Table of contents

This issue of Physiological Measurement follows the successful 14th International Conference on Electrical Bioimpedance and the 11th International Conference on Biomedical Applications of Electrical Impedance Tomography. The conference was hosted at the University of Florida, Gainesville, USA. It was organized by Rosalind Sadleir from the University of Florida, with Eung Je Woo of Kyung Hee University.

The conference provided a platform for investigators in all aspects of bioimpedance and electrical impedance tomography (EIT) to converse on common areas of interest, whilst also being an opportunity for the community to broaden its outlook in the areas of clinical applications and new technologies and providing a link to researchers working on the measurement of bio-impedance, key to the development of impedance tomography and its clinical applications.

A highlight of the meeting was the presentation of the Herman P Schwan award to bioimpedance leader Professor Sverre Grimnes (University of Oslo). The student paper competition was won by Christian Tronstad, also of the University of Oslo.

The conference was privileged to host four eminent keynote speakers, headed by Professor Jakko Malmivuo (Tampere University of Technology, Tampere, Finland) who presented an address entitled 'Principle of reciprocity solves the most important problems in bioimpedance and in general in bioelectromagnetism', and Professor Bin He (University of Minnesota at Twin Cities, Minnesota, USA) who examined 'Electrical source and impedance imaging of biological tissues: opportunities and challenges'. Important clinical perspectives on applications of bioimpedance and EIT were provided by Dr Nathan W Levin (Albert Einstein College of Medicine and Renal Research Institute, New York, USA) who spoke on 'Bioimpedance applications: a nephrologist's point of view' and Dr Gerhard K Wolf (Children's Hospital Boston, Massachusetts, USA) whose presentation was 'Lung imaging with electrical impedance tomography: will it change management?'

Two events particularly appreciated by younger members of the bioimpedance and EIT communities were a pre-conference workshop on 'Bioelectricity basics' organized by Sverre Grimmes and Ørjan Martinsen, with contributions from Richard Bayford and Uwe Pliquett, and a two-day intensive course on bioelectromagnetism by Professor Malmivuo, based on the text Bioelectromagnetism by Malmivuo and Plonsey.

This issue contains papers stemming from discussions and feedback in these research areas during the conference. It was also an opportunity for new researchers to join the community and propose innovations. A total of 131 oral papers were presented at the conference, and all authors were invited to prepare new peer-reviewed papers for submission to this issue of Physiological Measurement. The manuscripts were put through a careful review process before selection. A total of 18 were accepted, covering an important range of topics.

The papers included in this issue clearly reflect the continuing interest in both bioimpedance and EIT, producing a wide range of clinical applications that were strongly represented at the conference. These include brain function, breast and thorax imaging. It is important that researchers do not neglect the challenges that clinical applications of bioimpedance and EIT present, as there are still many technical difficulties the technology needs to overcome in order to provide valuable clinical tools. However, there are promising signs that these tools are moving closer to realization, particularly for thorax imaging.

Both bioimpedance and EIT continue to provide researchers with new challenges and attract more researchers into these research areas, as evident by the number of attendees at this conference (176). The high quality of the research papers in this issue is clear evidence of the significant advances in the field. At the end of the meeting it was announced that the next joint conference will be held in Heilbad Heiligenstadt, Germany in 2013. We look forward to another successful meeting at that time.

We characterize the ability of electrical impedance tomography (EIT) to distinguish changes in internal conductivity distributions, and analyze it as a function of stimulation and measurement patterns. A distinguishability measure, z, is proposed which is related to the signal-to-noise ratio of a medium and to the probability of detection of conductivity changes in a region of interest. z is a function of the number of electrodes, the EIT stimulation and measurement protocol, the stimulation amplitude, the measurement noise, and the size and location of the contrasts. Using this measure we analyze various choices of stimulation and measurement patterns under the constraint of medical electrical safety limits (maximum current into the body). Analysis is performed for a planar placement of 16 electrodes for simulated 3D tank and chest shapes, and measurements in a saline tank. Results show that the traditional (and still most common) adjacent stimulation and measurement patterns have by far the poorest performance (by 6.9 ×). Good results are obtained for trigonometric patterns and for pair drive and measurement patterns separated by over 90°. Since the possible improvement over adjacent patterns is so large, we present this result as a call to action: adjacent patterns are harmful, and should be abandoned. We recommend using pair drive and measurement patterns separated by one electrode less than 180°. We describe an approach to modify an adjacent pattern EIT system by adjusting electrode placement.

Electrical impedance tomography (EIT) measures the conductivity distribution within an object based on the current applied and voltage measured at surface electrodes. Thus, EIT images are sensitive to electrode properties (i.e. contact impedance, electrode area and boundary shape under the electrode). While some of these electrode properties have been investigated individually, this paper investigates these properties and their interaction using finite element method simulations and the complete electrode model (CEM). The effect of conformal deformations on image reconstruction when using the CEM was of specific interest. Observed artefacts were quantified using a measure that compared an ideal image to the reconstructed image, in this case a no-noise reconstruction that isolated the electrodes' effects. For electrode contact impedance and electrode area, uniform reductions to all electrodes resulted in ringing artefacts in the reconstructed images when the CEM was used, while parameter variations that were not correlated amongst electrodes resulted in artefacts distributed throughout the image. When the boundary shape changed under the electrode, as with non-symmetric conformal deformations, using the CEM resulted in structured distortions within the reconstructed image. Mean electrode contact impedance increases, independent of inter-electrode variation, did not result in artefacts in the reconstructed image.

This paper addresses the problem of calculating the bioimpedance phase angle from measurements of impedance modulus. A complete impedance measurement was performed on altogether 20 healthy persons using a Solatron 1260/1294 system. The obtained impedance modulus (absolute impedance value) values were used to calculate the Cole parameters and from them the phase angles. In addition, the phase angles were also calculated using a Kramers–Kronig approach. A correlation analysis for all subjects at each frequency (5, 50, 100 and 200 kHz) for both methods gave R² values ranging from 0.7 to 0.96 for the Cole approach and from 0.83 to 0.96 for the Kramers–Kronig approach; thus, both methods gave good results compared with the complete measurement results. From further statistical significance testing of the absolute value of the difference between measured and calculated phase angles, it was found that the Cole equation method gave significantly better agreement for the 50 and 100 kHz frequencies. In addition, the Cole equation method gives the four Cole parameters (R₀, R_∞, τ_z and α) using measurements at frequencies up to 200 kHz while the Kramers–Kronig method used frequencies up to 500 kHz to reduce the effect of truncation on the calculated results. Both methods gave results that can be used for further bioimpedance calculations, thus improving the application potential of bioimpedance measurement results obtained using relatively inexpensive and portable measurement equipment.

Electrical impedance tomography (EIT) is a non-invasive imaging modality which has been actively studied for its industrial as well as medical applications. However, the performance of the inverse algorithms to reconstruct the conductivity images using EIT is often sub-optimal. Several factors contribute to this poor performance, including high sensitivity of EIT to the measurement noise, the rounding-off errors, the inherent ill-posed nature of the problem and the convergence to a local minimum instead of the global minimum. Moreover, the performance of many of these inverse algorithms heavily relies on the selection of initial guess as well as the accurate calculation of a gradient matrix. Considering these facts, the need for an efficient optimization algorithm to reach the correct solution cannot be overstated. This paper presents an oppositional biogeography-based optimization (OBBO) algorithm to estimate the shape, size and location of organ boundaries in a human thorax using 2D EIT. The organ boundaries are expressed as coefficients of truncated Fourier series, while the conductivities of the tissues inside the thorax region are assumed to be known a priori. The proposed method is tested with the use of a realistic chest-shaped mesh structure. The robustness of the algorithm has been verified, first through repetitive numerical simulations by adding randomly generated measurement noise to the simulated voltage data, and then with the help of an experimental setup resembling the human chest. An extensive statistical analysis of the estimated parameters using OBBO and its comparison with the traditional modified Newton–Raphson (mNR) method are presented. The results demonstrate that OBBO has significantly better estimation performance compared to mNR. Furthermore, it has been found that OBBO is robust to the initial guess of the size and location of the boundaries as well as offering a reasonable solution when the a priori knowledge of the conductivity of the organs is not very accurate.

X-ray mammography is the standard for breast cancer screening. The development of alternative imaging modalities is desirable because mammograms expose patients to ionizing radiation. Electrical impedance tomography (EIT) may be used to determine tissue conductivity, a property which is an indicator of cancer presence. EIT is also a low-cost imaging solution and does not involve ionizing radiation. In breast EIT, impedance measurements are made using electrodes placed on the surface of the patient's breast. The complex conductivity of the volume of the breast is estimated by a reconstruction algorithm. EIT reconstruction is a severely ill-posed inverse problem. As a result, noisy instrumentation and incorrect modelling of the electrodes and domain shape produce significant image artefacts. In this paper, we propose a method that has the potential to reduce these errors by accurately modelling the patient breast shape. A 3D hand-held optical scanner is used to acquire the breast geometry and electrode positions. We develop methods for processing the data from the scanner and producing volume meshes accurately matching the breast surface and electrode locations, which can be used for image reconstruction. We demonstrate this method for a plaster breast phantom and a human subject. Using this approach will allow patient-specific finite-element meshes to be generated which has the potential to improve the clinical value of EIT for breast cancer diagnosis.

We have developed a robust EEG-based current pattern which shows promise for the detection of intraventricular hemorrhage (IVH) in neonates. Our reconstructions to date are based on a layered spherical head model. In this study, the current pattern was used to gather data from three realistic-shaped neonatal head models and a physical phantom based on one of these models. We found that a sensitivity matrix calculated from a spherical model gave us satisfactory reconstructions in terms of both image quality and quantification. Incorporating correct geometry information into the forward model improved image quality. However, it did not improve quantification accuracy. The results indicate that using a spherical matrix may be a more practical choice for monitoring IVH volumes in neonates for whom patient-specific models are not available.

Electrical impedance tomography (EIT) solves an inverse problem to estimate the conductivity distribution within a body from electrical simulation and measurements at the body surface, where the inverse problem is based on a solution of Laplace's equation in the body. Most commonly, a finite element model (FEM) is used, largely because of its ability to describe irregular body shapes. In this paper, we show that simulated variations in the positions of internal nodes within a FEM can result in serious image artefacts in the reconstructed images. Such variations occur when designing FEM meshes to conform to conductivity targets, but the effects may also be seen in other applications of absolute and difference EIT. We explore the hypothesis that these artefacts result from changes in the projection of the anisotropic conductivity tensor onto the FEM system matrix, which introduces anisotropic components into the simulated voltages, which cannot be reconstructed onto an isotropic image, and appear as artefacts. The magnitude of the anisotropic effect is analysed for a small regular FEM, and shown to be proportional to the relative node movement as a fraction of element size. In order to address this problem, we show that it is possible to incorporate a FEM node movement component into the formulation of the inverse problem. These results suggest that it is important to consider artefacts due to FEM mesh geometry in EIT image reconstruction.

We report the development of a new multi-frequency electrical impedance tomography (EIT) system called the KHU Mark2. It is descended from the KHU Mark1 in terms of technical details such as digital waveform generation, Howland current source with multiple generalized impedance converters and digital phase-sensitive demodulators. New features include flexible electrode configurations to accommodate application-specific requirements, multiple independent current sources and voltmeters for fully parallel operations, improved data acquisition speeds for faster frame rates and compact mechanical design. Given an electrode configuration, we can design an analog backplane in such a way that both current injections and voltage measurements can be done without using any switch. The KHU Mark2 is based on an impedance measurement module (IMM) comprising a current source and a voltmeter. Using multiple IMMs, we can construct a multi-channel system with 16, 32 or 64 channels, for example. Adopting a pipeline structure, it has the maximum data acquisition speed of 100 scans s⁻¹ with the potential to detect fast physiological changes during respiration and cardiac activity. Measuring both in-phase and quadrature components of trans-impedances at multiple frequencies simultaneously, the KHU Mark2 is apt at spectroscopic EIT imaging. In this paper, we describe its design, construction, calibration and performance evaluation. It has about 84 dB signal-to-noise ratio and 0.5% reciprocity error. Time-difference images of an admittivity phantom are presented showing spectroscopic admittivity images. Future application studies using the KHU Mark2 are briefly discussed.

An electrical impedance tomography (EIT) system images internal conductivity from surface electrical stimulation and measurement. Such systems necessarily comprise multiple design choices from cables and hardware design to calibration and image reconstruction. In order to compare EIT systems and study the consequences of changes in system performance, this paper describes a systematic approach to evaluate the performance of the EIT systems. The system to be tested is connected to a saline phantom in which calibrated contrasting test objects are systematically positioned using a position controller. A set of evaluation parameters are proposed which characterize (i) data and image noise, (ii) data accuracy, (iii) detectability of single contrasts and distinguishability of multiple contrasts, and (iv) accuracy of reconstructed image (amplitude, resolution, position and ringing). Using this approach, we evaluate three different EIT systems and illustrate the use of these tools to evaluate and compare performance. In order to facilitate the use of this approach, all details of the phantom, test objects and position controller design are made publicly available including the source code of the evaluation and reporting software.

Previous studies demonstrate that it is possible to evaluate a heart graft rejection condition using a bioimpedance technique by means of an intracavitary catheter. We propose to use a less invasive technique consisting in the use of a transoesophageal catheter and two standard ECG electrodes on the thorax. The aim of this work is to evaluate, using the finite element method, several parameters affecting the transoesophageal impedance measurement, including sensitivity to electrical conductivity and permittivity of different organs in the thorax, changes in magnitude and phase due to a lesion producing a scar, a global ischaemia of the heart, pleural effusion in the lungs, fat thickness increase, displacement of the catheter inside the oesophagus and movement of one electrode on the thorax surface. From these results, we deduce the best estimator for cardiac rejection detection and obtain the tools to identify eventual cases of false positives due to other factors. To achieve these objectives we have created a thoracic model and we have simulated different situations at the frequencies of 13, 30, 100, 300 and 1000 kHz. Our simulation demonstrates that the phase, at 100 and 300 kHz, would be a better estimator than the magnitude to evaluate a heart rejection condition.

Pulmonary oxygen (O₂) uptake during apnoea results in a fall in lung volume. Given that electrical impedance tomography (EIT) provides reliable data on regional lung volume changes we hypothesized that EIT could be used to measure regional O₂ uptake. A total of 12 lung healthy supine patients were studied. EIT measurements were performed during volume-controlled mechanical ventilation followed by apnoea with the endotracheal tube clamped at end-expiration. Lung function parameters were assessed by spirometry. A device for breath-by-breath monitoring metabolic gas exchange was used to measure global O₂ uptake. Relative impedance changes during ventilation and apnoea were related to the corresponding tidal volumes. Regional O₂ uptake was analysed as absolute values and as a ratio to regional ventilation in two regions of interest (ventral and dorsal). The global O₂ uptake measured by EIT was 208 ± 79 ml min⁻¹ corresponding to the values obtained by metabolic gas exchange (259 ± 73 ml min⁻¹; Spearman correlation coefficient: 0.81, p = 0.02). Regional O₂ uptake was significantly higher in the ventral lung region, while the regional O₂ uptake/ventilation ratio showed no significant difference between the regions. In conclusion, our pilot study indicates that EIT holds substantial potential to detect global and regional pulmonary O₂ uptake concordant with a linear lung volume decrease during apnoea.

Prescription of an appropriate dialysis target weight (dry weight) requires accurate evaluation of the degree of hydration. The aim of this study was to investigate whether a state of normal hydration (DW_cBIS) as defined by calf bioimpedance spectroscopy (cBIS) and conventional whole body bioimpedance spectroscopy (wBIS) could be characterized in hemodialysis (HD) patients and normal subjects (NS). wBIS and cBIS were performed in 62 NS (33 m/29 f) and 30 HD patients (16 m/14 f) pre- and post-dialysis treatments to measure extracellular resistance and fluid volume (ECV) by the whole body and calf bioimpedance methods. Normalized calf resistivity (ρ_N,5) was defined as resistivity at 5 kHz divided by the body mass index. The ratio of wECV to total body water (wECV/TBW) was calculated. Measurements were made at baseline (BL) and at DW_cBIS following the progressive reduction of post-HD weight over successive dialysis treatments until the curve of calf extracellular resistance is flattened (stabilization) and the ρ_N,5 was in the range of NS. Blood pressures were measured pre- and post-HD treatment. ρ_N,5 in males and females differed significantly in NS. In patients, ρ_N,5 notably increased with progressive decrease in body weight, and systolic blood pressure significantly decreased pre- and post-HD between BL and DW_cBIS respectively. Although wECV/TBW decreased between BL and DW_cBIS, the percentage of change in wECV/TBW was significantly less than that in ρ_N,5 (−5.21 ± 3.2% versus 28 ± 27%, p < 0.001). This establishes the use of ρ_N,5 as a new comparator allowing a clinician to incrementally monitor removal of extracellular fluid from patients over the course of dialysis treatments. The conventional whole body technique using wECV/TBW was less sensitive than the use of ρ_N,5 to measure differences in body hydration between BL and DW_cBIS.

Current methods for identifying ventilated lung regions utilizing electrical impedance tomography images rely on dividing the image into arbitrary regions of interest (ROI), manually delineating ROI, or forming ROI with pixels whose signal properties surpass an arbitrary threshold. In this paper, we propose a novel application of a data-driven classification method to identify ventilated lung ROI based on forming k clusters from pixels with correlated signals. A standard first-order model for lung mechanics is then applied to determine which ROI correspond to ventilated lung tissue. We applied the method in an experimental study of 16 mechanically ventilated swine in the supine position, which underwent changes in positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (F_IO₂). In each stage of the experimental protocol, the method performed best with k = 4 and consistently identified 3 lung tissue ROI and 1 boundary tissue ROI in 15 of the 16 subjects. When testing for changes from baseline in lung position, tidal volume, and respiratory system compliance, we found that PEEP displaced the ventilated lung region dorsally by 2 cm, decreased tidal volume by 1.3%, and increased the respiratory system compliance time constant by 0.3 s. F_IO₂ decreased tidal volume by 0.7%. All effects were tested at p < 0.05 with n = 16. These findings suggest that the proposed ROI detection method is robust and sensitive to ventilation dynamics in the experimental setting.

Magnetic induction tomography (MIT) has been proposed for the detection of cerebral oedema and haemorrhagic stroke. Achieving the required phase measurement precision for these applications is however a major technical challenge. A critical component within an MIT system is the detector amplifier and for this role an ultra-phase-stable, low noise instrumentation amplifier has been developed. The design of the amplifier is described and (i) the results of simulations and measurements of the amplifiers phase stability versus temperature and (ii) measurements of the phase noise and drift performance of the amplifier within a single-channel magnetic induction spectroscopy system are provided and discussed. For a 10 MHz signal the amplifier, with a gain of 21, displayed an average change in the measured phase of its output of just −0.1 ± 0.6 m° °C^–1 as the ambient temperature was varied between 35 and 50 °C, demonstrating a level of phase stability approaching that required for potential biomedical applications such as the detection of cerebral haemorrhage.

Fast impedance measurements are often performed in time domain utilizing broad bandwidth excitation signals. Other than in frequency domain measurements harmonic distortion cannot be compensated which requires careful design of the analog front end. In order to minimize the influence of electrode polarization and noise, especially in low-frequency measurements, current injection shows several advantages compared to voltage application. Here, we show an active front end based on a voltage-controlled current source for a wide range of impedances. Using proper feedback, the majority of the parasitic capacitances are compensated. The bandwidth ranges from dc to 20 MHz for impedance magnitude below 5 kΩ. The output is a symmetric signal without dc-offset which is accomplished by combination of a current conveyor and a voltage inverter. An independent feedback loop compensates the offset arising from asymmetries within the circuitry. We focused especially on the stability of the current source for usage with small metal electrodes in aqueous solutions. At the monitor side two identical, high input impedance difference amplifiers convert the net current through the object and the voltage dropping across into a 50 Ω symmetric output. The entire circuitry is optimized for step response making it suitable for fast time domain measurements.

An impedance spectrum of dynamic systems is time dependent. Fast impedance changes take place, for example, in high throughput microfluidic devices and in operating cardiovascular systems. Measurements must be as short as possible to avoid significant impedance changes during the spectrum analysis, and as long as possible for enlarging the excitation energy and obtaining a better signal-to-noise ratio (SNR). The authors propose to use specific short chirp pulses for excitation. Thanks to the specific properties of the chirp function, it is possible to meet the needs for a spectrum bandwidth, measurement time and SNR so that the most accurate impedance spectrogram can be obtained. The chirp wave excitation can include thousands of cycles when the impedance changes slowly, but in the case of very high speed changes it can be shorter than a single cycle, preserving the same excitation bandwidth. For example, a 100 kHz bandwidth can be covered by the chirp pulse with durations from 10 µs to 1 s; only its excitation energy differs also 10⁵ times. After discussing theoretical short chirp properties in detail, the authors show how to generate short chirps in the microsecond range with a bandwidth up to a few MHz by using digital synthesis architectures developed inside a low-cost standard field programmable gate array.

Multicycle harmonic (Fourier) analysis of bioimpedance was employed to simultaneously assess circulation and neural activity in visceral (rat urinary bladder) and somatic (human finger) organs. The informative value of the first cardiac harmonic of the bladder impedance as an index of bladder circulation is demonstrated. The individual reactions of normal and obstructive bladders in response to infusion cystometry were recorded. The potency of multicycle harmonic analysis of bioimpedance to assess sympathetic and parasympathetic neural control in urinary bladder is discussed. In the human finger, bioimpedance harmonic analysis revealed three periodic components at the rate of the heart beat, respiration and Mayer wave (0.1 Hz), which were observed under normal conditions and during blood flow arrest in the hand. The revealed spectrum peaks were explained by the changes in systemic blood pressure and in regional vascular tone resulting from neural vasomotor control. During normal respiration and circulation, two side cardiac peaks were revealed in a bioimpedance amplitude spectrum, whose amplitude reflected the depth of amplitude respiratory modulation of the cardiac output. During normal breathing, the peaks corresponding to the second and third cardiac harmonics were split, reflecting frequency respiratory modulation of the heart rate. Multicycle harmonic analysis of bioimpedance is a novel potent tool to examine the interaction between the respiratory and cardiovascular system and to simultaneously assess regional circulation and neural influences in visceral and somatic organs.

Living cultured cells react to external influences, such as pharmaceutical agents, in an intricate manner due to their complex internal signal processing. Impedance sensing of cells on microelectrodes is a favored label-free technology to indicate cellular events, usually ascribed to morphologic alteration or changes in cellular adhesion, which is usually found in stand-alone systems that do not incorporate life support or additional sensor systems. However, only in symbiosis with metabolic activity sensing and picture documentation may a complete insight into cellular vitality be provided. This complement was created within the framework of an automated high-content screening system previously developed by our group, monitoring 24 cell culture chambers in parallel. The objective of this paper is the development of miniaturized electronics for impedance measurements and its system integration as a modular unit. In addition, it is shown how sensor electrodes were optimized by impedance matching such that spectroscopy and raw data analysis become feasible for every culture well. Undesired mechanical stress on cultured cells may arise from the medium and agent support system of the autonomous screening apparatus. This paper demonstrates how this hazard is treated with the simulation of microfluidics and impedance measurements. Physiological data are subsequently derived from the exemplary tumor cell line MCF-7 both during treatment with the agent doxorubicin and through the impact of natural killer cells. This correlates the information content of complex impedance spectra with cellular respiration as well as data from microscopy.