Ultrahigh Field Functional Magnetic Resonance Electrical Impedance Tomography (fMREIT) in Neural Activity Imaging

abstract: A direct Magnetic Resonance (MR)-based neural activity mapping technique with high spatial and temporal resolution may accelerate studies of brain functional organization. The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution of fMRI is high. However, fMRI signals are highly influenced by the vasculature in each voxel and can be affected by capillary orientation and vessel size. Functional MRI analysis may, therefore, produce misleading results when voxels are nearby large vessels. Another problem in fMRI is that hemodynamic responses are slower than the neuronal activity. Therefore, temporal resolution is limited in fMRI. Furthermore, the correlation between neural activity and the hemodynamic response is not fully understood. fMRI can only be considered an indirect method of functional brain imaging. Another MR-based method of functional brain mapping is neuronal current magnetic resonance imaging (ncMRI), which has been studied over several years. However, the amplitude of these neuronal current signals is an order of magnitude smaller than the physiological noise. Works on ncMRI include simulation, phantom experiments, and studies in tissue including isolated ganglia, optic nerves, and human brains. However, ncMRI development has been hampered due to the extremely small signal amplitude, as well as the presence of confounding signals from hemodynamic changes and other physiological noise. Magnetic Resonance Electrical Impedance Tomography (MREIT) methods could have the potential for the detection of neuronal activity. In this technique, small external currents are applied to a body during MR scans. This current flow produces a magnetic field as well as an electric field. The altered magnetic flux density along the main magnetic field direction caused by this current flow can be obtained from phase images. When there is neural activity, the conductivity of the neural cell membrane changes and the current paths around the neurons change consequently. Neural spiking activity during external current injection, therefore, causes differential phase accumulation in MR data. Statistical analysis methods can be used to identify neuronal-current-induced magnetic field changes.Dissertation/ThesisDoctoral Dissertation Biomedical Engineering 201

DICOM for EIT

With EIT starting to be used in routine clinical practice [1], it important that the clinically relevant information is portable between hospital data management systems. DICOM formats are widely used clinically and cover many imaging modalities, though not specifically EIT. We describe how existing DICOM specifications, can be repurposed as an interim solution, and basis from which a consensus EIT DICOM ‘Supplement’ (an extension to the standard) can be writte

Estimation of thorax shape for forward modelling in lungs EIT

The thorax models for pre-term babies are developed based on the CT scans from new-borns and their effect on image reconstruction is evaluated in comparison with other available models

Rapid generation of subject-specific thorax forward models

For real-time monitoring of lung function using accurate patient geometry, shape information needs to be acquired and a forward model generated rapidly. This paper shows that warping a cylindrical model to an acquired shape results in meshes of acceptable mesh quality, in terms of stretch and aspect ratio

Torso shape detection to improve lung monitoring

Two methodologies are proposed to detect the patient-specific boundary of the chest, aiming to produce a more accurate forward model for EIT analysis. Thus, a passive resistive and an inertial prototypes were prepared to characterize and reconstruct the shape of multiple phantoms. Preliminary results show how the passive device generates a minimum scatter between the reconstructed image and the actual shap

Nanoparticle electrical impedance tomography

We have developed a new approach to imaging with electrical impedance tomography (EIT) using gold nanoparticles (AuNPs) to enhance impedance changes at targeted tissue sites. This is achieved using radio frequency (RF) to heat nanoparticles while applying EIT imaging. The initial results using 5-nm citrate coated AuNPs show that heating can enhance the impedance in a solution containing AuNPs due to the application of an RF field at 2.60 GHz

Imaging fast neural activity in the brain with Electrical Impedance Tomography

Electrical impedance tomography (EIT) is an emerging medical imaging technique that can be employed to reconstruct the internal conductivity of an object from measurements made on the boundary. One proposed application for EIT is in head imaging, including imaging of impedance changes that occur with neuronal depolarisation and the imaging of acute stroke. The work of this thesis was aimed at advancing the imaging of brain pathology and function, with particular focus on the imaging of fast neural activity. Chapter 1 is a review of other brain imaging techniques, the principles of bioimpedance and EIT, and of previous impedance recordings of fast neural activity. Chapter 2 was a comparison of reconstruction algorithms for the detection of acute stroke using EIT in a realistic head-shaped tank, which entailed assessing boundary voltage rejection methods and quantitative analysis of image quality to determine the best reconstruction algorithms for the detection of acute stroke. In chapter 3, an EIT imaging dataset of fast neural activity, previously collected in a rat model, was assessed using second-level statistical parametric mapping (SPM) and the spatio-temporal propagation of the activity assessed and compared to the neurophysiological literature, which was reviewed in chapter 1. The analysis undertaken in chapter 3 illustrated some key methodological issues, which were addressed in chapter 4: new high resolution meshes and better optimised matrix inversion were employed, a new algorithm for electrode alignment was developed, also the use of SPM was validated by applying it to control datasets and through the use of statistical non-parametric mapping. Chapters 5 and 6 detail work attempting to cross-validate the use of EIT to image fast neural activity by employing a physiological stimulus, mechanical whisker displacement, and comparing the findings to other neurophysiological techniques recorded in the same model. Chapter 5 details work to validate the model and the impedance findings in this model as compared to previously published neurophysiological results, while chapter 6 details the use of other neurophysiological techniques for cross-validation

Validation of Transcranial Electrical Stimulation (TES) Finite Element Modeling Against MREIT Current Density Imaging in Human Subjects

abstract: Transcranial electrical stimulation (tES) is a non-invasive brain stimulation therapy that has shown potential in improving motor, physiological and cognitive functions in healthy and diseased population. Typical tES procedures involve application of weak current (< 2 mA) to the brain via a pair of large electrodes placed on the scalp. While the therapeutic benefits of tES are promising, the efficacy of tES treatments is limited by the knowledge of how current travels in the brain. It has been assumed that the current density and electric fields are the largest, and thus have the most effect, in brain structures nearby the electrodes. Recent studies using finite element modeling (FEM) have suggested that current patterns in the brain are diffuse and not concentrated in any particular brain structure. Although current flow modeling is useful means of informing tES target optimization, few studies have validated tES FEM models against experimental measurements. MREIT-CDI can be used to recover magnetic flux density caused by current flow in a conducting object. This dissertation reports the first comparisons between experimental data from in-vivo human MREIT-CDI during tES and results from tES FEM using head models derived from the same subjects. First, tES FEM pipelines were verified by confirming FEM predictions agreed with analytic results at the mesh sizes used and that a sufficiently large head extent was modeled to approximate results on human subjects. Second, models were used to predict magnetic flux density, and predicted and MREIT-CDI results were compared to validate and refine modeling outcomes. Finally, models were used to investigate inter-subject variability and biological side effects reported by tES subjects. The study demonstrated good agreements in patterns between magnetic flux distributions from experimental and simulation data. However, the discrepancy in scales between simulation and experimental data suggested that tissue conductivities typically used in tES FEM might be incorrect, and thus performing in-vivo conductivity measurements in humans is desirable. Overall, in-vivo MREIT-CDI in human heads has been established as a validation tool for tES predictions and to study the underlying mechanisms of tES therapies.Dissertation/ThesisDoctoral Dissertation Biomedical Engineering 201

Imaging fascicular organisation in mammalian vagus nerve for selective VNS

Nerves contain a large number of nerve fibres, or axons, organised into bundles known as fascicles. Despite the somatic nervous system being well understood, the organisation of the fascicles within the nerves of the autonomic nervous system remains almost completely unknown. The new field of bioelectronics medicine, Electroceuticals, involves the electrical stimulation of nerves to treat diseases instead of administering drugs or performing complex surgical procedures. Of particular interest is the vagus nerve, a prime target for intervention due to its afferent and efferent innervation to the heart, lungs and majority of the visceral organs. Vagus nerve stimulation (VNS) is a promising therapy for treatment of various conditions resistant to standard therapeutics. However, due to the unknown anatomy, the whole nerve is stimulated which leads to unwanted off-target effects. Electrical Impedance Tomography (EIT) is a non-invasive medical imaging technique in which the impedance of a part of the body is inferred from electrode measurements and used to form a tomographic image of that part. Micro-computed tomography (microCT) is an ex vivo method that has the potential to allow for imaging and tracing of fascicles within experimental models and facilitate the development of a fascicular map. Additionally, it could validate the in vivo technique of EIT. The aim of this thesis was to develop and optimise the microCT imaging method for imaging the fascicles within the nerve and to determine the fascicular organisation of the vagus nerve, ultimately allowing for selective VNS. Understanding and imaging the fascicular anatomy of nerves will not only allow for selective VNS and the improvement of its therapeutic efficacy but could also be integrated into the study on all peripheral nerves for peripheral nerve repair, microsurgery and improving the implementation of nerve guidance conduits. Chapter 1 provides an introduction to vagus nerve anatomy and the principles of microCT, neuronal tracing and EIT. Chapter 2 describes the optimisation of microCT for imaging the fascicular anatomy of peripheral nerves in the experimental rat sciatic and pig vagus nerve models, including the development of pre-processing methods and scanning parameters. Cross-validation of this optimised microCT method, neuronal tracing and EIT in the rat sciatic nerve was detailed in Chapter 3. Chapter 4 describes the study with microCT with tracing, EIT and selective stimulation in pigs, a model for human nerves. The microCT tracing approach was then extended into the subdiaphragmatic branches of the vagus nerves, detailed in Chapter 5. The ultimate goal of human vagus nerve tracing was preliminarily performed and described in Chapter 6. Chapter 7 concludes the work and describes future work. Lastly, Appendix 1 (Chapter 8) is a mini review on the application of selective vagus nerve stimulation to treat acute respiratory distress syndrome and Appendix 2 is morphological data corresponding to Chapter 4

Biomedical Engineering

Biomedical engineering is currently relatively wide scientific area which has been constantly bringing innovations with an objective to support and improve all areas of medicine such as therapy, diagnostics and rehabilitation. It holds a strong position also in natural and biological sciences. In the terms of application, biomedical engineering is present at almost all technical universities where some of them are targeted for the research and development in this area. The presented book brings chosen outputs and results of research and development tasks, often supported by important world or European framework programs or grant agencies. The knowledge and findings from the area of biomaterials, bioelectronics, bioinformatics, biomedical devices and tools or computer support in the processes of diagnostics and therapy are defined in a way that they bring both basic information to a reader and also specific outputs with a possible further use in research and development