Development of Methodologies for the Solution of the Forward Problem in Magnetic-Field Tomography (MFT) Based on Magnetoencephalography (MEG)

The prime topic of research presented in this report is the development and validation of methodologies for the solution of the forward problem in Magnetic field Tomography based on Magnetoencephalography. Throughout the report full aspects of the accurate solution are discussed, including the development of algorithms and methods for realistic brain model, development of realistic neuronal source, computational approaches, and validation techniques. Every delivered methodology is tested and analyzed in terms of mathematical and computational errors. Optimizations required for error minimization are performed and discussed. Presented techniques are successfully integrated together for different test problems. Results were compared to experimental data where possible for the most of calculated cases. Designed human brain model reconstruction algorithms and techniques, which are based on MRI (Magnetic Resonance Imaging) modality, are proved to be the most accurate among existing in terms of geometrical and material properties. Error estimations and algorithm structure delivers the resolution of the model to be the same as practical imaging resolution of the MRI equipment (for presented case was less than 1mm). Novel neuronal source modelling approach was also presented with partial experimental validation showing improved results in comparison to all existing methods. At the same time developed mathematical basis for practical realization of discussed approach allows computer simulations of any known neuronal formation. Also it is the most suitable method for Finite Element Method (FEM) which was proved to be the best computer solver for complex bio-electrical problems. The mathematical structure for Inverse problem solution which is based on integrated human brain modelling technique and neuronal source modelling approach is delivered and briefly discussed. In the concluding part of the report the practical application case of developed techniques is performed and discussed

Development of methodologies for the solution of the forward problem in magnetic-field tomography (MFT) based on magnetoencephalography (MEG)

The prime topic of research presented in this report is the development and validation of methodologies for the solution of the forward problem in Magnetic field Tomography based on Magnetoencephalography. Throughout the report full aspects of the accurate solution are discussed, including the development of algorithms and methods for realistic brain model, development of realistic neuronal source, computational approaches, and validation techniques. Every delivered methodology is tested and analyzed in terms of mathematical and computational errors. Optimizations required for error minimization are performed and discussed. Presented techniques are successfully integrated together for different test problems. Results were compared to experimental data where possible for the most of calculated cases. Designed human brain model reconstruction algorithms and techniques, which are based on MRI (Magnetic Resonance Imaging) modality, are proved to be the most accurate among existing in terms of geometrical and material properties. Error estimations and algorithm structure delivers the resolution of the model to be the same as practical imaging resolution of the MRI equipment (for presented case was less than 1mm). Novel neuronal source modelling approach was also presented with partial experimental validation showing improved results in comparison to all existing methods. At the same time developed mathematical basis for practical realization of discussed approach allows computer simulations of any known neuronal formation. Also it is the most suitable method for Finite Element Method (FEM) which was proved to be the best computer solver for complex bio-electrical problems. The mathematical structure for Inverse problem solution which is based on integrated human brain modelling technique and neuronal source modelling approach is delivered and briefly discussed. In the concluding part of the report the practical application case of developed techniques is performed and discussed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

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

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 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

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 &lt;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

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

OBJECTIVE: Fast neural Electrical Impedance Tomography (FnEIT) 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 EIT 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 FEM-based statistical model of temporal dispersion 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 (SNR) 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 minutes. 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

High-resolution imaging of fast neural activity in the brain with Electrical Impedance Tomography

We present the first EIT images of evoked physiological activity in the primary somatosensory cortex (S1) obtained with intracranial planar electrode array. Images were validated using intrinsic signal optical imaging (ISOI) and current source-sink density analysis (CSDA). Detailed high-resolution spatiotemporal connectivity of the brain cortex was reconstructed with ≤200μm and ≤2ms

120-channel electrode arrays for rat brain: Towards 3D EIT imaging

EIT has much potential in many brain imaging applications demonstrated through animal experiments with a small epicortical 30-channel array. Spatial resolution can be improved by using a larger array to cover most of brain. A 120-channel electrode system was fabricated and successfully implanted covering c.90% of brain, and EIT data was successfully recorded

Organotopic organization of the porcine mid-cervical vagus nerve

Introduction: 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. / Methods and results: 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. / Discussion: 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