Batch Processing of Electrical Bioimpedance Spectroscopy Measurements. Implementation and Validation

Projecte final de carrera realitzat en col.laboració amb University of Borås School of EngineeringNowadays, Electrical Bioimpedance (EBI) measurements have become a common practice as they are useful for different clinical applications for non-invasive monitoring. In recent years new applications of EBI measurements based in spectral analysis have risen and been validated. Due to this fact, the use of spectral analysis on Electrical Bioimpedance measurements is going to open the door for new indicators for health assessment. One of the goals of this thesis is to provide functions for the development of a Software tool for Electrical Bioimpedance Spectroscopy analysis, the other is to design and implement functions to perform a batch analysis of EBI measurements of different subjects for comparison. Once these objectives have been implemented, spectral analysis and validation of characterization features will be checked easily, accelerating the process of test and analysis of experimental data analysis

Development of real-time cellular impedance analysis system

The cell impedance analysis technique is a label-free, non-invasive method, which simplifies sample preparation and allows applications requiring unmodified cell retrieval. However, traditional impedance measurement methods suffer from various problems (speed, bandwidth, accuracy) for extracting the cellular impedance information. This thesis proposes an improved system for extracting precise cellular impedance in real-time, with a wide bandwidth and satisfactory accuracy. The system hardware consists of five main parts: a microelectrode array (MEA), a stimulation circuit, a sensing circuit, a multi-function card and a computer. The development of system hardware is explored. Accordingly, a novel bioimpedance measurement method coined digital auto balancing bridge method, which is improved from the traditional analogue auto balancing bridge circuitry, is realized for real-time cellular impedance measurement. Two different digital bridge balancing algorithms are proposed and realized, which are based on least mean squares (LMS) algorithm and fast block LMS (FBLMS) algorithm for single- and multi-frequency measurements respectively. Details on their implementation in FPGA are discussed. The test results prove that the LMS-based algorithm is suitable for accelerating the measurement speed in single-frequency situation, whilst the FBLMS-based algorithm has advantages in stable convergence in multi-frequency applications. A novel algorithm, called the All Phase Fast Fourier Transform (APFFT), is applied for post-processing of bioimpedance measurement results. Compared with the classical FFT algorithm, the APFFT significantly reduces spectral leakage caused by truncation error. Compared to the traditional FFT and Digital Quadrature Demodulation (DQD) methods, the APFFT shows excellent performance for extracting accurate phase and amplitude in the frequency spectrum. Additionally, testing and evaluation of the realized system has been performed. The results show that our system achieved a satisfactory accuracy within a wide bandwidth, a fast measurement speed and a good repeatability. Furthermore, our system is compared with a commercial impedance analyzer (Agilent 4294A) in biological experiments. The results reveal that our system achieved a comparable accuracy to the commercial instrument in the biological experiments. Finally, conclusions are given and the future work is proposed

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

An investigation into multi-spectral excitation power sources for Electrical Impedance Tomography

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

Impedance spectroscopy for in vitro toxicology

The impedance of biological material changes with frequency, a phenomenon that has been discovered more than 100 years ago. It is due to the fact that the cell membrane acts as a capacitor which filters out currents at low frequency and lets them pass at high frequency. This fundamental knowledge about biological dielectrics has incompletely been exploited to detect and distinguish toxicity effects on cell cultures, although impedance measurements have been used for long in this field. In this thesis, it was found that low frequency impedance signals are linked to initial stress responses of cells within cell populations when exposed to a toxin whereas high frequency measurements inform about major cell damage as is indicated by intracellular conductivity changes. In addition, when cells gain resistance to a toxin, they experience a higher cell stiffness which is expressed by an increased low frequency impedance. The study of impedance changes as a function of frequency and drug concentrations lead to the creation of an impedimetric concentration-response map which distinguishes cell responses within four concentration ranges without the use of any label. Although being inherently non-specific, this measurement method was shown to report on distinct toxicity effects, an important prerequisite when studying drug action on cancer cells where stimulating and lethal effects need to be distinguished rigorously. This thesis further encompasses the subject of three-dimensional impedance measurements, i.e. the screening of the entire depth of a three-dimensional tissue culture. Given the success of impedance measurements on cell monolayers, one would expect this development to continue with 3D cultures since the complex structure of in vivo tissues is mimicked more closely and, above all, since rapid and inexpensive techniques which are able to probe thick tissue samples are currently inexistent. Nevertheless, few studies have been carried out in this field. Here, the requirements of three-dimensional impedance sensors are discussed and challenged by the fabrication of a corresponding device, involving the development of so-called gel electrodes through a novel 2-step-soft-lithography process. Their specific design allows for the decrease of leak currents, a common problem when performing three-dimensional impedance measurements. The simultaneous measurement of multiple samples in parallel is an an essential condition when performing high throughput drug toxicity screening. Electrode switch systems are necessary which ultimately lead to setup complexity and signal noises. In this thesis, a method is introduced, enabling the simultaneous implementation of impedance measurements of multiple tissue samples with one electrode pair only. This is simply achieved by exploiting the frequency domain and finally contributed to reducing setup complexity