Tetrapolar Impedance Measurements Research Articles

Sensitivity study of a locally developed six electrode focused impedance method.

The Focused Impedance Method (FIM) is a new technique of electrical bioimpedance measurements in the human body. The idea originated in Bangladesh and provides an opportunity for localized measurement of bioimpedance down to reasonable depths from the body surface using skin surface electrodes. This has potential applications for physiological studies of targeted organs in the body and in detecting or diagnosing diseases and disorders. FIM is based on the age-old Tetra-Polar Impedance Measurement (TPIM) but provides a few significant improvements. Technology must be developed indigenously to obtain long-term benefits, particularly in Low and Medium Income countries (LMIC). This paper presents an experimental sensitivity study of the six-electrode version of the Focused Impedance method (FIM-6) with the circuit and phantom indigenously designed in Nepal. The work involved sensitivity studies of both FIM-6 and TPIM with the necessary circuit blocks developed through experimental validation. The sensitivity studies were performed on a simple 2D phantom with different electrode arrangements for FIM-6 and linear TPIM. A cylindrical object was placed at different positions for this study. The FIM-6 gave a high sensitivity in the central part, which remained almost constant within a small region that may be termed as the focused region. On the other hand, TPIM results fell off sharply away from the central point, making it unsuitable for practical measurements on target organs. Besides, there were areas with large negative sensitivities in TPIM, which were much smaller in FIM. The results obtained through this work clearly show the improvement offered by FIM over TPIM.

Probing Deep Lung Regions using a New 6-electrode Tetrapolar Impedance Method.

Probing deep regions of the lung using electrical impedance is very important considering the need for a low cost and simple technique, particularly for the low and medium income countries. Because of complexity and cost, Electrical Impedance Tomography is not suitable for this envisaged application. The simple Tetrapolar Impedance Measurement (TPIM) technique employing four electrodes is the age old technique for bioelectrical measurements. However, it has its limitations in respect of organ localisation and depth sensitivity using skin surface electrodes. Recently, a new 6-electrode TPIM with two current electrodes but two pairs of appropriately connected potential electrodes positioned on the front and back of the thorax, proposed by one of the authors, came with a promise. However, this work gave a qualitative proposal based on concepts of physics and lacked a quantitative evaluation. In order to evaluate the method quantitatively, the present work employed finite element method based COMSOL Multiphysics software and carried out simulation studies using this new 6-electrode TPIM and compared the results with those from 4-electrode TPIM, with electrodes applied either on the front or at the back of the thorax for the latter. Initially, it carried out a sensitivity distribution study using a simple rectangular volume conductor which showed that the 6-electrode TPIM gives better depth sensitivity throughout the lung region. Next it used a near life like thorax model developed by another of the authors earlier. Using this model, extensive studies were carried out to quantify the overall sensitivity over a target lung region, the contribution of the target lung to the total measured impedance, and several other parameters. Through these studies, the 6-electrode TPIM was established on a stronger footing for probing deep regions of the lungs.

Improving Deep Sensitivity of Four-Electrode Focused Impedance Method In Lungs by Varying Electrode Geometries

Bio-Electrical impedance is of special interest in the detection and diagnosis of lung problems, particularly in the low and medium income countries. An age old simple technique employing four electrodes is known as ‘Tetra Polar Impedance Measurement (TPIM)’ but it cannot localize a particular zone of interest region. A new technique named as ‘Focused Impedance Method (FIM)’ was innovated by a Dhaka University group which gives high sensitivity in a localized zone of interest. Previously FIM was used from one side of the thorax which gave a rather limited information from the lungs, from shallow depths only. In order to get information from deeper regions of the lungs a new configuration of electrodes for FIM was proposed by the same group at Dhaka University which placed two electrodes at the front and two electrodes at the back of the thorax in a horizontal plane. It is expected that the degree of depth sensitivity would depend on electrode separation on both the sides. The electrode width may also have an effect. In order to study these quantitatively, COMSOL Multiphysics software was used to simulate the measurements in a rounded rectangular volume to represent a typical thorax, which was filled with isotonic saline. Electrode separations of 5cm, 10cm, 15cm and 20cm were studied while electrode widths studied were 0.15cm, 1cm and 3cm. The work supported the proposed new configuration of electrodes for FIM in that this method gives enhanced sensitivity throughout the depths of a lung and that for a thorax with a cross section of 33cm26cm, an electrode separation between 10cm and 15cm would give optimum results. For electrode width, the ones studied did not give any significant difference, however, the smallest (0.15cm) one appeared to give slightly better results.
 Bangladesh Journal of Medical Physics Vol.15 No.1 2022 P 43-54

A Multi-Frequency Focused Impedance Measurement System Based on Analogue Synchronous Peak Detection

Monitoring of anatomical structures and physiological processes by electrical impedance has attracted scientists as it is noninvasive, nonionizing and the instrumentation is relatively simple. Focused Impedance Method (FIM) is attractive in this context, as it has enhanced sensitivity at the central region directly beneath the electrode configuration minimizing contribution from neighboring regions. FIM essentially adds or averages two concentric and orthogonal combinations of conventional Tetrapolar Impedance Measurements (TPIM) and has three versions with 4, 6, and 8 electrodes. This paper describes the design and testing of a multi-frequency FIM (MFFIM) system capable of measuring all three versions of FIM at 8 frequencies in the range 10 kHz—1 MHz. A microcontroller based multi-frequency signal generator and a balanced Howland current source with high output impedance (476 kΩ at 10 kHz and 58.3 kΩ at 1 MHz) were implemented for driving currents into biological tissues with an error <1%. The measurements were carried out at each frequency sequentially. The peak values of the amplified voltage signals were measured using a novel analogue synchronous peak detection technique from which the transfer impedances were obtained. The developed system was tested using TPIM measurements on a passive RC Cole network placed between two RC networks, the latter representing skin-electrode contact impedances. Overall accuracy of the measurement was very good (error <4% at all frequencies except 1 MHz, with error 6%) and the resolution was 0.1 Ω. The designed MFFIM system had a sampling rate of >45 frames per second which was deemed adequate for noninvasive real-time impedance measurements on biological tissues.

Proposal of a Lab Bench for the Unobtrusive Monitoring of the Bladder Fullness with Bioimpedance Measurements.

(1) Background: millions of people, from children to the elderly, suffer from bladder dysfunctions all over the world. Monitoring bladder fullness with appropriate miniaturized textile devices can improve, significantly, their daily life quality, or even cure them. Amongst the existing bladder sensing technologies, bioimpedance spectroscopy seems to be the most appropriate one to be integrated into textiles. (2) Methods: to assess the feasibility of monitoring the bladder fullness with textile-based bioimpedance spectroscopy; an innovative lab-bench has been designed and fabricated. As a step towards obtaining a more realistic pelvic phantom, ex vivo pig’s bladder and skin were used. The electrical properties of the fabricated pelvic phantom have been compared to those of two individuals with tetrapolar impedance measurements. The measurements’ reproducibility on the lab bench has been evaluated and discussed. Moreover, its suitability for the continuous monitoring of the bladder filling has been investigated. (3) Results: although the pelvic phantom failed in reproducing the frequency-dependent electrical properties of human tissues, it was found to be suitable at 5 kHz to record bladder volume change. The resistance variations recorded are proportional to the conductivity of the liquid filling the bladder. A 350 mL filling with artificial urine corresponds to a decrease in resistance of 7.2%, which was found to be in the same range as in humans. (4) Conclusions: based on that resistance variation; the instantaneous bladder fullness can be extrapolated. The presented lab-bench will be used to evaluate the ability of textiles electrodes to unobtrusively monitor the bladder volume.

Probing for Stomach using the Focused Impedance Method (FIM).

For probing deep organs of the body using electrical impedance, the conventional method is to use Electrical Impedance Tomography (EIT). However, this would be a sophisticated machine and will be very expensive when a full 3D EIT is developed in the future. Furthermore, for most low income countries such expensive devices may not deliver the benefits to a large number of people. Therefore, this paper suggests the use of simpler techniques like Tetrapolar Impedance Measurement (TPIM) or Focused Impedance Method (FIM) in probing deeper organs. Following a method suggested earlier by one of the authors, this paper studies the possibility of using TPIM and FIM for the stomach. Using a simplified model of the human trunk with an embedded stomach, a finite element simulation package, COMSOL, was used to obtain transfer impedance values and percentage contribution of the stomach region in the total impedance. For this work, judicious placement of electrodes through qualitative visualizations based on point sensitivity equations and equipotential concepts were made, which showed that reasonable contribution of the stomach region is possible through the use of TPIM and FIM. The contributions were a little over 20% which is of similar order of the cross-sectional area percentage of the stomach with respect to that of the trunk. For the case where the conductivity of the stomach region was assumed about 4 times higher, the contributions increased to about 38%. Through further studies this proposed methods may contribute greatly in the study of deeper organs of the body.

A new six-electrode electrical impedance technique for probing deep organs in the human body.

Electrical impedance measurements of biological tissue have many potential applications and tetrapolar impedance measurement (TPIM) with four electrodes is traditionally used which eliminates high skin contact impedance. A linear array of four electrodes for TPIM on the horizontal plane of a cylindrical volume conductor of diameter D, where the length of the array is πD/2 with potential electrodes near the centre of the array, will give a high sensitivity near the surface which reduces rapidly with depth. A recently proposed six-electrode variation of TPIM uses an additional pair of potential electrodes on the opposite side of the volume conductor in the same horizontal plane around the circumference, with the expectation that the sensitivity of the deeper regions will thereby be enhanced. The present work carries out a finite element simulation (using COMSOL) and an experimental phantom study (saline phantom) to quantitatively evaluate the improvement obtained by this new method. The new configuration doubled the sensitivity at the central region, which was reasonably uniform over a wider zone, gradually increasing towards the potential electrodes on both sides. This would be useful for a range of biological studies of deep body organs such as lungs, stomach, and bladder. where the respective external body shapes may be approximated by an oval cylinder and where electrical impedance techniques have shown promise.

Effect of the electrode surface on the tetrapolar impedance measurements of Hela Cells in suspension

Electrical impedance spectroscopy (EIS) measurements with four electrodes is widely used in the study of electrical properties of cells in suspension. Under less than ideal conditions, this set up enables the removal the surface polarization effects. However, in the case of HeLa cells in suspension, we noted that the electrical impedance spectra reproducibility is affected by the impurities and ionic species adsorbed on the electrode surface. We studied the influence of the electrode’s surface conditions on the EIS measurements of HeLa cells in suspension. EIS spectra were obtained before and after submitting the electrodes to a cleaning process. Chronopotentiometry and open circuit potential (OCP) measurements were carried out to verify the electrode’s surface conditions. The main effect of cleaning the electrodes was to decrease the standard deviation of the EIS data (On average, 3.42? to 0.70? for PBS and 17.22? to 0.31? for PBS with HeLa cells). OCP measurements evidenced surface differences between the cleaned and uncleaned electrodes. In addition, the chronopotentiometric curve obtained for the gold electrode/PBS system showed the adsorption of chloride and phosphate ions and other species existing in PBS on the electrode surface at 0.28 V and 0.53 V. Results suggest that the adsorbed species on the electrode surface led to an electrostatic build-up, which has a non-passive behavior.

Addition of internal electrodes is beneficial for focused bioimpedance measurements in the lung

Objective: Bioimpedance measurements such as bioimpedance spectroscopy (BIS) or electrical impedance tomography (EIT) are used in many biomedical applications. While BIS measures and analyzes the impedance in a frequency range at constant electrode positions, EIT aims to reconstruct images of the conductivity distribution from multiple measurements at different electrode positions. Our aim is to add spatial information to tetrapolar BIS measurements by using electrode positions that focus measurements on desired regions of interest. In this paper, we aim to investigate, whether internal electrodes that can be integrated into breathing or gastroesophageal tubes, can improve the local sensitivity of bioimpedance spectroscopy measurements. Approach: We present the results of a simulation study, in which we investigated more than 4 M different electrode configurations on their ability to monitor specific regions of interest (ROI) in the lung. Based on the sensitivity, which describes the impact of a conductivity change on the measured impedance, we define three main criteria which we use to evaluate our simulation results: the selectivity , which describes the impact of a conductivity change inside the region of interest compared to a conductivity change outside the ROI; the homogeneity , which describes the distribution of the sensitivity inside the ROI; and the absolute impedance contribution ratio , which describes the contribution of the ROI to the measured impedance. Main results: Depending on the region of interest, electrode configurations using internal electrodes are between 9.8 % and 90 % better with respect to these criteria than configurations using external electrodes only. Significance: The combination of internal and external electrodes improves the focusing ability of tetrapolar impedance measurements on specific lung regions, which may be especially beneficial for lung monitoring in intensive care.

Improved Understanding of the Sensitivity of Linear Tetrapolar Impedance Measurement (TPIM) and 8-Electrode Focused Impedance Method (FIM) in a Volume Conductor

Tetrapolar Impedance Measurement (TPIM) is a 4-electrode impedance measurement system appropriate for a volume conductor in which current is driven through a pair of electrodes while potential developed across another pair of electrodes is measured to provide a value of transfer impedance. The 8-electrode Focused Impedance Method (FIM-8) consists of two concentric and orthogonal linear TPIM systems with their transfer impedances added for the purpose of localizing the central zone. Detailed 3D sensitivity studies are necessary for proper application of the techniques in specific biomedical applications and most reported work present point sensitivity distributions. The present work mainly focuses on planar average sensitivity in planes parallel to the electrode plane and its variation with depth due to different combinations of electrode separations – both for current drive pair and the potential measuring pair. This was obtained through finite element simulation using COMSOL Multiphysics software for a 40x40x40cm3 volume. The results give useful information that can be used to design electrode configurations and measurement modalities for various applications.Bangladesh Journal of Medical Physics Vol.8 No.1 2015 22-31

Sensitivity Analysis of the Tetrapolar Electrical Impedance Measurement Systems Using COMSOL Multiphysics for the non-uniform and Inhomogeneous Medium

One of the major problems with Electrical Impedance Tomography (EIT) is the lack of spatial sensitivity within the measured volume. In this paper, sensitivity distribution of the tetrapolar impedance measurement system was visualized considering a cylindrical phantom consisting of homogeneous and inhomogeneous medium. Previously, sensitivity distribution was analysed analytically only for the homogeneous medium considering simple geometries and the distribution was found to be complex1,2. However, for the inhomogeneous volume conductors sensitivity analysis needs to be done using finite element method (FEM). In this paper, the results of sensitivity analysis based on finite element method using COMSOL Multiphysics simulation software are presented. A cylindrical non-uniform, inhomogeneous phantom, which mimics the human upper arm, was chosen to do the experiments by varying different parameters of interest. A successful method for controlling the region of interest was found where the sensitivity was maximum. Refining the finite element mesh size and introducing multifrequency input current (up to 1 MHz) this simulation method can be further improved.Dhaka Univ. J. Sci. 64(1): 7-13, 2016 (January)

Tidal volume monitoring by a set of tetrapolar impedance measurements selected from the 16-electrodes arrangement used in electrical impedance tomography (EIT) technique. Calibration equations in a group of healthy males

Abstract Previously, our research group obtained a set of calibration equations for being used by an electrical impedance tomograph (EIT). All equations transform the impedance changes into a measurable volume signal in a group of healthy males. The performance of EIT, using these equations, was acceptable for respiration monitoring. The EIT impedance changes were obtained from a set of 16-electrodes placed around the thoracic box at level of the sixth intercostal space. Each cycle of impedance measurements is ordered in a matrix (IEITM). Each IEITM's element depicts a configuration of 4-electrodes. Now, our main challenge is to replace the EIT's 16-electrodes by a 4-electrodes configuration. We analyzed the impedance changes obtained from each element and the volume determinations obtained by a pneumotachometer (gold standard) in order to determine the optimal 4-electrodes configuration. For each selected configuration a set of 20 calibration equations were obtained. The best results were obtained by using two 4-electrodes configurations. Both consisting in two adjacent electrodes for current injection and two electrodes for voltage detection. The mean R 2 of the 20 equations determined by the 16-electrodes information, and for the best two 4-electrode configurations were 0.943 ± 0.010, 0.848 ± 0.062 and 0.690 ± 0.122, respectively. The error (%) of volume determinations obtained by the use of 16-electrodes, and by the use of the two best 4-electrode configuration with regarding to the real volume obtained by pneumotachometer were of 15 ± 6%, 16 ± 4% and 43 ± 41%, respectively. The volume differences between the one obtained by the use of 16-electrodes and that for the best 4 electrode configuration were not significant. We conclude that although the determinations of impedance obtained by the best 4-electrode configuration has a lower sensitivity than those obtained by the 16-electrodes, it is possible to measure the respiratory pattern in healthy males.

Improvement of the in vitro recordings in cortical slices by using customized flexible neuroprobes

Event Abstract Back to Event Improvement of the in vitro recordings in cortical slices by using customized flexible neuroprobes Xavi Illa1, 2*, Beatriz Rebollo3, Gemma Gabriel1, 2, Maria V. Sanchez-Vives3, 4 and Rosa Villa1, 2 1 CIBER-BBN, Spain 2 IMB-CNM, CSIC, Spain 3 IDIBAPS, Spain 4 ICREA, Spain We have explored the feasibility of improving the quality of multiple recordings from spontaneously oscillating cortical slices. With that purpose we have taken advantage of the advances performed in the development of flexible neuproprobes, either fabricated on polyimide, SU-8, PDMS or parylene (Hassler et al. 2011). With these materials the contact between the electrodes and the tissue is enhanced with respect to the neuroprobes fabricated on rigid substrates, such as silicon or pyrex. However, we had to find a compromise between the necessity to achieve a good contact between the electrode and the slice and the need to allow the flow of oxygenated solution to the slice to maintain its healthy state when using flexible neuroprobes. To overcome this limitation, we have designed, fabricated and characterized a 16-electrode flexible neuroprobe that allocates an array of holes in its sensing area. This neuroprobe has been developed using SU-8 negative photoresist as a substrate material in the clean room facilities of the IMB-CNM. In particular, the neuroprobes have been fabricated following the process described in a previous article from the authors (Guimerà et al. 2013); using silicon wafers with an aluminum sacrificial layer as a support for the fabrication process. Then, the neuroprobes were released from the wafer by an anodic dissolution of the aluminum layer (Metz et al. 2005). In order to validate the usability of the fabricated device, the neuroprobes were used to record spontaneous slow oscillations to study the wave propagation along the cortical networks while manipulating them by means of pharmacological drugs or electric fields. We conclude that the perforated devices provide substantial improvement in the adherence of the electrodes to the tissue, on the mechanical stability of the recordings, and in the healthiness of the slices. Acknowledgements This work has been supported by the Spanish Ministry of Economy and Competitiveness, BFU2011-27094 (MVSV) and SAF2012-40227- C02-02 (RV), the European Regional Development Fund (RV), EU project CORTICONIC (Contract number 600806, MVSV) and the Graphene Flagship Initiative of the European Commision via the NEUROGRAPHENE project (Contract 604391, MVSV and RV). References Hassler, C., Boretius, T., Stieglitz, T. (2011). Polymers for neural implants. J. Polym. Sci. Pol. Phys. 49, 18-33 Guimerà, A., Illa, X., Traver, E., Plata-Cordero, M., Yeste, J., Herrero, C., Lagunas, L., Maldonado, M. J., Villa, R. (2013). Flexible probe for in vivo quantification of corneal epithelium permeability through non-invasive tetrapolar impedance measurements. Biomed. Microdevices 15, 849-858 Metz, S., Bertsch, A., Renaud, P. (2005). Partial release and detachment of microfabricated metal and polymer structures by anodic metal dissolution. J. Microelectromech. Syst. 14, 383-391 Keywords: SU-8, Neuroprobe, cortical network, microfabrication, spontaneous activity Conference: B·DEBATE | A Dialogue with the Cerebral Cortex: Cortical Function and Interfacing (Workshop), Barcelona, Spain, 29 Apr - 30 Apr, 2015. Presentation Type: Poster Presentation Topic: SESSION 3: Interfacing with the Cerebral Cortex: New Technologies Citation: Illa X, Rebollo B, Gabriel G, Sanchez-Vives MV and Villa R (2015). Improvement of the in vitro recordings in cortical slices by using customized flexible neuroprobes. Front. Syst. Neurosci. Conference Abstract: B·DEBATE | A Dialogue with the Cerebral Cortex: Cortical Function and Interfacing (Workshop). doi: 10.3389/conf.fnsys.2015.06.00001 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Apr 2015; Published Online: 06 May 2015. * Correspondence: Dr. Xavi Illa, CIBER-BBN, Barcelona, Spain, xavier.illa@imb-cnm.csic.es Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Xavi Illa Beatriz Rebollo Gemma Gabriel Maria V Sanchez-Vives Rosa Villa Google Xavi Illa Beatriz Rebollo Gemma Gabriel Maria V Sanchez-Vives Rosa Villa Google Scholar Xavi Illa Beatriz Rebollo Gemma Gabriel Maria V Sanchez-Vives Rosa Villa PubMed Xavi Illa Beatriz Rebollo Gemma Gabriel Maria V Sanchez-Vives Rosa Villa Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Classification of breast tumour using electrical impedance and machine learning techniques

When a breast lump is detected through palpation, mammography or ultrasonography, the final test for characterization of the tumour, whether it is malignant or benign, is biopsy. This is invasive and carries hazards associated with any surgical procedures. The present work was undertaken to study the feasibility for such characterization using non-invasive electrical impedance measurements and machine learning techniques. Because of changes in cell morphology of malignant and benign tumours, changes are expected in impedance at a fixed frequency, and versus frequency of measurement. Tetrapolar impedance measurement (TPIM) using four electrodes at the corners of a square region of sides 4 cm was used for zone localization. Data of impedance in two orthogonal directions, measured at 5 and 200 kHz from 19 subjects, and their respective slopes with frequency were subjected to machine learning procedures through the use of feature plots. These patients had single or multiple tumours of various types in one or both breasts, and four of them had malignant tumours, as diagnosed by core biopsy. Although size and depth of the tumours are expected to affect the measurements, this preliminary work ignored these effects. Selecting 12 features from the above measurements, feature plots were drawn for the 19 patients, which displayed considerable overlap between malignant and benign cases. However, based on observed qualitative trend of the measured values, when all the feature values were divided by respective ages, the two types of tumours separated out reasonably well. Using K-NN classification method the results obtained are, positive prediction value: 60%, negative prediction value: 93%, sensitivity: 75%, specificity: 87% and efficacy: 84%, which are very good for such a test on a small sample size. Study on a larger sample is expected to give confidence in this technique, and further improvement of the technique may have the ability to replace biopsy.

New trends in quantitative assessment of the corneal barrier function.

The cornea is a very particular tissue due to its transparency and its barrier function as it has to resist against the daily insults of the external environment. In addition, maintenance of this barrier function is of crucial importance to ensure a correct corneal homeostasis. Here, the corneal epithelial permeability has been assessed in vivo by means of non-invasive tetrapolar impedance measurements, taking advantage of the huge impact of the ion fluxes in the passive electrical properties of living tissues. This has been possible by using a flexible sensor based in SU-8 photoresist. In this work, a further analysis focused on the validation of the presented sensor is performed by monitoring the healing process of corneas that were previously wounded. The obtained impedance measurements have been compared with the damaged area observed in corneal fluorescein staining images. The successful results confirm the feasibility of this novel method, as it represents a more sensitive in vivo and non-invasive test to assess low alterations of the epithelial permeability. Then, it could be used as an excellent complement to the fluorescein staining image evaluation.

Adverse effects of near current-electrode placement in non-invasive bio-impedance measurements

A major problem confronting application of impedance techniques to studies of disease is the extraction of intrinsic properties of the tissue from the measured impedances, which unavoidably involve geometric factors as well. Amongst the foremost are the sizes and locations of the measuring electrode arrays, and this paper addresses one of these, the location of current injecting electrodes. Tetrapolar impedance measurements on a 17.5 cm segment of the thigh gave R and X values three to four times larger when the current injecting electrodes were placed 2.5 cm from the sensing electrodes than when very distant placement was used. The frequency dependences of R and X were affected as well, though the X versus R plots still showed virtually perfect depressed-center semicircles, as in the Cole model. R(f) and X(f) for the set of contiguous 2.5 cm wide sub-segments show that these behaviors can be explained by a combination of the transverse orientation of current flow lines near the injecting electrodes and the anisotropy of the resistivity associated with the bundled fiber structure of muscle tissue. The measured impedance was found to be a separable function of geometric and intrinsic tissue variables, but far more complicated than is implicit in the usual cylindrical models. The results also suggest that many full and segmental body composition studies in the literature may be prone to substantial errors due to too close placement of the current injecting electrodes.

The possible use of combined electrical impedance and ultrasound velocity measurements for the non-invasive measurement of temperature during mild hyperthermia

This paper explores the possibility of using combined measurements of electrical impedance and changes in ultrasound time of flight for determining deep body temperature during mild hyperthermia. Simultaneous electrical impedance spectra (1 kHz–1024 kHz) and ultrasound time-of-flight measurements were made on layered sheep liver and fat tissue samples as the temperature was increased from 30–50 °C. The change in propagation velocity for 100% fat and 100% liver samples was found to vary linearly with temperature and the temperature coefficient of the time-of-flight was shown to vary linearly with the % fat in the sample (0.009% °C−1%−1). Tetrapolar impedance measurements normalized to 8 kHz were shown to have a small sensitivity to temperature for both liver (0.001% °C−1 ≤ 45 °C) and fat (0.002% °C−1 ≤ 512 kHz) and the best linear correlation between the normalized impedance and the % fat in the sample was found at 256 kHz (gradient 0.026%−1, r2 = 0.65). A bootstrap analysis on 15 layered tissue samples evaluated using the normalized impedance at 256 kHz to determine the % fat in the sample and the temperature coefficient of the time of flight to determine the temperature. The results showed differences (including some large differences) between the predicted and measured temperatures and an error evaluation identified the possible origins of these.

Flexible probe for in vivo quantification of corneal epithelium permeability through non-invasive tetrapolar impedance measurements

Studies concerning the functional status of the corneal epithelium are of special interest due to its key role in preventing ocular surface disease and corneal infections. In particular, quantitative measurements of the epithelium permeability translayer electrical resistance (TER) have been proven as a sensitive in vitro test for evaluation of the corneal barrier function. In a recent work from the authors (Guimera et al. Biosens. Bioelectron. 31:55-61, 2012), a novel method to non-invasively assess the corneal epithelial permeability by using tetrapolar impedance measurements, based on the same TER theoretical principles, was presented and validated using a rigid sensing device. In this work, the usability of this method has been dramatically improved by using SU-8 photoresist as a substrate material. The flexibility of this novel sensing device makes no need to apply pressure on the cornea to ensure the electrical contact between the electrodes and the corneal surface. The feasibility of this flexible sensor has been evaluated in vivo by increasing the permeability of rabbit corneal epithelium. For that, different concentrations of benzalkonium chloride (BAC) solution were instilled on different rabbit corneas. The obtained results have been compared with measurements of the permeability to sodium fluorescein of different excised corneas, a well-known method used to evaluate the corneal barrier function, to demonstrate the feasibility of this novel flexible sensor for quantifying the corneal epithelium permeability in vivo in a non-invasive way.

In vivo assessment of corneal barrier function through non-invasive impedance measurements using a flexible probe

The cornea is a transparent structure composed of three layers: the epithelium, the stroma and the endothelium. To maintain its ransparency the stroma remains in a constant state of dehydration. Consequently, any ion flow disorder through the covering layers can compromise the barrier function and, therefore the corneal homeostasis. Since ionic permeability has a fundamental impact on the passive electrical properties of living tissues, in this work it is proposed and demonstrated a diagnosis method based on tetrapolar impedance measurements performed by electrodes placed on the corneal surface. The contribution of each cornea layer to the total measured impedance has been analysed over a frequency range. Following the obtained guidelines, a flexible probe with integrated electrodes has been developed and manufactured using SU-8 photoresin. The feasibility of the proposed method has been evaluated in vivo by monitoring corneal epithelium wound healing. Obtained impedance measurements have been compared with measurements of permeability to sodium fluorescein from different excised corneas. Successful results demonstrate the feasibility of this novel flexible sensor and its capability to quantify corneal permeability in vivo in a noninvasive way.

A non-invasive method for an in vivo assessment of corneal epithelium permeability through tetrapolar impedance measurements

The permeability of the cornea epithelial layer has an important role in optimal function of the cornea. To assess this property quantitatively, methods must be based on the passive electrical properties of living tissues, as they can take advantage of the fundamental role that ionic permeability plays in such properties. For such techniques, measurement of the translayer electrical resistance (TER) has been consistently used to examine the ion transport mechanisms in the corneal epithelial cells; however, this technique has been only possible in vitro. To enhance the applications of this method, in this work we present a novel sensor to perform non-invasive in vivo TER measurements. Herein, the epithelial permeability was assessed using non-invasive tetrapolar impedance measurements that were performed with four electrodes placed on the corneal surface. The geometry of these electrodes was previously optimized to maximize the sensitivity of the corneal epithelium. To evaluate the feasibility of this sensor, the permeability of a rabbit corneal epithelium was monitored by applying a solution of benzalkonium chloride (0.05% BAC). The results validate the capability of the sensor to evaluate the cornea epithelial permeability in vivo.