflurane and intravenous fentanyl. A large craniotomy was performed on one hemisphere before implanting a 15 × 9 mm257-electrode array, fabricated from stainless steel and silicone rubber, on the cortical surface. Epileptiform events were induced by electrically stimulating the sensorimotor cortex with a 5-s train of 1–2 mA biphasic, charge-balanced square-wave pulses at 100 Hz. For EIT recordings, a 50  μ A sine-wave was injected at 1.7 kHz through a different electrode pair for each of ∼ 30 seizures. EIT images were produced with trigger markers at the peak amplitude of SWDs in the ECoG, averaging over time within one seizure, and over different current pair applications for successive seizures, demodulation of the EIT signal with a ± 500 Hz bandwidth and reconstruction of the processed voltages to produce images with a resolution of 300  μ m and Results There was a maximum impedance change of −0.31 ± 0.06% during the spike phase of averaged SWDs, the early focus of which was spatially confined to the infragranular layers of the primary somatosensory cortex (p  Conclusion Fast neural EIT is a novel method which permits visualisation of the trajectory of propagation of ictal activity over milliseconds through the cerebral cortex. This has potential for improving understanding of the pathophysiology of such paroxysmal events and tracking the trajectory of ictal activity throughout the brain in 3D. This could provide a complementary clinical tool to help localise the epileptogenic zone in treatment-resistant focal epilepsies during presurgical evaluation.

T15. Imaging fast neuronal depolarization in 3D during seizures with electrical impedance tomography and scalp and intracranial depth electrodes

Electrical Impedance Tomography (EIT) is an imaging technique where internal conductivity changes in an object are reconstructed from measurements with arrays of external electrodes. It has the potential to improve epileptogenic zone localisation as seizure activity changes local impedance in two ways. ‘Fast’ changes, ∼1% over millseconds, are due to the opening of ion channels during synchronised neuronal depolarisation, and ‘slow’ changes, up to 10% over seconds, are due to cell swelling. During SEPs in anaethetised rats, EIT could image evoked activity in S1 with a resolution of 1 ms and <200 μm using 30 electrode epicortical arrays. EIT could offer improved resolution over the current technique of inspection of potentials with depth electrodes (SEEG) in patients undergoing presurgical seizure evaluation. EIT has the advantage that it is not sensitive to dipole orientation and coverage within a volume enclosed by electrodes is much better than for potential recording. The purpose of this study was to undertake a computer modelling study to compare fast neural EIT with SEEG and EEG inverse source modelling in subjects with epilepsy and intracranial electrodes. The location and shape accuracy of reconstructed changes were assessed in 3 subjects with 48–72 depth electrode contacts and 32 scalp electrodes with EIT (1.7 kHz, 50 μA intracranial, 250 μA scalp), EEG inverse source modelling (ISM), and spike detection on depth electrodes (SEEG), using FEM meshes of ∼9 M tetrahedral elements generated from CT-MRI. EIT and inverse source reconstructions were performed on ∼30,000 hexahedral element meshes with zeroth order Tikhonov regularisation and noise-based image weighting. Seizure onset was simulated by 5 mm radius realistic perturbations of 1% and 10% or dipoles which produced 2 mV when 5 mm away from an electrode (5 within and 5 outside the volume enclosed by depth electrodes in each subject). EIT produced the best localisation. It was far superior to ISM and also provided accurate imaging for dipole sources not apparent on SEEG because of distance from the nearest electrode or tangential orientation. For perturbations placed within the depth electrodes, localisation accuracy was 5.2 ± 1.8 mm (1% change) <5 mm (10% change) for EIT and 46.2 ± 25.8 mm for ISM with radially oriented sources. For SEEG, 7/15 radially oriented sources did not reach a visualisable threshold set as 250 μV which occurred when they were >11 mm distant from the nearest electrode. For the sources in the opposite hemisphere, it was 29.6 ± 38.7 mm (1% EIT), 26.1 ± 36.2 (10% EIT), 54.0 ± 26.2 mm (ISM) and 0/15(SEEG). In this modelling study, fast and slow neural EIT with depth electrode offers a new method for localisation of seizure onset and propagation. It employs tiny injected currents which do not damage the brain or alter cerebral function. It offers a potentially valuable additional method for presurgical epilepsy evaluation. A human clinical trial is in progress.

Characterising the frequency response of impedance changes during evoked physiological activity in the rat brain

Objective: Electrical impedance tomography (EIT) can image impedance changes associated with evoked physiological activity in the cerebral cortex using an array of epicortical electrodes. An impedance change is observed as the externally applied current, normally confined to the extracellular space is admitted into the conducting intracellular space during neuronal depolarisation. The response is largest at DC and decreases at higher frequencies due to capacitative transfer of current across the membrane. Biophysical modelling has shown that this effect becomes significant above 100 Hz. Recordings at DC, however, are contaminated by physiological endogenous evoked potentials. By moving to 1.7 kHz, images of somatosensory evoked responses have been produced down to 2 mm with a resolution of 2 ms and 200 μm. Hardware limitations have so far restricted impedance measurements to frequencies  <2 kHz. The purpose of this work was to establish the optimal frequency for extending EIT to image throughout the brain and to characterise the response at frequencies  >2 kHz using improved hardware. Approach: Impedance changes were recorded during forepaw somatosensory stimulation in both cerebral cortex and the VPL nucleus of the thalamus in anaesthetised rats using applied currents of 1 kHz to 10 kHz. Main results: In the cortex, impedance changed by –0.04 ± 0.02 % at 1 kHz, reached a peak of –0.13 ± 0.05 % at 1475 Hz and decreased to –0.05 ± 0.02 % at 10 kHz. At these frequencies, changes in the thalamus were –0.26 ± 0.1%, –0.4 ± 0.15 % and –0.08 ± 0.03 % respectively. The signal-to-noise ratio was also highest at 1475 Hz with values of –29.5 ± 8 and –31.6 ±10 recorded from the cortex and thalamus respectively. Signficance: This indicates that the optimal frequency for imaging cortical and thalamic evoked activity using fast neural EIT is 1475 Hz.

Investigation of potential artefactual changes in measurements of impedance changes during evoked activity: implications to electrical impedance tomography of brain function

Electrical impedance tomography (EIT) could provide images of fast neural activity in the adult human brain with a resolution of 1 ms and 1 mm by imaging impedance changes which occur as ion channels open during neuronal depolarization. The largest changes occur at dc and decrease rapidly over 100 Hz. Evoked potentials occur in this bandwidth and may cause artefactual apparent impedance changes if altered by the impedance measuring current. These were characterized during the compound action potential in the walking leg nerves of Cancer pagurus, placed on Ag/AgCl hook electrodes, to identify how to avoid artefactual changes during brain EIT. Artefact-free impedance changes (δZ) decreased with frequency from −0.045 ± 0.01% at 225 Hz to −0.02 ± 0.01% at 1025 Hz (mean ± 1 SD, n = 24 in 12 nerves) which matched changes predicted by a finite element model. Artefactual δZ reached c.300% and 50% of the genuine membrane impedance change at 225 Hz and 600 Hz respectively but decreased with frequency of the applied current and was negligible above 1 kHz. The proportional amplitude (δZ (%)) of the artefact did not vary significantly with the amplitude of injected current of 5–20 µA pp. but decreased significantly from −0.09 ± 0.024 to −0.03 ± 0.023% with phase of 0 to 45°. For fast neural EIT of evoked activity in the brain, artefacts may arise with applied current of >10 µA. Independence of δZ with respect to phase but not the amplitude of applied current controls for them; they can be minimized by randomizing the phase of the applied measuring current and excluded by recording at >1 kHz.

A method for reconstructing tomographic images of evoked neural activity with electrical impedance tomography using intracranial planar arrays

A method is presented for reconstructing images of fast neural evoked activity in rat cerebral cortex recorded with electrical impedance tomography (EIT) and a 6 × 5 mm2 epicortical planar 30 electrode array. A finite element model of the rat brain and inverse solution with Tikhonov regularization were optimized in order to improve spatial resolution and accuracy. The optimized FEM mesh had 7 M tetrahedral elements, with finer resolution (0.05 mm) near the electrodes. A novel noise-based image processing technique based on t-test significance improved depth localization accuracy from 0.5 to 0.1 mm. With the improvements, a simulated perturbation 0.5 mm in diameter could be localized in a region 4 × 5 mm2 under the centre of the array to a depth of 1.4 mm, thus covering all six layers of the cerebral cortex with an accuracy of <0.1 mm. Simulated deep brain hippocampal or thalamic activity could be localized with an accuracy of 0.5 mm with a 256 electrode array covering the brain. Parallel studies have achieved a temporal resolution of 2 ms for imaging fast neural activity by EIT during evoked activity; this encourages the view that fast neural EIT can now resolve the propagation of depolarization-related fast impedance changes in cerebral cortex and deeper in the brain with a resolution equal or greater to the dimension of a cortical column.