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

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 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±287µV and 487±279µV, p=0.28) and impedance changes (36±14µV and 31±16µV, 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. 40µm) difference in peak location and a high degree of correlation (R2=0.97). When down-sampling from 24 to 16 bits ADC resolution and from 100KHz to 50KHz 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 R2=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

A comparison of techniques to optimize measurement of voltage changes in electrical impedance tomography by minimizing phase shift errors

In electrical impedance tomography, errors due to stray capacitance may be reduced by optimization of the reference phase of the demodulator. Two possible methods, maximization of the demodulator output and minimization of reciprocity error have been assessed, applied to each electrode combination individually, or to all combinations as a whole. Using an EIT system with a single impedance measuring circuit and multiplexer to address the 16 electrodes, the methods were tested on resistor-capacitor networks, saline-filled tanks and humans during variation of the saline concentration of a constant fluid volume in the stomach. Optimization of each channel individually gave less error, particularly on humans, and maximization of the output of the demodulator was more robust. This method is, therefore, recommended to optimize systems and reduce systematic errors with similar EIT systems

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

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 2x14-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±56µm (-26±94µm 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

Imaging fast electrical activity in the brain with electrical impedance tomography.

Imaging of neuronal depolarization in the brain is a major goal in neuroscience, but no technique currently exists that could image neural activity over milliseconds throughout the whole brain. Electrical impedance tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of impedance changes with non-invasive surface electrodes. We report EIT imaging of impedance changes in rat somatosensory cerebral cortex with a resolution of 2ms and <200μm during evoked potentials using epicortical arrays with 30 electrodes. Images were validated with local field potential recordings and current source-sink density analysis. Our results demonstrate that EIT can image neural activity in a volume 7×5×2mm in somatosensory cerebral cortex with reduced invasiveness, greater resolution and imaging volume than other methods. Modeling indicates similar resolutions are feasible throughout the entire brain so this technique, uniquely, has the potential to image functional connectivity of cortical and subcortical structures

Effect of dispersion in nerve on compound action potential and impedance change: a modelling study

Objective: Electrical impedance tomography (EIT) is capable of imaging fast compound electrical activity (Compound Action Potentials, or CAPs) inside peripheral nerves. The ability of EIT to detect impedance changes (dZ) which arise from the opening of ion channels during the CAP is limited by the dispersion with distance from the site of onset, as fibres have differing conduction velocities. The effect is largest for autonomic nerves mainly formed of slower conducting unmyelinated fibres where signals cannot be recorded more than a few cm away from the stimulation. However, as CAPs are biphasic, monophasic dZ are expected to be detectable further than them; testing this hypothesis was the main objective of this study. Approach: An anatomically accurate FEM model and simplified statistical models of 50-fibre Hodgkin-Huxley and C-nociceptor nerves were developed with normally distributed conduction velocities; the statistical models were extended to realistic nerves. Results: 50- fibre models showed that dZ could persist further than biphasic CAPs, as these then cancelled. For realistic nerves consisting of Aα or Aβ fibres, significant dZ could be detected at 50-cm from the onset site with signal-to-noise ratios (SNR, mean ± s.d.) of 2.7±0.2 and 1.8±0.1 respectively; Aδ and rat sciatic nerve – at 20 cm (1.6±0.03 and 1.6±0.06), rat vagus – at 10 cm (1.6±0.05); C fibres – at 1-2 cm (2.4±0.02). Significance: This study provides a basis for determining the distance over which EIT may be used to image fascicular activity in electroceuticals and suggests dZ will persist further than CAPs if biphasic

Characterisation and imaging of cortical impedance changes during interictal and ictal activity in the anaesthetised rat.

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 12ms prior to the IISs, followed by a steep rise in impedance within ~120ms of the IIS. EIT images of these impedance changes showed that they were co-localised and centred at a depth of 1mm 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

Comparison of total variation algorithms for electrical impedance tomography

The applications of total variation (TV) algorithms for electrical impedance tomography (EIT) have been investigated. The use of the TV regularisation technique helps to preserve discontinuities in reconstruction, such as the boundaries of perturbations and sharp changes in conductivity, which are unintentionally smoothed by traditional l2 norm regularisation. However, the non-differentiability of TV regularisation has led to the use of different algorithms. Recent advances in TV algorithms such as the primal dual interior point method (PDIPM), the linearised alternating direction method of multipliers (LADMM) and the spilt Bregman (SB) method have all been demonstrated successful EIT applications, but no direct comparison of the techniques has been made. Their noise performance, spatial resolution and convergence rate applied to time difference EIT were studied in simulations on 2D cylindrical meshes with different noise levels, 2D cylindrical tank and 3D anatomically head-shaped phantoms containing vegetable material with complex conductivity. LADMM had the fastest calculation speed but worst resolution due to the exclusion of the second-derivative; PDIPM reconstructed the sharpest change in conductivity but with lower contrast than SB; SB had a faster convergence rate than PDIPM and the lowest image errors

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. Methods: An active 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. Conclusion and 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