Basic study of a diagnostic modality employing a new electrical impedance tomography (EIT) method for noninvasive measurement in localized tissue

The objective of this study is to develop a device for noninvasive local tissue electrical impedance tomography (EIT) using divided electrodes with guard electrodes and to validate its effectiveness using bioequivalent phantoms. For this purpose, we prepared a measurement device and bioequivalent phantoms, measured the electrical characteristics of the phantoms, and validated the method using the phantoms. Monolayer phantoms mimicking the brain and muscle and bilayer phantoms consisting of muscle and brain layers were prepared. The relative differences between the measured electrical conductivities of the monolayer brain and muscle phantoms and the true values determined by the 4-electrode method were both less than 10%. The relative differences between the measured and true values in the bilayer phantoms were less than 20% in both layers. The biological impedance measurement device that we developed was confirmed to be effective for impedance measurement in bilayer phantoms with different electrical impedances. To develop a device for the early diagnosis of breast diseases, the development of a multi-layer phantom and demonstration of the effectiveness of the device for its examination are necessary. If the device that we developed makes impedance measurement in breast tumors possible, it may be used as a new diagnostic modality for breast diseases

Photonic Biosensors: Detection, Analysis and Medical Diagnostics

The role of nanotechnologies in personalized medicine is rising remarkably in the last decade because of the ability of these new sensing systems to diagnose diseases from early stages and the availability of continuous screenings to characterize the efficiency of drugs and therapies for each single patient. Recent technological advancements are allowing the development of biosensors in low-cost and user-friendly platforms, thereby overcoming the last obstacle for these systems, represented by limiting costs and low yield, until now. In this context, photonic biosensors represent one of the main emerging sensing modalities because of their ability to combine high sensitivity and selectivity together with real-time operation, integrability, and compatibility with microfluidics and electric circuitry for the readout, which is fundamental for the realization of lab-on-chip systems. This book, “Photonic Biosensors: Detection, Analysis and Medical Diagnostics”, has been published thanks to the contributions of the authors and collects research articles, the content of which is expected to assume an important role in the outbreak of biosensors in the biomedical field, considering the variety of the topics that it covers, from the improvement of sensors’ performance to new, emerging applications and strategies for on-chip integrability, aiming at providing a general overview for readers on the current advancements in the biosensing field

Review on electrical impedance tomography: Artificial intelligence methods and its applications

© 2019 by the authors. Electrical impedance tomography (EIT) has been a hot topic among researchers for the last 30 years. It is a new imaging method and has evolved over the last few decades. By injecting a small amount of current, the electrical properties of tissues are determined and measurements of the resulting voltages are taken. By using a reconstructing algorithm these voltages then transformed into a tomographic image. EIT contains no identified threats and as compared to magnetic resonance imaging (MRI) and computed tomography (CT) scans (imaging techniques), it is cheaper in cost as well. In this paper, a comprehensive review of efforts and advancements undertaken and achieved in recent work to improve this technology and the role of artificial intelligence to solve this non-linear, ill-posed problem are presented. In addition, a review of EIT clinical based applications has also been presented

The application of biomedical engineering techniques to the diagnosis and management of tropical diseases: A review

This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications

Doctor of Philosophy

dissertationDriven by a myriad of potential applications such as communications, medical imaging, security, spectroscopy, and so on, terahertz (THz) technology has emerged as a rapidly growing technological field during the last three decades. However, since conventional materials typically used in microwave and optical frequencies are lossy or do not effectively respond at these frequencies, it is essential to find or develop novel materials that are suitable for device applications in the THz range. Therefore, there is wide interest in the community in employing novel naturally-occurring materials, such as 2D materials, as well as in designing artificial metamaterial structures for THz applications. Here, we combined both of these approaches so to develop reconfigurable THz devices capable of providing amplitude modulation, phase modulation, and resonance frequency tuning. First, graphene is employed as the reconfigurable element in metamaterial phase modulators. For this purpose, we propose the use of unit cells with deep-subwavelength dimensions, which can have multiple advantaged for beam shaping applications. The analyzed metamaterials have one of the smallest unit cell to wavelength ratios reported or proposed todate at THz frequencies. By systematic analysis of the geometrical tradeoffs in these devices it is found that there is an optimal unit cell dimension, corresponding roughly to ~λ/20, which can deliver the best performance. In addition to this, we explored other applications of graphene in metamaterial devices, including amplitude modulation and resonance-shifting. These studies motivated us to analyze what is the most suitable role of graphene from a THz device perspective: is graphene a good plasmonic material? Or it is better suited as a reconfigurable material providing tunability to otherwise passive metallic structures? Our studies show that the Drude scattering time in graphene is an important parameter in this regard. In order to attain strong plasmonic resonances graphene samples with τ >> 1ps are required, which is challenging in large area CVD samples. But graphene is just one example of a wider class of 2D materials. In this work we also studied for the first time the application of 2D materials beyond graphene as reconfigurable elements in THz devices. For this purpose, Molybdenum Disulfide (MoS2) was employed as the reconfigurable element in cross-slot metamaterial amplitude modulators. Our results evidence that smaller insertion loss is possible when employing 2D materials with a bandgap, such as MoS2, rather than a zero-gap material such as graphene. Furthermore, because of a stronger optical absorption active control of the metamaterial properties is possible by altering the intensity of an optical pump. We later investigate and discuss transparent conductive oxides (TCOs), which constitute an interesting choice for developing visible-transparent THz-functional metamaterial devices for THz applications. These materials show a metallic THz response and thus can substitute the metal patterns in metamaterial devices. In our particular studies we analyzed samples consisting of: (i) two-dimensional electron gases at the interface between polar/nonpolar complex oxides having record-high electron density, and (ii) thin-films of La-doped BaSnO3 having record-high conductivity in a TCO. These materials exhibit a flat THz conductivity across a broad terahertz frequency window. As a result of their metal-like broadband THz response, we demonstrate a visible-transparent THz-functional electromagnetic structure consisting of a wire-grid polarizer

Incorporation of anisotropic conductivities in EEG source analysis

The electroencephalogram (EEG) is a measurement of brain activity over a period of time by placing electrodes at the scalp (surface EEG) or in the brain (depth EEG) and is used extensively in the clinical practice. In the past 20 years, EEG source analysis has been increasingly used as a tool in the diagnosis of neurological disorders (like epilepsy) and in the research of brain functionality. EEG source analysis estimates the origin of brain activity given the electrode potentials measured at the scalp. This involves solving an inverse problem where a forward solution, which depends on the source parameters, is fitted to the given set of electrode potentials. The forward solution are the electrode potentials caused by a source in a given head model. The head model is dependent on the geometry and the conductivity. Often an isotropic conductivity (i.e. the conductivity is equal in all directions) is used, although the skull and white matter have an anisotropic conductivity (i.e. the conductivity can differ depending on the direction the current flows). In this dissertation a way to incorporate the anisotropic conductivities is presented and the effect of not incorporating these anisotropic conductivities is investigated. Spherical head models are simple head models where an analytical solution to the forward problem exists. A small simulation study in a 5 shell spherical head model was performed to investigate the estimation error due to neglecting the anisotropic properties of skull and white matter. The results show that the errors in the dipole location can be larger than 15 mm, which is unacceptable for an accurate dipole estimation in the clinical practice. Therefore, anisotropic conductivities have to be included in the head model. However, these spherical head models are not representative for the human head. Realistic head models are usually made from magnetic resonance scans through segmentation and are a better approximation to the geometry of the human head. To solve the forward problem in these head models numerical methods are needed. In this dissertation we proposed a finite difference technique that can incorporate anisotropic conductivities. Moreover, by using the reciprocity theorem the forward calculation time during an dipole source estimation procedure can be significantly reduced. By comparing the analytical solution for the dipole estimation problem with the one using the numerical method, the anisotropic finite difference with reciprocity method (AFDRM) is validated. Therefore, a cubic grid is made on the 5 shell spherical head model. The electrode potentials are obtained in the spherical head model with anisotropic conductivities by solving the forward problem using the analytical solution. Using these electrode potentials the inverse problem was solved in the spherical head model using the AFDRM. In this way we can determine the location error due to using the numerical technique. We found that the incorporation of anisotropic conductivities results in a larger location error when the head models are fully isotropical conducting. Furthermore, the location error due to the numerical technique is smaller if the cubic grid is made finer. To minimize the errors due to the numerical technique, the cubic grid should be smaller than or equal to 1 mm. Once the numerical technique is validated, a realistic head model can now be constructed. As a cubic grid should be used of at most 1 mm, the use of segmented T1 magnetic resonance images is best suited the construction. The anisotropic conductivities of skull and white matter are added as follows: The anisotropic conductivity of the skull is derived by calculating the normal and tangential direction to the skull at each voxel. The conductivity in the tangential direction was set 10 times larger than the normal direction. The conductivity of the white matter was derived using diffusion weighted magnetic resonance imaging (DW-MRI), a technique that measures the diffusion of water in several directions. As diffusion is larger along the nerve fibers, it is assumed that the conductivity along the nerve fibers is larger than the perpendicular directions to the nerve bundle. From the diffusion along each direction, the conductivity can be derived using two approaches. A simplified approach takes the direction with the largest diffusion and sets the conductivity along that direction 9 times larger than the orthogonal direction. However, by calculating the fractional anisotropy, a well-known measure indicating the degree of anisotropy, we can appreciate that a fractional anisotropy of 0.8715 is an overestimation. In reality, the fractional anisotorpy is mostly smaller and variable throughout the white matter. A realistic approach was therefore presented, which states that the conductivity tensor is a scaling of the diffusion tensor. The volume constraint is used to determine the scaling factor. A comparison between the realistic approach and the simplified approach was made. The results showed that the location error was on average 4.0 mm with a maximum of 10 mm. The orientation error was found that the orientation could range up to 60 degrees. The large orientation error was located at regions where the anisotropic ratio was low using the realistic approach but was 9 using the simplified approach. Furthermore, as the DW-MRI can also be used to measure the anisotropic diffusion in a gray matter voxel, we can derive a conductivity tensor. After investigating the errors due to neglecting these anisotropic conductivities of the gray matter, we found that the location error was very small (average dipole location error: 2.8 mm). The orientation error was ranged up to 40 degrees, although the mean was 5.0 degrees. The large errors were mostly found at the regions that had a high anisotropic ratio in the anisotropic conducting gray matter. Mostly these effects were due to missegmentation or to partial volume effects near the boundary interfaces of the gray and white matter compartment. After the incorporation of the anisotropic conductivities in the realistic head model, simulation studies can be performed to investigate the dipole estimation errors when these anisotropic conductivities of the skull and brain tissues are not taken into account. This can be done by comparing the solution to the dipole estimation problem in a head model with anisotropic conductivities with the one in a head model, where all compartments are isotropic conducting. This way we determine the error when a simplified head model is used instead of a more realistic one. When the anisotropic conductivity of both the skull and white matter or the skull only was neglected, it was found that the location error between the original and the estimated dipole was on average, 10 mm (maximum: 25 mm). When the anisotropic conductivity of the brain tissue was neglected, the location error was much smaller (an average location error of 1.1 mm). It was found that the anisotropy of the skull acts as an extra shielding of the electrical activity as opposed to an isotropic skull. Moreover, we saw that if the dipole is close to a highly anisotropic region, the potential field is changed reasonable in the near vicinity of the location of the dipole. In reality EEG contains noise contributions. These noise contribution will interact with the systematical error by neglecting anisotropic conductivities. The question we wanted to solve was “Is it worthwhile to incorporate anisotropic conductivities, even if the EEG contains noise?” and “How much noise should the EEG contain so that incorporating anisotropic conductivities improves the accuracy of EEG source analysis?”. When considering the anisotropic conductivities of the skull and brain tissues and the skull only, the location error due to the noise and neglecting the anisotropic conductivities is larger then the location error due to noise only. When only neglecting the anisotropic conductivities of the brain tissues only, the location error due to noise is similar to the location error due to noise and neglecting the anisotropic conductivities. When more advanced MR techniques can be used a better model to construct the anisotropic conductivities of the soft brain tissues can be used, which could result in larger errors even in the presence of noise. However, this is subject to further investigation. This suggests that the anisotropic conductivities of the skull should be incorporated. The technique presented in the dissertation can be used to epileptic patients in the presurgical evaluation. In this procedure patients are evaluated by means of medical investigations to determine the cause of the epileptic seizures. Afterwards, a surgical procedure can be performed to render the patient seizure free. A data set from a patiënt was obtained from a database of the Reference Center of Refractory Epilepsy of the Department of Neurology and the Department of Radiology of the Ghent University Hospital (Ghent, Belgium). The patient was monitored with a video/EEG monitoring with scalp and with implanted depth electrodes. An MR image was taken from the patient with the implanted depth electrodes, therefore, we could pinpoint the hippocampus as the onset zone of the epileptic seizures. The patient underwent a resective surgery removing the hippocampus, which rendered the patient seizure free. As DW-MRI images were not available, the head model constructed in chapter 4 and 5 was used. A neuroradiologist aligned the hippocampus in the MR image from which the head model was constructed. A spike was picked from a dataset and was used to estimate the source in a head model where all compartments were isotropic conducting, on one hand, and where the skull and brain tissues were anisotropic conducting, on the other. It was found that using the anisotropic head model, the source was estimated closer to the segmented hippocampus than the isotropic head model. This example shows the possibilities of this technique and allows us to apply it in the clinical practice. Moreover, a thorough validation of the technique has yet to be performed. There is a lot of discussion in the clinical community whether the spikes and epileptical seizures originate from the same origin in the brain. This question can be solved by applying our technique in patient studies

Analysis of crosstalk signals in a cylindrical layered volume conductor – Influence of the anatomy, detection system and physical properties of the tissues

A comparison of the ability of different spatial filters to reduce the amount of crosstalk in a surface electromyography (sEMG) measurement was conducted. It focused on the influence of different properties of the muscle anatomy and detection system used on the amount of crosstalk present in the measurements. An analytical model was developed which enabled the simulation of single fibre action potentials (SFAPs). These fibres were grouped together in motor units (MUs). Each MU has characteristics which, along with the SFAPs, are used to obtain the motor unit action potential (MUAP). A summation of the MUAPs from all the MUs in a muscle leads to the electromyogram (EMG) signal generated by the muscle. This is the first model which simulates a complete muscle for crosstalk investigation. Previous studies were done for single fibres (Farina&Rainoldi 1999; Farina et al. 2002e; Farina et al. 2004a) or MUs (Dimitrova et al. 2002; Dimitrov et al. 2003; Winter et al. 1994). Lowery et al. simulated a complete muscle, but only investigated one spatial filter (Lowery et al. 2003a). This model is thus the first of its kind. EMG signals were generated for limbs with different anatomical properties and recorded with various detection systems. The parameters used for comparison of the recorded signals are the average rectified value (ARV) and mean frequency (MNF), which describe the amplitude and frequency components of an EMG signal, respectively. These parameters were computed for each EMG signal and interpreted to make recommendations on which detection system results in the best crosstalk rejection for a specific experimental set-up. The conclusion is that crosstalk selectivity in an sEMG measurement is decreased by increasing the thickness of the fat layer, increasing the skin conductivity, decreasing the fibre length, increasing the interelectrode distance of the detection system, placing the detection electrodes directly above the end-plate area or an increased state of muscle contraction. Varying the contraction force strength or placing the detection electrodes directly above the tendon area has no influence on the crosstalk selectivity. For most of the conditions investigated, the normal double differential (NDD) detection system results in the best crosstalk reduction. The only exceptions are a set-up with poor skin conductivity where NDD and double differential (DD) performed comparably, and the two simulations in which the muscle length is varied, where the DD filter performed best. Previous studies have found DD to be more selective for crosstalk rejection than NDD (Dimitrov et al. 2003; Farina et al. 2002a; Van Vlugt&Van Dijk 2000). Possible reasons for the contradictory results are the high value of skin conductivity currently used or influences of the muscle geometry.Dissertation (MEng(Bio-Engineering))--University of Pretoria, 2007.Electrical, Electronic and Computer Engineeringunrestricte

Advances in Assistive Electronic Device Solutions for Urology

Recent technology advances have led urology to become one of the leading specialities to utilise novel electronic systems to manage urological ailments. Contemporary bladder management strategies such as urinary catheters can provide a solution but leave the user mentally and physically debilitated. The unique properties of modern electronic devices, i.e., flexibility, stretchability, and biocompatibility, have allowed a plethora of new technologies to emerge. Many novel electronic device solutions in urology have been developed for treating impaired bladder disorders. These disorders include overactive bladder (OAB), underactive bladder (UAB) and other-urinary-affecting disorders (OUAD). This paper reviews common causes and conservative treatment strategies for OAB, UAB and OUAD, discussing the challenges and drawbacks of such treatments. Subsequently, this paper gives insight into clinically approved and research-based electronic advances in urology. Advances in this area cover bladder-stimulation and -monitoring devices, robot-assistive surgery, and bladder and sphincter prosthesis. This study aims to introduce the latest advances in electronic solutions for urology, comparing their advantages and disadvantages, and concluding with open problems for future urological device solutions

Quality assurance guidelines for superficial hyperthermia clinical trials: II. Technical requirements for heating devices

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle

Estruturas tridimensionais eletro-estimuláveis à base de nanoestruturas de carbono/hidrogel para engenharia de tecido neuronal

The main objective of the present work consists of the optimization of the production of three-dimensional electro-responsive carbon-reinforced hydrogels, to study their cytocompatibility with neural stem cells (NSCs) for neural tissue engineering. For that matter, initially vertically aligned carbon nanotubes (VA-CNTs) with two different patterns were prepared by thermal chemical vapor deposition (T-CVD): (1) VA-CNTs dense forest and (1) VA-CNTs micropillars. Furthermore, the substrates previously described were studied after acetone vapor treatment, resulting in a cellular and “flower-like” pattern morphology, respectively. Structural characterization of the respective samples was made using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and the measurement of the water contact angle (WCA). The integration with gelatinmethacryloyl (GelMA) -based hydrogels were explored in the different studied samples. The influence of the different VA-CNTs prepared patterns was studied by the evaluation of the cell behavior with resort to NSCs. By immunocytochemical staining, cell viability assays and SEM, it was observed the cells affinity for the diverse carbon structures, in comparison to the silicon (Si) substrate. Besides, it was also verified the suitability of the VA-CNTs platforms for cell viability and proliferation. The collapsed VA-CNTs substrate made evident the tendency for cell differentiation into neurons, possibly due to their superficial roughness at the nanoscale, which favors this biological mechanism. The results obtained demonstrated that VA-CNTs based structures favors the proliferation and differentiation of NSCs, making them promising as future threedimensional electroresponsive structures with excellent performances for neural tissue engineering.O principal objetivo do presente trabalho constituiu na otimização da produção de estruturas tridimensionais eletro-estimuláveis à base de nanoestruturas de carbono/hidrogel, estudando a sua citocompatibilidade com células estaminais para engenharia de tecido neuronal. Nesse sentido foram primeiramente preparados dois padrões de nanotubos de carbono verticalmente alinhados (VA-CNTs) por deposição química em fase vapor (T-CVD): (1) floresta densa de VA-CNTs e (2) micropilares de VA-CNTs. Além disso, foram também estudados os substratos anteriormente descritos após tratamento por vapor de acetona, resultando na formação de VA-CNTs e micropadrões colapsados, apresentando uma morfologia com um padrão celular e uma semelhante a uma "flor", respetivamente. As respetivas amostras foram caracterizadas por microscopia eletrónica de varrimento (SEM), de transmissão (TEM) e foi medido o ângulo de contacto com a água (WCA). As diferentes amostras estudadas foram exploradas na integração com hidrogéis à base de gelatina metacrilada (GelMA). A influência dos diferentes padrões de VA-CNTs preparados foi estudada através da avaliação do comportamento celular com o recurso a células estaminais neurais (NSCs). Por ensaios de imunocitoquímica, viabilidade celular e SEM, foi observada a afinidade das células para com as diversas estruturas de carbono, em comparação com o substrato de silício (Si). Para além disso foi também verificada a aptidão das diversas estruturas baseadas em VA-CNTs como plataformas para proliferação e diferenciação de NSCs. Os substratos de VA-CNTs colapsados evidenciaram uma propensão para induzir a diferenciação celular em neurónios, possivelmente devido à sua rugosidade superficial à nanoescala favorecer este mecanismo biológico. Os resultados obtidos demonstraram que as estruturas baseadas em VA-CNTs favorecem a proliferação e diferenciação das células estaminais neurais, podendo futuramente ser aplicados como estruturas tridimensionais eletroestimuláveis com elevado desempenho para engenharia de tecido neural.Mestrado em Materiais e Dispositivos Biomédico