Non-invasive Measurement of Cholesterol in Human Blood by Impedance Technique: an Investigation by Finite Element Field Modelling

The main topic of this work is detection of solid particles suspended in conductive medium and development of methodologies for determining cholesterol levels in human blood non-invasively by electrical impedance technique. The main part of this research is focused on the development of methodologies for numerical finite element (FE) modelling of simplified blood-cholesterol system, representing a real measurement system. This has been done first in 2D, to prove the concept and then in 3D, to take into account all of the effects that would only be present in 3D system as well as taking into account that there is a fully 3D problem in the heart of presented research. The proposed model has been tested in various extreme cases and theoretical and some experimental validations have been carried out to establish a degree of confidence in the modelling methodologies developed. This included novel way of model simplification by introduction of particle coagulation. This method has been proven to be successful replacement of effective conductivity method, used in the past. It has been tested against variation in physiological parameters, such as particle concentration and distribution, and material properties, such as particle ,conductivities. In 3D modelling cases the red blood cells (RBC) have been added to further increase the complexity of the system. Several case studies were used to help analyse which physical parameters of RBC would have the biggest impact on system’s impedance. Results were validated against experimental data where possible. This allowed extension of proposed methodology to non-spherical particles modelling. The other methodology adopted in this work applies to the electrode modelling. All electrodes are modelled as hollows. This tactic has been proven to work. It was validated both theoretically and by comparing computational model results with experiment results (BERG, City University London). In Conclusions, it is discussed that both methodologies can be used outside of current research in electromagnetic simulations of less conductive particles in conductive solvent and in cases where electrode material is not known. Modelling investigations of the simplified blood-cholesterol systems using the 2D and 3D FE modelling methodologies developed in this work have shown that it should be possible to measure cholesterol levels in human blood by impedance technique. Opinion sought from clinical staff highlight that this can potentially improve patient care by minimizing time needed for tests and human error (by shortening the number of people involved in testing). The work also establishes and discusses the need for further work, both theoretical and experimental for development of a measuring device for non-invasive measurement of cholesterol in human blood by impedance technique

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

Investigation of optimal parameters for finite element solution of the forward problem in magnetic field tomography based on magnetoencephalography

This paper presents an investigation of optimal parameters for finite element (FE) solution of the forward problem in magnetic field tomography (MFT) brain imaging based on magnetoencephalography (MEG). It highlights detailed analyses of the main parameters involved and evaluates their optimal values for various cases of FE model solutions (e.g., steady-state, transient, etc.). In each case, a detail study of some of the main parameters and their effects on FE solution and its accuracy are carefully tested and evaluated. These parameters include: total number and size of 3D FE elements used, number and size of elements used in surface discretisation (of both white and grey matters of the brain), number and size of elements used for approximation of current sources, number of anisotropic properties used in steady-state and transient solutions, and the time steps used in transient analyses. The optimal values of these parameters in relation to solution accuracy and mesh convergence criteria have been found and presented

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

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

BACKGROUND: The 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 METHOD: We 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. RESULTS: Recorded compound action potentials were larger with CF compared to SS (∼700μV vs ∼300μV); however, background noise was greater (6.3μV vs 1.7μV) leading to lower SNR. Maximum spatial discrimination between Centres-of-Mass of fascicular activity was achieved by fast neural EIT (402±30μm) and CF MEA (414±123μm), with no statistical difference between MicroCT (625±17μm) 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±51μm, p<0.05). COMPARISON WITH EXISTING METHODS: EIT 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. CONCLUSIONS: Nerve 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

Lumen shape reconstruction using a soft robotic balloon catheter and electrical impedance tomography

Incorrectly sized balloon catheters can lead to increased post-surgical complications, yet even with preoperative imaging, correct selection remains a challenge. With limited feedback during surgery, it is difficult to verify correct deployment. We propose the use of integrated impedance measurements and Electrical Impedance Tomography (EIT) imaging to assess the deformation of the balloon and determine the size and shape of the surrounding lumen. Previous work using single impedance measurements, or pressure data and analytical models, whilst demonstrating high sizing accuracy, have assumed a circular cross section. Here we extend these methods by adding a multitude of electrodes to detect elliptical and occluded lumen and obtain EIT images to localise deformations. Using a 14 Fr (5.3 mm) catheter as an example, numerical simulations were performed to find the optimal electrode configuration of two rings of 8 electrodes spaced 10 mm apart. The simulations predicted that the maximum detectable aspect ratio decreased from 0.9 for a 14mm balloon to 0.5 at 30mm. The sizing and ellipticity detection results were verified experimentally. A prototype robotic balloon catheter was constructed to automatically inflate a compliant balloon while simultaneously recording EIT and pressure data. Data were collected in experiments replicating stenotic vessels with an elliptical and asymmetrical profile, and the widening of a lumen during angioplasty. After calibration, the system was able to correctly localise the occlusion and detect aspect ratios of 0.75. EIT images further localised the occlusion and visualised the dilation of the lumen during balloon inflation

MicroCT optimisation for imaging fascicular anatomy in peripheral nerves

Due to the lack of understanding of the fascicular organisation, vagus nerve stimulation (VNS) leads to unwanted off-target effects. Micro-computed tomography (microCT) can be used to trace fascicles from periphery and image fascicular anatomy. In this study, we present a simple and reproducible method for imaging fascicles in peripheral nerves with iodine staining and microCT for the determination of fascicular anatomy and organisation

Patient-Specific 3D Printed Models for Education, Research and Surgical Simulation

3D printing techniques are increasingly used in engineering science, allowing the use of computer aided design (CAD) to rapidly and inexpensively create prototypes and components. There is also growing interest in the application of these techniques in a clinical context for the creation of anatomically accurate 3D printed models from medical images for therapy planning, research, training and teaching applications. However, the techniques and tools available to create 3D models of anatomical structures typically require specialist knowledge in image processing and mesh manipulation to achieve. In this book chapter we describe the advantages of 3D printing for patient education, healthcare professional education, interventional planning and implant development. We also describe how to use medical image data to segment volumes of interest, refine and prepare for 3D printing. We will use a lung as an example. The information in this section will allow anyone to create own 3D printed models from medical image data. This knowledge will be of use to anyone with little or no previous experience in medical image processing who have identified a potential application for 3D printing in a medical context, or those with a more general interest in the techniques

Non-invasive measurement of cholesterol in human blood by impedance technique: an investigation by 2D finite element field modelling

This paper concerns detection of solid particles suspended in conductive media by impedance technique. The technique is based on changes in impedance measured between two electrodes placed across a given volume of conducting medium. It presents a methodology for modelling and investigation of the feasibility of such a technique for particle detection by 2D finite element (FE) field modelling. This is based on modelling and computation of electric field distribution between the above electrodes. It establishes the modelling approach, the complexity involved and justifies the need for modelling in 3D to incorporate some of the effects that cannot be taken into account in 2D models. It reports on the modelling investigation for a specific case of detecting, by impedance technique cholesterol particles suspended in human blood and points to a possible instrument for non-invasive measurement of blood cholesterol level

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