Bioimpedance real-time charazterization of neointimal tissue inside stents

It is hereby presented a new approach to monitor restenosis in arteries fitted with a stent during an angioplasty. The growth of neointimal tissue is followed up by measuring its bioimpedance with Electrical Impedance Spectroscopy (EIS). Besides, a mathematical model is derived to analytically describe the neointima’s histological composition from its bioimpedance. The model is validated by finite-element analysis (FEA) with COMSOL Multiphysics®. Satisfactory correlation between the analytical model and the FEA simulation is achieved for most of the characterization range, detecting some deviations introduced by the thin "double layer" that separates the neointima and the blood. It is shown how to apply conformal transformations to obtain bioimpedance models for stack-layered tissues over coplanar electrodes. Particularly, this is applied to characterize the neointima in real-time. This technique is either suitable as a main mechanism of restenosis follow-up or it can be combined with proposed blood-pressure-measuring intelligent stents to auto-calibrate the sensibility loss caused by the adherence of the tissue on the micro-electro-mechanical sensors (MEMS).Ministerio de Economía, Industria y Competitividad (Spain): projects TEC2013-46242-C3-1-PMinisterio de Economía, Industria y Competitividad (Spain): projects TEC2013-46242-C3-2-

Real-time electrical bioimpedance characterization of neointimal tissue for stent applications

To follow up the restenosis in arteries stented during an angioplasty is an important current clinical problem. A new approach to monitor the growth of neointimal tissue inside the stent is proposed on the basis of electrical impedance spectroscopy (EIS) sensors and the oscillation-based test (OBT) circuit technique. A mathematical model was developed to analytically describe the histological composition of the neointima, employing its conductivity and permittivity data. The bioimpedance model was validated against a finite element analysis (FEA) using COMSOL Multiphysics software. A satisfactory correlation between the analytical model and FEA simulation was achieved in most cases, detecting some deviations introduced by the thin “double layer” that separates the neointima and the blood. It is hereby shown how to apply conformal transformations to obtain bioimpedance electrical models for stack-layered tissues over coplanar electrodes. Particularly, this can be applied to characterize the neointima in real-time. This technique is either suitable as a main mechanism for restenosis follow-up or it can be combined with proposed intelligent stents for blood pressure measurements to auto-calibrate the sensibility loss caused by the adherence of the tissue on the micro-electro-mechanical sensors (MEMSs).This work was carried out in collaboration with the Cardiology Department of the UHMV Hospital, Santander (Spain) and was funded by the Spanish Government’s “Ministerio de Economía, Industria y Competitividad” under the joint projects TEC2013-46242-C3-1-P and TEC2013-46242-C3, co-financed with FEDER

Smart Bioimpedance Spectroscopy Device for Body Composition Estimation

The purpose of this work is to describe a first approach to a smart bioimpedance spectroscopy device for its application to the estimation of body composition. The proposed device is capable of carrying out bioimpedance measurements in multiple configurable frequencies, processing the data to obtain the modulus and the bioimpedance phase in each of the frequencies, and transmitting the processed information wirelessly. Another novelty of this work is a new algorithm for the identification of Cole model parameters, which is the basis of body composition estimation through bioimpedance spectroscopy analysis. Against other proposals, the main advantages of the proposed method are its robustness against parasitic effects by employing an extended version of Cole model with phase delay and three dispersions, its simplicity and low computational load. The results obtained in a validation study with respiratory patients show the accuracy and feasibility of the proposed technology for bioimpedance measurements. The precision and validity of the algorithm was also proven in a validation study with peritoneal dialysis patients. The proposed method was the most accurate compared with other existing algorithms. Moreover, in those cases affected by parasitic effects the proposed algorithm provided better approximations to the bioimpedance values than a reference device.Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) PI15/00306Junta de Andalucía PIN-0394-2017Unión Europea "FRAIL

Limitations and challenges of EIT-based monitoring of stroke volume and pulmonary artery pressure.

Electrical impedance tomography (EIT) shows potential for radiation-free and noninvasive hemodynamic monitoring. However, many factors degrade the accuracy and repeatability of these measurements. Our goal is to estimate the impact of this variability on the EIT-based monitoring of two important central hemodynamic parameters: stroke volume (SV) and pulmonary artery pressure (PAP). We performed simulations on a 4D ([Formula: see text]) bioimpedance model of a human volunteer to study the influence of four potential confounding factors (electrode belt displacement, electrode detachment, changes in hematocrit and lung air volume) on the performance of EIT-based SV and PAP estimation. Results were used to estimate how these factors affect the EIT measures of either absolute values or relative changes (i.e. trending). Our findings reveal that the absolute measurement of SV via EIT is very sensitive to electrode belt displacements and lung conductivity changes. Nonetheless, the trending ability of SV EIT might be a promising alternative. The timing-based measurement of PAP is more robust to lung conductivity changes but sensitive to longitudinal belt displacements at severe hypertensive levels and to rotational displacements (independent of the PAP level). We identify and quantify the challenges of EIT-based SV and PAP monitoring. Absolute SV via EIT is challenging, but trending is feasible, while both the absolute and trending of PAP via EIT are mostly impaired by belt displacements

An Empirical-Mathematical Approach for Calibration and Fitting Cell-Electrode Electrical Models in Bioimpedance Tests

This paper proposes a new yet efficient method allowing a significant improvement in the on-line analysis of biological cell growing and evolution. The procedure is based on an empirical-mathematical approach for calibration and fitting of any cell-electrode electrical model. It is valid and can be extrapolated for any type of cellular line used in electrical cell-substrate impedance spectroscopy (ECIS) tests. Parameters of the bioimpedance model, acquired from ECIS experiments, vary for each cell line, which makes obtaining results difficult and—to some extent-renders them inaccurate. We propose a fitting method based on the cell line initial characterization,and carry out subsequent experiments with the same line to approach the percentage of well filling and the cell density (or cell number in the well). To perform our calibration technique, the so-called oscillation-based test (OBT) approach is employed for each cell density. Calibration results are validated by performing other experiments with different concentrations on the same cell line with the same measurement technique. Accordingly, a bioimpedance electrical model of each cell line is determined, which is valid for any further experiment and leading to a more precise electrical model of the electrode-cell system. Furthermore, the model parameters calculated can be also used by any other measurement techniques. Promising experimental outcomes for three different cell-lines have been achieved, supporting the usefulness of this technique

Impacto da gordura abdominal e resistência à insulina na hipertensão arterial em mulheres não-obesas

OBJECTIVE: To evaluate the impact of abdominal fat and insulin resistance on arterial hypertension of non-obese women. METHODS:Thirty-five non-obese women (NO), age 35-68 years were studied, and divided into two groups according to the presence of hypertension (BP > 140 x 90 mmHg) ( HT = hypertensive; NT = normotensive). Leptin measurement and oral glucose tolerance test (OGTT) to assess insulin were performed in these patients. A CT-scan was used to evaluate visceral (VF) and subcutaneous abdominal fat (SCF). The Central fat distribution index (CDI) was proposed to evaluate the impact of subcutaneous abdominal fat on central fat distribution in hypertensive patients. RESULTS: When compared to NT-NO (n = 17) group, HT-NO (n = 18) showed higher blood pressure levels (systolic and diastolic), greater VF area (84.40 ± 55.70 versus 37.50 ± 23.00 cm²; p = 0.036), greater SCF area (174.30 ± 83.00 versus 79.80 ± 27.40 cm²; p = 0.030), higher HOMAr index (1.59 ± 0.72 versus 0.93 ± 0.48 mmol.mU/L²; p = 0.006), higher CDI index (12.67 ± 7.04 versus 6.19 ± 2.57 cm²/kg) and higher leptin level (19.1 ± 9.6 versus 7.4 ± 3.5 ng/mL; p = 0.028). CONCLUSIONS: Arterial hypertension in non-obese women is associated with insulin resistance, central fat distribution and higher leptin levels.OBJETIVO: Avaliar o impacto da gordura abdominal e resistência à insulina na hipertensão arterial em mulheres não-obesas. MÉTODOS: Foram estudadas 35 mulheres não obesas (NO), com idade entre 35 e 68 anos, separadas em dois grupos de acordo com a presença de hipertensão arterial (PA > 140 x 90 mmHg) (HT = hipertenso; NT = normotenso). A leptina foi dosada e um OGTT realizado. Um corte tomográfico foi usado para avaliar a gordura visceral (VF) e subcutânea abdominal (SCF). O índice de distribuição central de gordura (CDI) foi proposto para avaliar o impacto da gordura subcutânea abdominal na distribuição central de gordura em pacientes hipertensas. RESULTADOS: Quando comparado ao grupo NT-NO (n = 17), o grupo HT-NO (n = 18) mostrou maiores níveis de pressão arterial (sistólica e diastólica), maior área de gordura visceral (84.40 ± 55.70 versus 37.50 ± 23.00 cm²; p = 0.036), maior área de gordura subcutânea abdominal (174.30 ± 83.00 versus 79.80 ± 27.40 cm²; p = 0.030), maior HOMAr (1.59 ± 0.72 versus 0.93 ± 0.48 mmol.mU/L²; p = 0.006), maior índice CDI (12.67 ± 7.04 versus 6.19 ± 2.57 cm²/kg) e maior nível de leptina (19.1 ± 9.6 versus 7.4 ± 3.5 ng/mL; p = 0.028). CONCLUSÕES: A hipertensão arterial em mulheres não obesas está associada à resistência à insulina, distribuição central de gordura e altos níveis de leptina.Universidade Federal de São Paulo (UNIFESP) Departamento de EndocrinologiaUNIFESP, Depto. de EndocrinologiaSciEL

Noninvasive Stroke Volume Monitoring by Electrical Impedance Tomography

In clinical practice it is of vital importance to track the health of a patient's cardiovascular system via the continuous measurement of hemodynamic parameters. Cardiac output (CO) and the related stroke volume (SV) are two such parameters of central interest as they are closely linked with oxygen delivery and the health of the heart. Many techniques exist to measure CO and SV, ranging from highly invasive to noninvasive ones. However, none of the noninvasive approaches are reliable enough in clinical settings. To overcome this limitation, we investigated the feasibility and practical applicability of noninvasively measuring SV via electrical impedance tomography (EIT), a safe and low-cost medical imaging modality. In a first step, the unclear origins of cardiosynchronous EIT signals were investigated in silico on a 4D bioimpedance model of the human thorax. Our simulations revealed that the EIT heart signal is dominated by ventricular activity, giving hope for a heart amplitude-based SV estimation. We further showed via simulations that this approach seems feasible in controlled scenarios but also suffers from some limitations. That is, EIT-based SV estimation is impaired by electrode belt displacements and by changes in lung conductivity (e.g. by respiration or liquid redistribution). We concluded that the absolute measurement of SV by EIT is challenging, but trending - that is following relative changes - of SV is more promising. In a second step, we investigated the practical applicability of this approach in three experimental studies. First, EIT was applied on 16 mechanically ventilated patients in the intensive care unit (ICU) receiving a fluid challenge to improve their hemodynamic situation. We showed that the resulting relative changes in SV could be tracked using the EIT lung amplitude, while this was not possible via the heart amplitude. The second study, performed on patients in the operating room (OR), had to be prematurely terminated due to too low variations in SV and technical challenges of EIT in the OR. Finally, the third experimental study aimed at testing an improved measurement setup that we designed after having identified potential limitations of available clinical EIT systems. This setup was tested in an experimental protocol on 10 healthy volunteers undergoing bicycle exercises. Despite the use of subject-specific 3D EIT, neither the heart nor the lung amplitudes could be used to assess SV via EIT. Changes in electrode contact and posture seem to be the main factors impairing the assessment of SV. In summary, based on in silico and in vivo investigations, we revealed various challenges related to EIT-based SV estimation. While our simulations showed that trending of SV via the EIT heart amplitude should be possible, this could not be confirmed in any of the experimental studies. However, in the ICU, where sufficiently controlled EIT measurements were possible, the EIT lung amplitude showed potential to trend changes in SV. We concluded that EIT amplitude-based SV estimation can easily be impaired by various factors such as electrode contact or small changes in posture. Therefore, this approach might be limited to controlled environments with the least possible changes in ventilation and posture. Future research should scrutinize the lung amplitude-based approach in dedicated simulations and clinical trials

Non-invasive hemodynamic monitoring by electrical impedance tomography

The monitoring of central hemodynamic parameters such as cardiac output (CO) and pulmonary artery pressure (PAP) is of paramount clinical importance to assess the health status of the cardiovascular system. However, their measurement requires the insertion of a pulmonary artery catheter, a highly invasive procedure associated with non-negligible morbidity and mortality rates. In this thesis, we investigated the clinical potential of electrical impedance tomography (EIT) - a radiation-free medical imaging technique - as a non-invasive alternative for the measurement of CO and PAP. In a first phase, we investigated the potential of EIT for the measurement of CO. This measurement is implicitly based on the hypothesis that the EIT heart signal (the ventricular component of the EIT signals) is induced by ventricular blood volume changes. This hypothesis has never been formally investigated, and the exact origins of the EIT heart signal remain subject to interpretation. Therefore, using a model, we investigated the genesis of this signal by identifying its various sources and their respective contributions. The results revealed that the EIT heart signal is dominated by cardioballistic effects (heart motion). However, although of prominently cardioballistic origin, the amplitude of the signal has shown to be strongly correlated to stroke volume (r = 0.996, p < 0.001; error of 0.57 +/- 2.19 mL). We explained these observations by the quasi-incompressibility of myocardial tissue and blood. We further identified several factors and conditions susceptible to affect the accuracy of the measurement. Finally, we investigated the influence of the EIT sensor belt position on the measured heart signal. We observed that small belt displacements - likely to occur in clinical settings during patient handling - can induce errors of up to 30 mL on stroke volume estimation. In a second phase, we investigated the feasibility of a novel method for the non-invasive measurement of PAP by EIT. The method is based on the physiological relation linking the PAP to the velocity of propagation of the pressure waves in the pulmonary arteries. We hypothesized that the variations of this velocity, and therefore of the PAP, could be measured by EIT. In a bioimpedance model of the human thorax, we demonstrated the feasibility of our method in various types of pulmonary hypertensive disorders. Our EIT-derived parameter has shown to be particularly well-suited for predicting early changes in pulmonary hemodynamics due to its physiological link with arterial compliance. Finally, we validated experimentally our method in 14 subjects undergoing hypoxia-induced PAP changes. Significant correlation coefficients (range: [0.70, 0.98], average: 0.89) and small standard errors of the estimate (range: [0.9, 6.3] mmHg, average: 2.4 mmHg) were found between our EIT-derived systolic PAP and reference systolic PAP values obtained by Doppler echocardiography. In conclusion, there is a promising outlook for EIT in non-invasive hemodynamic monitoring. Our observations provide novel insights for the interpretation and understanding of EIT heart signals, and detail the physiological and metrological requirements for an accurate measurement of CO by EIT. Our novel PAP monitoring method, validated in vivo, allows a reliable tracking of PAP changes, thereby paving the way towards the development of a new branch of non-invasive hemodynamic monitors based on the use of EIT

Separating ventricular activity in thoracic EIT using 4D image-based FEM simulations

One challenge in central hemodynamic monitoring based on electrical impedance tomography (EIT) is to robustly detect ventricular signal components and the corresponding EIT image region without external monitoring information. Current stimulation and voltage measurement of EIT were simulated with finite element porcine torso models in presence of a multitude ofthoracic blood volume shifts. The simulated measurement data was examined for linear dependence on changes in stroke volume. Based onthe results the EIT measurement information regardingstroke volume changesis sparse