A modelling study to inform specification and optimal electrode placement for imaging of neuronal depolarization during visual evoked responses by electrical and magnetic detection impedance tomography.

Electrical impedance tomography (EIT) has the potential to achieve non-invasive functional imaging of fast neuronal activity in the human brain due to opening of ion channels during neuronal depolarization. Local changes of resistance in the cerebral cortex are about 1%, but the size and location of changes recorded on the scalp are unknown. The purpose of this work was to develop an anatomically realistic finite element model of the adult human head and use it to predict the amplitude and topography of changes on the scalp, and so inform specification for an in vivo measuring system. A detailed anatomically realistic finite element (FE) model of the head was produced from high resolution MRI. Simulations were performed for impedance changes in the visual cortex during evoked activity with recording of scalp potentials by electrodes or magnetic flux density by magnetoencephalography (MEG) in response to current injected with electrodes. The predicted changes were validated by recordings in saline filled tanks and with boundary voltages measured on the human scalp. Peak changes were 1.03 +/- 0.75 microV (0.0039 +/- 0.0034%) and 27 +/- 13 fT (0.2 +/- 0.5%) respectively, which yielded an estimated peak signal-to-noise ratio of about 4 for in vivo averaging over 10 min and 1 mA current injection. The largest scalp changes were over the occipital cortex. This modelling suggests, for the first time, that reproducible changes could be recorded on the scalp in vivo in single channels, although a higher SNR would be desirable for accurate image production. The findings suggest that an in vivo study is warranted in order to determine signal size but methods to improve SNR, such as prolonged averaging or other signal processing may be needed for accurate image production.

Design of electrodes and current limits for low frequency electrical impedance tomography of the brain.

For the novel application of recording of resistivity changes related to neuronal depolarization in the brain with electrical impedance tomography, optimal recording is with applied currents below 100 Hz, which might cause neural stimulation of skin or underlying brain. The purpose of this work was to develop a method for application of low frequency currents to the scalp, which delivered the maximum current without significant stimulation of skin or underlying brain. We propose a recessed electrode design which enabled current injection with an acceptable skin sensation to be increased from 100 muA using EEG electrodes, to 1 mA in 16 normal volunteers. The effect of current delivered to the brain was assessed with an anatomically realistic finite element model of the adult head. The modelled peak cerebral current density was 0.3 A/m(2), which was 5 to 25-fold less than the threshold for stimulation of the brain estimated from literature review.

Multi-frequency electrical impedance tomography (EIT) of the adult human head: initial findings in brain tumours, arteriovenous malformations and chronic stroke, development of an analysis method and calibration.

MFEIT (multi-frequency electrical impedance tomography) could distinguish between ischaemic and haemorrhagic stroke and permit the urgent use of thrombolytic drugs in patients with ischaemic stroke. The purpose of this study was to characterize the UCLH Mk 2 MFEIT system, designed for this purpose, with 32 electrodes and a multiplexed 2 kHz to 1.6 MHz single impedance measuring circuit. Data were collected in seven subjects with brain tumours, arteriovenous malformations or chronic stroke, as these resembled the changes in haemorrhagic or ischaemic stroke. Calibration studies indicated that the reliable bandwidth was only 16-64 kHz because of front-end components placed to permit simultaneous EEG recording. In raw in-phase component data, the SD of 16-64 kHz data for one electrode combination across subjects was 2.45 +/- 0.9%, compared to a largest predicted change of 0.35% estimated using the FEM of the head. Using newly developed methods of examining the most sensitive channels from the FEM, and nonlinear imaging constrained to the known site of the lesion, no reproducible changes between pathologies were observed. This study has identified a specification for accuracy in EITS in acute stroke, identified the size of variability in relation to this in human recordings, and presents new methods for analysis of data. Although no reproducible changes were identified, we hope this will provide a foundation for future studies in this demanding but potentially powerful novel application.

Factors limiting the application of electrical impedance tomography for identification of regional conductivity changes using scalp electrodes during epileptic seizures in humans.

Electrical impedance tomography (EIT) has the potential to produce images during epileptic seizures. This might improve the accuracy of the localization of epileptic foci in patients undergoing presurgical assessment for curative neurosurgery. It has already been shown that impedance increases by up to 22% during induced epileptic seizures in animal models, using cortical or implanted electrodes in controlled experiments. The purpose of this study was to determine if reproducible raw impedance changes and EIT images could be collected during epileptic seizures in patients who were undergoing observation with video-electroencephalography (EEG) telemetry as part of evaluation prior to neurosurgery to resect the region of brain causing the epilepsy. A secondary purpose was to develop an objective method for processing and evaluating data, as seizures arose at unpredictable times from a noisy baseline. Four-terminal impedance measurements from 258 combinations were collected continuously using 32 EEG scalp electrodes in 22 seizure episodes from 7 patients during their presurgical assessment together with the standard EEG recordings. A reliable method for defining the pre-seizure baseline and recording impedance data and EIT images was developed, in which EIT and EEG could be acquired simultaneously after filtering of EIT artefact from the EEG signal. Fluctuations of several per cent over minutes were observed in the baseline between seizures. During seizures, boundary voltage changes diverged with a standard deviation of 1-54% from the baseline. No reproducible changes with the expected time course of some tens of seconds and magnitude of about 0.1% could be reliably measured. This demonstrates that it is feasible to acquire EIT images in parallel with standard EEG during presurgical assessment but, unfortunately, expected EIT changes on the scalp of about 0.1% are swamped by much larger movement and systematic artefact. Nevertheless, EIT has the unique potential to provide invaluable neuroimaging data for this purpose and may still become possible with improvements in electrode design and instrumentation.

Design and calibration of a compact multi-frequency EIT system for acute stroke imaging.

A new, compact UCLH Mk 2.5 EIT system has been developed and calibrated for EIT imaging of the head. Improvements include increased input and output impedances, increased bandwidth and improved CMRR (80 dB) and linearity over frequencies and load (0.2% on a single channel, +/-0.7% on a saline tank over 20 Hz-256 kHz and 10-65 Omega). The accuracy of the system is sufficient to image severe acute stroke according to the specification from recent detailed anatomical modelling (Horesh et al 2005 3rd European Medical and Biological Engineering Conference EMBEC'05). A preliminary human study has validated the main specifications of the modelling, the range of trans-impedance from the head (8-70 Omega) using a 32 electrode, 258 combination protocol and contact impedances of 300 Omega to 2.7 kOmega over 20 Hz to 256 kHz.

Applications of GRID in clinical neurophysiology and Electrical Impedance Tomography of brain function.

The computational requirements in Neurophysiology are increasing with the development of new analysis methods. The resources the GRID has to offer are ideally suited for this complex processing. A practical implementation of the GRID, Condor, has been assessed using a local cluster of 920 PCs. The reduction in processing time was assessed in spike recognition of the Electroencephalogram (EEG) in epilepsy using wavelets and the computationally demanding task of non-linear image reconstruction with Electrical Impedance Tomography (EIT). Processing times were decreased by 25 and 40 times respectively. This represents a substantial improvement in processing time, but is still sub optimal due to factors such as shared access to resources and lack of checkpoints so that interrupted jobs had to be restarted. Future work will be to use these methods in non-linear EIT image reconstruction of brain function and methods for automated EEG analysis, if possible with further optimized GRID middleware.

Using the GRID to improve the computation speed of electrical impedance tomography (EIT) reconstruction algorithms.

In our group at University College London, we have been developing electrical impedance tomography (EIT) of brain function. We have attempted to improve image quality by the use of realistic anatomical meshes and, more recently, non-linear reconstruction methods. Reconstruction with linear methods, with pre-processing, may take up to a few minutes per image for even detailed meshes. However, iterative non-linear reconstruction methods require much more computational resources, and reconstruction with detailed meshes was taking far too long for clinical use. We present a solution to this timing bottleneck, using the resources of the GRID, the development of coordinated computing resources over the internet that are not subject to centralized control using standard, open, general-purpose protocols and are transparent to the user. Optimization was performed by splitting reconstruction of image series into individual jobs of one image each; no parallelization was attempted. Using the GRID middleware 'Condor' and a cluster of 920 nodes, reconstruction of EIT images of the human head with a non-linear algorithm was speeded up by 25-40 times compared to serial processing of each image. This distributed method is of direct practical value in applications such as EIT of epileptic seizures where hundreds of images are collected over the few minutes of a seizure and will be of value to clinical data collection with similar requirements. In the future, the same resources could be employed for the more ambitious task of parallelized code.

Generating accurate finite element meshes for the forward model of the human head in EIT.

The use of realistic anatomy in the model used for image reconstruction in EIT of brain function appears to confer significant improvements compared to geometric shapes such as a sphere. Accurate model geometry may be achieved by numerical models based on magnetic resonance images (MRIs) of the head, and this group has elected to use finite element meshing (FEM) as it enables detailed internal anatomy to be modelled and has the capability to incorporate information about tissue anisotropy. In this paper a method for generating accurate FEMs of the human head is presented where MRI images are manually segmented using custom adaptation of industry standard commercial design software packages. This is illustrated with example surface models and meshes from adult epilepsy patients, a neonatal baby and a phantom latex tank incorporating a real skull. Mesh quality is assessed in terms of element stretch and hence distortion.

Digital subtraction versus film-screen angiography for detecting acute pulmonary emboli: evaluation in a porcine model.

PURPOSE: To compare the diagnostic performance of digital subtraction angiography (DSA) to that of film-screen angiography (FSA) for detecting acute pulmonary embolism (PE) in a porcine model. MATERIALS AND METHODS: DSA and FSA were performed in 13 pigs before and after central venous administration of autologous emboli. Results were compared to findings at necropsy with use of ex vivo pulmonary angiography to guide pathologic sectioning. The sensitivity and predictive value of a positive case for detecting each embolus were computed for each pulmonary artery branch order and compared with use of 95% confidence intervals. Interobserver variability among three readers for individual PE detection was calculated. RESULTS: Pathologic examination of the lungs revealed 100 total PEs (location by vessel order: 1st = 1, 2nd = 0, 3rd = 15, 4th = 32, > 5th = 52). On average, FSA review identified 72 (72%) emboli and DSA review, 65 (65%). There was no significant difference in sensitivity or predictive value of a positive case between DSA and FSA for detecting emboli (P > .05). There was similar agreement among readers for individual PE detection with DSA (mean, 84%) and FSA (mean, 80%). CONCLUSION: The diagnostic performance of DSA is equivalent to that of FSA for detecting emboli in porcine PA branches. Interobserver agreement for individual PE detection is similar for both imaging techniques.

Depiction of pulmonary emboli with spiral CT: optimization of display window settings in a porcine model.

PURPOSE: To determine optimal spiral computed tomographic (CT) image display for depiction of pulmonary emboli (PE). MATERIALS AND METHODS: Autologous PE detected in 10 pigs with contrast material-enhanced spiral CT were displayed with six display window settings (standard mediastinal window and five modified windows referenced to attenuation values in pulmonary artery [PA] branches). The thrombus gray level and gray level contrast and separability of PE versus those of the local PA branch were computed for each window setting; results were compared with repeated measured analysis of variance. RESULTS: Of 114 PE detected pathologically, 28 were visible with spiral CT. Two of the 28 PE were not detectable with standard mediastinal windows. Statistically significantly improved gray level contrast and separability were noted with modified windows referenced to the second-order PA branch and the local PA branch than with the standard mediastinal and other modified window settings (P < .05). However, thrombus gray level was statistically significantly higher with the standard mediastinal window (P < .05). CONCLUSION: PE are best depicted as filling defects when displayed with a modified window referenced to the right or left main PA attenuation. Standard mediastinal windows are useful for identifying vessels that are occluded completely with PE.