Advanced digital electrical impedance tomography system for biomedical imaging

Electrical Impedance Tomography (EIT) images the spatial conductivity distribution in an electrode-bounded sensing domain by non-intrusively generating an electric field and measuring the induced boundary voltage. Since its emergence, it has attracted ample interest in the field of biomedical imaging owing to its fast, cost efficient, label-free and non-intrusive sensing ability. Well-investigated biomedical applications of the EIT include lung ventilation monitoring, breast cancer imaging, and brain function imaging. This thesis probes an emerging biomedical application of EIT in three dimensional (3D) cell culture imaging to study non-destructively the biological behaviour of a 3D cell culture system, on which occasion real-time qualitative and quantitative imaging are becoming increasingly desirable. Focused on this topic, the contribution of the thesis can be summarised from the perspectives of biomedical-designed EIT system, fast and effective image reconstruction algorithms, miniature EIT sensors and experimental studies on cell imaging and cell-drug response monitoring, as follows. First of all, in order to facilitate fast, broadband and real-time 3D conductivity imaging for biomedical applications, the design and evaluation of a novel multi-frequency EIT (mfEIT) system was presented. The system integrated 32 electrode interfaces and its working frequency ranged from 10 kHz to 1 MHz. Novel features of the system included: a) a fully adjustable multi-frequency current source with current monitoring function was designed; b) a flexible switching scheme together with a semi-parallel data acquisition architecture was developed for high-frame-rate data acquisition; c) multi-frequency simultaneous digital quadrature demodulation was accomplished, and d) a 3D imaging software, i.e. Visual Tomography, was developed to perform real-time two dimensional (2D) and 3D image reconstruction, visualisation and analysis. The mfEIT system was systematically tested and evaluated on the basis of the Signal to Noise Ratio (SNR), frame rate, and 2D and 3D multi-frequency phantom imaging. The highest SNR achieved by the system was 82.82 dB on a 16-electrode EIT sensor. The frame rate was up to 546 frames per second (fps) at serial mode and 1014 fps at semi-parallel mode. The evaluation results indicate that the presented mfEIT system is a powerful tool for real-time 2D and 3D biomedical imaging. The quality of tomographic images is of great significance for performing qualitative or quantitative analysis in biomedical applications. To realise high quality conductivity imaging, two novel image reconstruction algorithms using adaptive group sparsity constraint were proposed. The proposed algorithms considered both the underlying structure of the conductivity distribution and sparsity priors in order to reduce the degree of freedom and pursue solutions with the group sparsity structure. The global characteristic of inclusion boundaries was studied as well by imposing the total variation constraint on the whole image. In addition, two adaptive pixel grouping methods were also presented to extract the structure information without requiring any a priori knowledge. The proposed algorithms were evaluated comparatively through numerical simulation and phantom experiments. Compared with the state-of-the-art algorithms such as l1 regularisation, the proposed algorithms demonstrated superior spatial resolution and preferable noise reduction performance in the reconstructed images. These features were demanded urgently in biomedical imaging. Further, a planar miniature EIT sensor amenable to the standard 3D cell culture format was designed and a 3D forward model was developed for 3D imaging. A novel 3D-Laplacian and sparsity joint regularisation algorithm was proposed for enhanced 3D image reconstruction. Simulated phantoms with spheres located at different vertical and horizontal positions were imaged for 3D imaging performance evaluation. Image reconstructions of MCF-7 human breast cancer cell spheroids and triangular breast cancer cell pellets were carried out for experimental verification. The results confirmed that robust impedance measurement on the highly conductive cell culture medium was feasible and, greatly improved image quality was obtained by using the proposed regularisation method. Finally, a series of cancer cell spheroid imaging tests and real-time cell-drug response monitoring experiments by using the developed mfEIT system (Chapter 3), the designed miniature EIT sensors (Chapter 6) and the proposed image reconstruction algorithms (Chapter 4, 5 and 6) were carried out followed by comparative analysis. The stability of long-term impedance measurement on the highly conductive cell culture medium was verified firstly. Subsequently, by using the proposed algorithms in Chapter 4 and Chapter 5, high quality cancer cell spheroid imaging on a miniature sensor with 2D electrode configuration was achieved. Further, preliminary experiments on real-time monitoring of human breast cancer cell and anti-cancer drug response were performed and analysed. Promising results were obtained from these experiments. In summary, the work demonstrated in this thesis validated the feasibility of using the developed mfEIT system, the proposed image reconstruction algorithms, as well as the designed miniature EIT sensors to visualise 3D cell culture systems such as cell spheroids or artificial tissues and organs. The established work would expedite the real-time qualitative and quantitative imaging of 3D cell culture systems for the rapid assessment of cellular dynamics

High Resolution 3D Ultrasonic Breast Imaging by Time-Domain Full Waveform Inversion

Ultrasound tomography (UST) scanners allow quantitative images of the human breast's acoustic properties to be derived with potential applications in screening, diagnosis and therapy planning. Time domain full waveform inversion (TD-FWI) is a promising UST image formation technique that fits the parameter fields of a wave physics model by gradient-based optimization. For high resolution 3D UST, it holds three key challenges: Firstly, its central building block, the computation of the gradient for a single US measurement, has a restrictively large memory footprint. Secondly, this building block needs to be computed for each of the $10^3-10^4$ measurements, resulting in a massive parallel computation usually performed on large computational clusters for days. Lastly, the structure of the underlying optimization problem may result in slow progression of the solver and convergence to a local minimum. In this work, we design and evaluate a comprehensive computational strategy to overcome these challenges: Firstly, we introduce a novel gradient computation based on time reversal that dramatically reduces the memory footprint at the expense of one additional wave simulation per source. Secondly, we break the dependence on the number of measurements by using source encoding (SE) to compute stochastic gradient estimates. Also we describe a more accurate, TD-specific SE technique with a finer variance control and use a state-of-the-art stochastic LBFGS method. Lastly, we design an efficient TD multi-grid scheme together with preconditioning to speed up the convergence while avoiding local minima. All components are evaluated in extensive numerical proof-of-concept studies simulating a bowl-shaped 3D UST breast scanner prototype. Finally, we demonstrate that their combination allows us to obtain an accurate 442x442x222 voxel image with a resolution of 0.5mm using Matlab on a single GPU within 24h

Microwave Sensing and Imaging

In recent years, microwave sensing and imaging have acquired an ever-growing importance in several applicative fields, such as non-destructive evaluations in industry and civil engineering, subsurface prospection, security, and biomedical imaging. Indeed, microwave techniques allow, in principle, for information to be obtained directly regarding the physical parameters of the inspected targets (dielectric properties, shape, etc.) by using safe electromagnetic radiations and cost-effective systems. Consequently, a great deal of research activity has recently been devoted to the development of efficient/reliable measurement systems, which are effective data processing algorithms that can be used to solve the underlying electromagnetic inverse scattering problem, and efficient forward solvers to model electromagnetic interactions. Within this framework, this Special Issue aims to provide some insights into recent microwave sensing and imaging systems and techniques

Computational Electromagnetic Studies for Low-Frequency Compensation of the Reflector Impulse-Radiating Antenna

The reflector impulse-radiating antenna (IRA) is considered to meet the requirement for a wideband, directional antenna with short temporal response and small electrical footprint. Standard reflector IRA designs are modeled and performance is simulated using full-wave computational electromagnetic (CEM) software. Characterization of the standard designs reveals the possible existence of wide, frequency-independent backlobes containing nearly 40% of the radiated power at high frequencies. These undesirable backlobes have never been hypothesized, predicted or measured, likely due in part to their alignment outside the primary measurement planes. At the lowest operating frequencies, the reflector IRA is unaffected by backlobes, but is characterized by low radiation efficiency and high resistive losses. Simulated studies are conducted to identify options for enhancing the low-frequency performance of the reflector IRA, including novel multi-arm feed structures and varied resistor distributions and values in the matching circuit component of the antenna design. Both techniques are predicted to provide viable options for enhancing and tuning the performance of the reflector IRA at low frequencies

Proceedings of the 2022 Joint Workshop of Fraunhofer IOSB and Institute for Anthropomatics, Vision and Fusion Laboratory

In August 2022, Fraunhofer IOSB and IES of KIT held a joint workshop in a Schwarzwaldhaus near Triberg. Doctoral students presented research reports and discussed various topics like computer vision, optical metrology, network security, usage control, and machine learning. This book compiles the workshop\u27s results and ideas, offering a comprehensive overview of the research program of IES and Fraunhofer IOSB

A hybrid approach to determining cornea mechanical properties using a combination of inverse finite element analysis and experimental techniques

It is of great clinical importance to predict the behaviour of the cornea in various diseases and post-surgical recovery. Therefore, a numerical model that is able to simulate the corneal behaviour, considering corneal material properties obtained from individuals is highly desirable. In this work a combined numerical-experimental technique has been developed that can characterize the mechanical properties of a cornea properties from two aspects: time-dependency and spatial variation. Initially, an analysis of the material properties of porcine corneas was performed to investigate the time-dependent behaviour of the cornea. A simple stress relaxation test was used to determine the viscoelastic properties of a cornea and a rheological model was built based on the Generalized Maxwell (GM) approach. A validation experiment using nano-indentation showed that an isotropic GM model was insufficient for describing the corneal time-dependent behaviour when exposed to a complex stress state. A technique was proposed that takes into account the microstructural composition of the cornea and is based on a combination of nano-indentation experiment, isotropic and transversely isotropic numerical models, and an inverse finite element method. The good agreement using this method suggests that this is a promising technique for measuring the time-dependent properties of the cornea. The spatial variation of the properties was then investigated. This time, the long term structural response of the cornea was targeted. A full field displacement response of a loaded cornea was evaluated from Optical Coherence Tomography (OCT) volume reconstructions of the cornea using Digital Volume Correlation (DVC). The inverse finite element method was employed with two models sequentially; first, a radially partitioned model and then a circumferentially partitioned model, in order to recover the elastic parameters in radial and circumferential directions. The good agreement using this method suggests that this is a promising and reliable technique for identifying the distribution of the corneal properties. In this research, we have shown that it is possible to determine the local time-dependent properties of the cornea and the in-depth (2D) distribution of the properties using the hybrid technique. This technique has the potential to be implemented in vivo. However, further work should focus on the feasibility of this technique in practice

Applications of Mathematical Models in Engineering

The most influential research topic in the twenty-first century seems to be mathematics, as it generates innovation in a wide range of research fields. It supports all engineering fields, but also areas such as medicine, healthcare, business, etc. Therefore, the intention of this Special Issue is to deal with mathematical works related to engineering and multidisciplinary problems. Modern developments in theoretical and applied science have widely depended our knowledge of the derivatives and integrals of the fractional order appearing in engineering practices. Therefore, one goal of this Special Issue is to focus on recent achievements and future challenges in the theory and applications of fractional calculus in engineering sciences. The special issue included some original research articles that address significant issues and contribute towards the development of new concepts, methodologies, applications, trends and knowledge in mathematics. Potential topics include, but are not limited to, the following: Fractional mathematical models; Computational methods for the fractional PDEs in engineering; New mathematical approaches, innovations and challenges in biotechnologies and biomedicine; Applied mathematics; Engineering research based on advanced mathematical tools