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

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

High-throughput mechanobiology: Force modulation of ensemble biochemical and cell-based assays

Mechanobiology is focused on how the physical forces and mechanical properties of proteins, cells, and tissues contribute to physiology and disease. Although the response of proteins and cells to mechanical stimuli is critical for function, the tools to probe these activities are typically restricted to single-molecule manipulations. Here, we have developed a novel microplate reader assay to encompass mechanical measurements with ensemble biochemical and cellular assays, using a microplate lid modified with magnets. This configuration enables multiple static magnetic tweezers to function simultaneously across the microplate, thereby greatly increasing throughput. We demonstrate the broad applicability and versatility through in vitro and in cellulo approaches. Overall, our methodology allows, for the first time (to our knowledge), ensemble biochemical and cell-based assays to be performed under force in high-throughput format. This approach substantially increases the availability of mechanobiology measurements

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

Using patient-reported outcome measures to evaluate care for patients with inflammatory chronic rheumatic disease

Objectives: Few countries integrate Patient-Reported Outcome Measures (PROMs) in routine performance assessment, and those that do focus on elective surgery. This study addresses the challenges of using PROMs to evaluate care in chronic conditions. We set out a modelling strategy to assess the extent to which changes over time in self-reported health status by patients with inflammatory chronic rheumatic disease are related to their biological drug therapy and Rheumatology centre primarily responsible for their care. Methods: Using data from the Portuguese Register of Rheumatic Diseases, we assess the health status using the Health Assessment Questionnaire-Disability Index (HAQ-DI) for rheumatic patients receiving biological drugs between 2000 and 2017. We employ a fixed effects model using the Least Squares Dummy Variables estimator. Results: Patients receiving infliximab or rituximab report lower health status than those on etanercept (the most common therapy) and patients in 4 of the 26 Rheumatology centres report higher health status than those at other centres. Conclusions: PROMs can be used for those with chronic conditions to provide the patient’s perspective about the impact on their health status of the choice of drug therapy and care provider. Care for chronic patients might be improved if healthcare organisations monitor PROMs and engage in performance assessment initiatives on a routine basis

On the complexity of color-avoiding site and bond percolation

The mathematical analysis of robustness and error-tolerance of complex networks has been in the center of research interest. On the other hand, little work has been done when the attack-tolerance of the vertices or edges are not independent but certain classes of vertices or edges share a mutual vulnerability. In this study, we consider a graph and we assign colors to the vertices or edges, where the color-classes correspond to the shared vulnerabilities. An important problem is to find robustly connected vertex sets: nodes that remain connected to each other by paths providing any type of error (i.e. erasing any vertices or edges of the given color). This is also known as color-avoiding percolation. In this paper, we study various possible modeling approaches of shared vulnerabilities, we analyze the computational complexity of finding the robustly (color-avoiding) connected components. We find that the presented approaches differ significantly regarding their complexity.Comment: 14 page

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 mm(2) 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 mm(2) 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