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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.

The thesis discusses various electrode models and finite element analysis methods for Electrical Impedance Tomography (EIT) systems. EIT is a technique for determining the distribution of the conductivity or admittivity in a volume by injecting electrical currents into the volume and measuring the corresponding potentials on the surface of the volume. Various electrode models were investigated for operating EIT systems at higher frequencies in the beta-dispersion band. Research has shown that EIT is potentially capable to distinguish malignant and benign tumours in this frequency band. My study concludes that instrumental effects of the electrodes and full Maxwell effects of EIT systems are the major issues, and they have to be addressed when the operating frequency increases. In the thesis, I proposed 1) an Instrumental Electrode Model (IEM) for the quasi-static EIT formula, based on the analysis of the hardware structures attached to electrodes; 2) a Complete Electrode Model based on Impedance Boundary Conditions (CEM-IBC) that introduces the contact impedances into the full Maxwell EIT formula; 3) a Transmission line Port Model (TPM) for electrode pairs with the instrumental effects, the contact impedance, and the full Maxwell effects considered for EIT systems. Circuit analysis, Partial Differential Equations (PDE) analysis, numerical analysis and finite element methods were used to develop the models. The results obtained by the proposed models are compared with widely used Commercial PDE solvers. This thesis addresses the two major problems (instrumental effects of the electrodes and full Maxwell effects of EIT systems) with the proposed advanced electrode models. Numerical experiments show that the proposed models are more accurate in the high frequency range of EIT systems. The proposed electrode models can be also applicable to inverse problems, and the results show promising. Simple hardware circuits for verifying the results experimentally have been also designed.

The research concentrates on the design, development and calibration of a high performance Electrical Impedance Mammography (EIM) system for early detection of breast cancer at the macro and micro scale (at an early stage applicable for different breast sizes and shapes). The enhancement of the Electrical Impedance Tomography (EIT) system focuses on developing electrical and electronic instrumentations and improving the current source topologies to make them operate at multiple frequencies for the purpose of measuring permittivity and conductivity of different breast tissues. The calibration, assessment systems have employed current calibration in the EIT to evaluate the impedance distribution. This facilitates the acquisition of accurate impedance images to enable images of the internal structure of the breast to be constructed. A constraint on EIT systems is that the current injection system suffers from the effects of stray capacitance having a major impact on the hardware subsystem as the EIT is an ill-posed inverse problem which depends on the noise level in EIT measured data and regularization parameter in the reconstruction algorithm. This research aims are to prevent this problem by using a capacitance cancellation method based on a General Impedance Converter (GIC) implemented by operation of a second generation of current conveyor called OCCII-GIC and calibration methods to facilitate operation in the high frequency range. An EIT system based on a planar 85-electrode channel and using a Microcontroller unit (MCU) for addressing control between 85 electrodes and implementing calibration methods has been constructed. In EIT systems, assessment, validation of the performance and calibration of systematic errors in the electrical field generated inside of the interrogated volume is important. Evaluation of the EIT system will be assessed using a realistic electronic phantom (E-phantom). This enables the evaluation of the different conductivity values of the tissue, which has been created and evaluated based on the RSC circuit model for the different electrical conductivities and electrical impedivities in breast tissue.

PARENTE, Marcelo Valente. Estudo eletroquímico da adsorção de moléculas organosulfuradas sobre superfície de ouro. 2006. 96 f. Tese (Doutorado em Química Inorgânica) – Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2006. / Submitted by irlana araujo (irlanaaraujo@gmail.com) on 2011-12-29T13:52:25Z No. of bitstreams: 1 2006_tes_Mar Araujo.pdf: 1449434 bytes, checksum: 32dcd49372c754f4a613c3064f4fa5e0 (MD5) / Approved for entry into archive by Aline Nascimento(vieiraaline@yahoo.com.br) on 2012-02-14T14:26:06Z (GMT) No. of bitstreams: 1 2006_tes_Mar Araujo.pdf: 1449434 bytes, checksum: 32dcd49372c754f4a613c3064f4fa5e0 (MD5) / Made available in DSpace on 2012-02-14T14:26:06Z (GMT). No. of bitstreams: 1 2006_tes_Mar Araujo.pdf: 1449434 bytes, checksum: 32dcd49372c754f4a613c3064f4fa5e0 (MD5) Previous issue date: 2006-08-04 / Modified gold surface with organosulfur species, 1,4-dithiane (1,4-dt) and 4- mercaptopyridine (pyS), was studied in this work. The study was carried out using the following electrochemical techniques: linear polarization with rotate disk electrode, cyclic voltammetry, differential pulse voltammetry, electrohydrodynamic impedance and electrochemical impedance spectroscopy. Other techniques also gave support, such as, atomic force microscopy (AFM), Scanning tunneling microscopy (STM), RAMAN spectroscopy and quartz crystal microbalance (QCM). For the modified gold surface with the 1,4-dt, it was observed the decrease of the redox-active [Fe(CN)6]3- species with the increase of the immersion time of the gold electrode in the modifier solution. These results suggest that the fractional coverage increases with the modification time. The electrohydrodynamic impedance results together with the MFA and MST results suggest that this surface is partially blocked presenting defects on the formed film. The RAMAN spectra suggest that those defects can be resulting of the adsorption of the different configuration of the modifier molecules (1,4-dt) on the surface ("trans" and "gauche"). The electrochemical results about the modified gold surfaces with the molecule pyS indicate an increase of the electron transfer process with the increase of the immersion time, which suggests the loss of the covering power on the modified gold surface with this species. The AFM results agree the previous results demonstrating that this surface presents larger amount of defects for longer modification times. The frequency curves variation (ΔF) versus the immersion time indicate a mass increase on the modified gold surface with the species 1,4-dt and a process desorption for the species pyS confirming the results obtained previously. / Superfície de ouro modificada com as espécies 1,4-ditiano (1,4-dt) e 4- mercaptopiridina (pyS), foram estudadas neste trabalho. Para a realização desse estudo foram utilizadas as seguintes técnicas eletroquímicas: polarização linear com eletrodo de disco rotatório, voltametria cíclica, voltametria de pulso diferencial, impedância eletro-hidrodinâmica e espectroscopia de impedância eletroquímica. Outras técnicas também deram suporte, tais como, microscopia de força atômica (MFA), microscopia de superfície por tunelamento (MST), espectroscopia RAMAN e microbalança de quartzo (MBQ). Para as superfícies modificadas com a molécula 1,4-dt, foi observado a diminuição do processo redox [Fe(CN)6]3-/4- com o aumento do tempo de imersão do eletrodo de ouro na solução modificadora. Estes resultados sugerem que taxa de recobrimento da superfície de ouro, com esta espécie, aumenta com o tempo de modificação. Os resultados de impedância eletro-hidrodinâmica juntamente com as micrografias MFA e MST revelam que esta superfície está parcialmente bloqueada apresentando defeitos sobre o filme formado. Os resultados de espectroscopia RAMAN sugerem que esses defeitos podem ser resultantes da adsorção das conformações diferenciadas na forma de “cadeira” e “barco” da molécula 1,4 dt. Por outro lado, os resultados eletroquímicos com as superfícies modificadas com a espécie pyS indicam um aumento do processo de transferência de carga com o aumento do tempo de imersão do eletrodo de ouro na solução modificadora. Este resultado sugere a perda do poder de cobertura para a superfície de ouro modificada com esta espécie. Os resultados de MFA reforçam os resultados anteriores para esta espécie demonstrando que esta superfície apresenta maiores quantidade de defeitos para tempos mais longos de modificação. As curvas de variação de freqüência (ΔF) versus tempo de modificação indicam um aumento de massa na superfície de ouro modificada com a espécie 1,4-dt, enquanto que para a espécie pyS observa-se um processo de desorção, confirmando qualitativamente os resultados obtidos anteriores para estas duas moléculas.

The Electrical Impedance Mammography (EIM) device is an imaging system developed at the University of Sussex for the detection of breast lesions in vivo using quadrature detection of impedance. The work describes a novel technique to integrate Ultrasound-guided Focused Ultrasound Surgery (USgFUS) with the existing EIM system. The benefits that such a system could provide include the possibility of non-invasive detection, diagnosis and treatment of breast cancer all within a single device and involving no radiation. Furthermore the timescales involved would allow the process to be considered an outpatient procedure such that a patient can be diagnosed and treated on the same day using the same device. Various geometries of transducer were investigated for physical compatibility as well as the ability to target the entire specified volume, based on the dimensions of the existing system. Simulations were performed using a custom written code based on Huygen's principle, allowing minimum surface area and power requirements to be determined and feasibility of designs to be evaluated. The use of phase differences in the excitation signals applied to individual elements was also investigated, thus the effect of steering the simulated focus could be observed, an important factor to consider when attempting to incorporate a transducer into a device with restricted dimensions. Resulting simulated pressure fields were used to obtain acoustic intensity fields, which could then be used as inputs in the Pennes Bio-Heat Transfer Equation (BHTE) allowing temperature distributions to be observed. Preliminary studies proved the feasibility of using the suggested transducer design in conjunction with the existing EIM system. Pressure fields and heating patterns were all within acceptable limits, confirming the ability of the device to effectively ablate cancerous tissue. Additionally the capability to steer the resultant focal point was validated, and a thermal dose model was implemented allowing different heating patterns to be quantitatively compared.

Electrical Impedance Tomography is a non-invasive, non-ionizing, non-destructive and painless imaging technology that can distinguish between cancerous and non-cancerous cells by reproducing tomographic images of the electrical impedance distribution within the body. The primary scope of this thesis is the study of hardware modules required for an EIT system. The key component in any EIT system is the excitation system. Impedance measurement can be performed by applying either a current or voltage through emitting electrodes and then measuring the resulting voltages or current on receiving electrodes. In this research, both types of excitation systems are investigated and developed for the Sussex EIM system. Firstly, a current source (CS) excitation system is investigated and developed. The performance of the excitation system degrades due to the unwanted capacitance within the system. Hence two CS circuits: Enhance Howland Source (EHS) and EHS combined with a General impedance convertor (GIC: to minimise the unwanted capacitance) are evaluated. Another technique (guard-amplifier) has also been investigated and developed to minimise the effect of stray capacitance. The accuracy of both types of CS circuits are evaluated in terms of its output impedance along with other performance parameters for different loading conditions and the results are compared to show their performance. Both CS circuits were affected by the loading voltage problem. A bootstrapping technique is investigated and integrated with both CS circuits to overcome the loading voltage problem. The research shows that both CS circuits were unable to achieve a high frequency bandwidth (i.e. ≥10MHz) and were limited to 2-3MHz. Alternatively, a discrete components current source was also investigated and developed to achieve a high frequency bandwidth and other desirable performance parameters. The research also introduces a microcontroller module to control the multiplexing involved for different CS circuit configurations via serial port interface software running on a PC. For breast cancer diagnosis, the interesting characteristics of breast tissues mostly lie above 1MHz, therefore a wideband excitation source covering high frequencies (i.e. ≥1-10MHz) is required. Hence, a second type of the excitation system is investigated. A constant voltage source (VS) circuit was developed for a wide frequency bandwidth with low output impedance. The research investigated three VS architectures and based on their initial bandwidth comparison, a differential VS system was developed to provide a wide frequency bandwidth (≥10MHz). The research presents the performance of the developed VS excitation system for different loading configurations reporting acceptable performance parameters. A voltage measurement system is also developed in this research work. Two different differential amplifier circuits were investigated and developed to measure precise differential voltage at a high frequency. The research reports a performance comparison of possible types of excitation systems. Results are compared to establish their relationship to performance parameters: frequency bandwidth, output impedance, SNR and phase difference over a wide bandwidth (i.e. up to 10MHz). The objective of this study is to investigate which design is the most appropriate for constructing a wideband excitation system for the Sussex EIM system or any other EIT based biomedical application with wide a bandwidth requirement.

Worldwide, breast cancer accounts for 22% of all cancer incidences in women, causing 458,503 deaths per annum [WHO 2008]. The most common screening method is X-ray mammography, an ionising method, which has many technical and age group limitations and has come under scrutiny for accuracy and safety on many occasions. Electrical Impedence Mammography (EIM) is a novel, non-invasive, non-ionising imaging modality based on bioimpedence. Initial test results show it as very promising; however the image resolution is quite low. Ultrasound imaging is widely used for high-resolution medical imaging and clinical diagnostics. Ultrasound is non-invasive and is effective in imaging soft body tissue, including subcutaneous structures and organs, but fails to distinguish tissue type. Merging the information of the above modalities and integrating them in an automated device offers a safe, non-invasive, fast, higher accuracy, breast cancer detection method for all age groups. To explore the proposed system, the work was divided into cumulative integrative stages: investigation of the technical challenges of a real world breast scanner device for each modality and the combination of both, including engineering, repeatability, safety and ergonomics, to adhere to medical device standards; data acquisition systems design, signal processing and calibration; image geometry correction; 3D image reconstruction; volumetric merger and visualisation; validation with dual modality scans on phantom and in-vivo; DICOM image porting. These modalities were successfully combined in a unified automated breast scanner that can accommodate and scan 95% of women (breast volume up to 1200cc) in a safe and comfortable way. Data acquisition and scan time achieved is five minutes per breast. The image results achieved from this research complement each other by integrating the boundary information of Ultrasound with the impedence data and tissue discrimination of EIM, therefore potentially providing a more complete and accurate cancer diagnostic method. The images were successfully ported into the DICOM radiology imaging standard therefore becoing platform independent. This work concluded with over twenty academic publications and two filed patents on the technology of a breast scanner and on the methodology of its imaging.

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.

The thesis aims to develop an ISFET chip compatible miniaturized planar reference. Such planar reference electrode will be constructed by: silica / silica oxide / titanium / palladium / silver / silver chloride / saturated KCl agar / silica nitride / silica. For the size of the reference electrode is only 10mm (length), 5mm (width) and 1mm (height), which is diminished of hundred-fold to the traditional reference electrode. In addition to develop the fabrication techniques of the electrodes, this thesis will be devoted to systematic measuring and analyzing their stability, AC impedence, cyclic voltammery and electrochemical noise characteristics. The results show that the stability is inside 1mV, offset voltage is about -9 mV and the resistance of AC impedence is 400