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

Assesment and optimisation techniques for an electrical impedance mammography system

Breast cancer detection through the use of Electrical Impedance Tomography (EIT) has been proposed for a number of years. Typically in an EIT or when in use in breast cancer detection, Electrical Impedance Mammography (EIM) system, the patient interface is that of electrodes. Positive and negative sinusoidal signals are injected into a patient multiple times at multiple frequencies, recording the developed surface voltages that naturally develop from the impedance of the body. A 2D or 3D reconstruction and visualisation of the impedance distribution is possible through the use of the recorded voltage amplitude and phase. Higher resolution images are achieved through higher electrode density (i.e.smaller electrode distance). Furthermore, tissue has a characteristic frequency response,which can be recorded if different injection frequencies are utilised. The higher thefrequency, the deeper the signal can penetrate into tissue and deeper through the cellular structures, potentially leading to tissue characterisation through its frequency response. Our group has suggested a unique combined EIT and ultrasound multimodal imaging system to detect breast cancer. This will use an EIT system to initially scan the breast,combining this parametric data with the high-resolution images of ultrasound to give a more accurate diagnosis. The prototype, known as V2, was functional but performed poorly, especially with respect to the signal to noise ratio. Images generated with this system were unclear. My role within the group was to analyze the performance of the V2 system and research best practice methods to improve the existing design, taking into consideration the intricacies of EIT hardware design and the targeted application. The improvements I suggested were incorporated into the V3 system, which was then compared with the V2 system, and showed significant performance improvement

Further investigation of a contactless patient-electrode interface of an Electrical Impedance Mammography system

The Sussex Mk4 Electrical Impedance Mammography (EIM) system is a novel instrument, designed for the detection of early breast cancer, based upon Electrical Impedance Tomography (EIT). Many innovations in the field have been incorporated in the design improving both signal distribution and response. This paper investigates the behaviour of the contactless patient-electrode interface. The interface was studied in detail using phantom and healthy volunteer, in-vivo, data. Our findings show the necessity for the careful design of electrode enclosure so that the response of the system is not affected by the unpredictable positioning of the breast; it closely mimics those conditions seen when using the phantom. The paper includes a number of possible designs and their individual characteristics. In addition an explanation on the unanticipated effects and solutions for such are described. © 2010 IOP Publishing Ltd

Detection of breast cancer with electrical impedance mammography

Electrical Impedance Tomography (EIT) is a medical imaging technique that reconstructs internal electrical conductivity distribution of a body from impedance data that is measured on the body surface, and Electrical Impedance Mammography (EIM) is the technique that applies EIT in breast cancer detection. The use of EIM for breast cancer identification is highly desirable because it is a non-invasive and low-cost imaging technology. EIM has the potential in detecting early stage cancer, however there are still challenges that hindering EIM to be provided as a routine health care system. There are three major groups of obstacles. One is the hardware design, which includes the selection of electronic components, electrode-skin contacting methods, etc. Second is theoretical problems such as electrode configurations, image reconstruction and regularization methods. Third is the development of analysis methods and generation of a cancerous tissue database. Research reported in this thesis strives to understand these problems and aims to provide possible solutions to build a clinical EIM system. The studies are carried out in four parts. First the functionalities of the Sussex Mk4 EIM system have been studied. Sensitivity of the system was investigated to find out the strength and weakness of the system. Then work has been made on image reconstruction and regularization methods in order to enhance the system’s endurance to noise, also to balance the reconstruction conductivity distribution throughout the reconstructed object. Then a novel cancer diagnosis technique was proposed. It was developed based on the electrical property of human breast tissue and the behaviour or systematic noise, to provide repeatable results for each patient. Finally evaluation has been made on previous EIM systems to find out the major problems. Based on sensitivity analysis, an optimal combined electrode configuration has been proposed to improve sensitivity. The system has been developed and produced meaningful clinical images. The work makes significant contributions to society. This novel cancer diagnosis method has high accuracy for cancer identification. The combined electrode configuration has also provided flexibilities in the designing of current driving and voltage receiving patterns, thus sensitivity of the EIM system can be greatly improved

Electrical impedance mammography : the key to low-cost, portable and non-invasive breast cancer screening?

Breast cancer is a major public health problem with 1.7 million cases diagnosed per year and is the leading cause of cancer deaths in women worldwide (Siegel, Miller & Jemal, 2016). The two main determinants of survival are early detection and optimal treatment. Despite the advances in medicine, breast cancer is detected at advanced stages in developing countries (DCs) because early detection, diagnosis and treatment cannot be efficiently promoted. Thus, disease burden is particularly high in DCs, where more than half of breast cancer cases and 62% of the deaths now occur. The “Breast Health Global Initiative” (BHGI) evaluated the complexity of healthcare systems in relation to breast cancer. Specifically, at the basic level, breast self- examination is encouraged, whereas diagnostic ultrasound and X-ray mammography are available at a limited level. At the increased level, patients have access to diagnostic mammography with opportunistic breast screening, and at a maximum level, the population undergoes organized screening for breast cancer (Anderson et al., 2006).peer-reviewe

Stimulation and measurement patterns versus prior information for fast 3D EIT: A breast screening case study

Imposing prior information is a typical strategy in inverse problems in return for a stable numerical algorithm. For a given imaging system configuration, Picard's stability condition could be deployed as a practical measure of the performance of the system against various priors and noise contaminated measurements. Herein, we make extensive use of this measure to quantify the performance of impedance imaging systems for various injection patterns. In effect, we numerically demonstrate that by varying electrode distributions and numbers, little improvement, if any, in the performance of the impedance imaging system is recorded. In contrast, by using groups of electrodes in the 3D current injection process, a step increase in performance is obtained. Numerical results on a female breast phantom reveal that the performance measure of the imaging system is 15% for a conventional combination of stimulation and prior information, 61% for groups of electrodes and the same prior and 97% for groups of electrodes and a more accurate prior. Finally, since a smaller number of electrodes is involved in the measurement process, a smaller number of measurements is acquired. However, no compromise in the quality of the reconstructed images is observed

Combining Multiple Boundary Shapes in Deformable EIT a Potential Use in Breast Imaging

A few emerging medical imaging methods are being developed for breast imaging. Electrical impedance tomography (EIT) is an excellent candidate for safe, low cost, and noninvasive breast cancer monitoring. Despite early promises, the EIT faces a few challenges for the breast imaging application. It is mainly due to its limited resolution and especially for the tumors in depth. However, unlike the other medical applications of EIT, such as brain and thorax, breast tissues are deformable. This article exploits the deformation of breast shape to enhance the EIT resolution and its depth detection. Exterior boundary of the breast can be used to create deformable EIT with multiple shapes to enhance the imaging resolution, turning a challenge to an opportunity. With deformation of the boundary shape, more independent measurements can be obtained, and hence, more information can be gained. This can increase the resolution of the reconstructed image and possible detection for smaller tumors in depth. This article demonstrates it by experimental verification in phantom test representing tumor size inclusion deep inside the breast by a few deformed shape phantoms. To evaluate the experimental results, 3-D printed phantoms are built in several different shapes. Quantitative image analysis shows that some of the deformed shapes are superior to a traditional circular cross section. Additionally, we proposed a combination of data from all shapes so that all this information can be used in one step reconstruction to achieve higher imaging accuracy.</p

Investigation of 3D electrical impedance mammography systems for breast cancer detection

Breast cancer is a major disease in women worldwide with a high rate of mortality, second only to lung cancer. Hence, there is considerable interest in developing non-invasive breast cancer detection methods with the aim of identifying breast cancer at an early stage, when it is most treatable. Electrical impedance mammography (EIM) is a relatively new medical imaging method for breast cancer detection. It is a safe, painless, non-invasive, non-ionizing imaging modality, which visualizes the internal conductivity distribution of the breast under investigation. Currently some EIM systems are in clinical trials but not commercialized, as there are still many challenges with sensitivity, spatial resolution and detectability. The research in this thesis aims to enhance and optimize EIM systems in order to address the current challenges. An enhanced image reconstruction algorithm using the duo-mesh method is developed. Both in simulations and real cases of phantoms and patients, the enhanced algorithm has proven more accurate and sensitive than the former algorithm and effective in improving vertical resolution for the EIM system with a planar electrode array. To evaluate the performance of the EIM system and the image reconstruction algorithms, an image processing based error analysis method is developed, which can provide an intuitive and accurate method to evaluate the reconstructed image and outline the shape of the object of interest. Two novel EIM systems are studied, which aim to improve the spatial resolution and the detectability of a tumour deep in the breast volume. These are: rotary planar-electrode-array EIM (RPEIM) system and combined electrode array EIM (CEIM) system. The RPEIM system permits the planar electrode array to rotate in the horizontal plane, which can dramatically increase the number of independent measurements, hence improving the spatial resolution. To support the rotation of the planner electrode array, a synchronous mesh method is developed. The CEIM system has a planar electrode array and a ring electrode array operated independently or together. It has three operational modes. This design provides enhanced detectability of a tumour deep within the tissue, as required for a large volume breast. The studies of the RPEIM system and the CEIM system are based on close-to-realistic digital breast phantoms, which comprise of skin, nipple, ducts, acini, fat and tumour. This approach makes simulations very close to a clinical trial of the technology