Assessment of Intestinal Ischemia-Reperfusion Injury Using Diffuse Reflectance VIS-NIR Spectroscopy and Histology.

A porcine model was used to investigate the feasibility of using VIS-NIR spectroscopy to differentiate between degrees of ischemia-reperfusion injury in the small intestine. Ten pigs were used in this study and four segments were created in the small intestine of each pig: (1) control, (2) full arterial and venous mesenteric occlusion for 8 h, (3) arterial and venous mesenteric occlusion for 2 h followed by reperfusion for 6 h, and (4) arterial and venous mesenteric occlusion for 4 h followed by reperfusion for 4 h. Two models were built using partial least square discriminant analysis. The first model was able to differentiate between the control, ischemic, and reperfused intestinal segments with an average accuracy of 99.2% with 10-fold cross-validation, and the second model was able to discriminate between the viable versus non-viable intestinal segments with an average accuracy of 96.0% using 10-fold cross-validation. Moreover, histopathology was used to investigate the borderline between viable and non-viable intestinal segments. The VIS-NIR spectroscopy method together with a PLS-DA model showed promising results and appears to be well-suited as a potentially real-time intraoperative method for assessing intestinal ischemia-reperfusion injury, due to its easy-to-use and non-invasive nature.

A CMOS Multi-Electrode Array for Four-Electrode Bioimpedance Measurements.

This work demonstrates how a multi-electrode array (MEA) dedicated to four-electrode bioimpedance measurements can be implemented on a complementary metal-oxide-semiconductor (CMOS) chip. As a proof of concept, an 8 × 8 pixel array along with dedicated amplifiers was designed and fabricated in the TSMC 180 nm process. Each pixel in the array contains a circular current carrying (CC) electrode that can act as a current source or sink. In order to measure a differential voltage between the pixels, each CC electrode is surrounded by a ring shaped pick up (PU) electrode. The differential voltages can be measured by an on-board instrumentation amplifier, while the currents can be measured with an on-bard transimpedance amplifier. Openings in the passivation layer exposed the aluminum top metal layer, and a metal stack of zinc, nickel and gold was deposited in an electroless plating process. The chips were then wire bonded to a ceramic package and prepared for wet experiments by encapsulating the bonding wires and pads in the photoresist SU-8. Measurements in liquids with different conductivities were performed to demonstrate the functionality of the chip.

Utilization of dielectric properties for assessment of liver ischemia-reperfusion injury in vivo and during machine perfusion.

There is a shortage of donor livers and patients consequently die on waiting lists worldwide. Livers are discarded if they are clinically judged to have a high risk of non-function following transplantation. With the aim of extending the pool of available donor livers, we assessed the condition of porcine livers by monitoring the microwave dielectric properties. A total of 21 livers were divided into three groups: control with no injury (CON), biliary injury by hepatic artery occlusion (AHEP), and overall hepatic injury by static cold storage (SCS). All were monitored for four hours in vivo, followed by ex vivo plurithermic machine perfusion (PMP). Permittivity data was modeled with a two-pole Cole-Cole equation, and dielectric properties from one-hour intervals were analyzed during in vivo and normothermic machine perfusion (NMP). A clear increasing trend in the conductivity was observed in vivo in the AHEP livers compared to the control livers. After four hours of NMP, separations in the conductivity were observed between the three groups. Our results indicate that dielectric relaxation spectroscopy (DRS) can be used to detect and differentiate liver injuries, opening for a standardized and reliable point of evaluation for livers prior to transplantation.

Small intestinal viability assessment using dielectric relaxation spectroscopy and deep learning.

Intestinal ischemia is a serious condition where the surgeon often has to make important but difficult decisions regarding resections and resection margins. Previous studies have shown that 3 h (hours) of warm full ischemia of the small bowel followed by reperfusion appears to be the upper limit for viability in the porcine mesenteric ischemia model. However, the critical transition between 3 to 4 h of ischemic injury can be nearly impossible to distinguish intraoperatively based on standard clinical methods. In this study, permittivity data from porcine intestine was used to analyze the characteristics of various degrees of ischemia/reperfusion injury. Our results show that dielectric relaxation spectroscopy can be used to assess intestinal viability. The dielectric constant and conductivity showed clear differences between healthy, ischemic and reperfused intestinal segments. This indicates that dielectric parameters can be used to characterize different intestinal conditions. In addition, machine learning models were employed to classify viable and non-viable segments based on frequency dependent dielectric properties of the intestinal tissue, providing a method for fast and accurate intraoperative surgical decision-making. An average classification accuracy of 98.7% was obtained using only permittivity data measured during ischemia, and 96.2% was obtained with data measured during reperfusion. The proposed approach allows the surgeon to get accurate evaluation from the trained machine learning model by performing one single measurement on an intestinal segment where the viability state is questionable.

Automatic Prediction of Ischemia-Reperfusion Injury of Small Intestine Using Convolutional Neural Networks: A Pilot Study.

Acute intestinal ischemia is a life-threatening condition. The current gold standard, with evaluation based on visual and tactile sensation, has low specificity. In this study, we explore the feasibility of using machine learning models on images of the intestine, to assess small intestinal viability. A digital microscope was used to acquire images of the jejunum in 10 pigs. Ischemic segments were created by local clamping (approximately 30 cm in width) of small arteries and veins in the mesentery and reperfusion was initiated by releasing the clamps. A series of images were acquired once an hour on the surface of each of the segments. The convolutional neural network (CNN) has previously been used to classify medical images, while knowledge is lacking whether CNNs have potential to classify ischemia-reperfusion injury on the small intestine. We compared how different deep learning models perform for this task. Moreover, the Shapley additive explanations (SHAP) method within explainable artificial intelligence (AI) was used to identify features that the model utilizes as important in classification of different ischemic injury degrees. To be able to assess to what extent we can trust our deep learning model decisions is critical in a clinical setting. A probabilistic model Bayesian CNN was implemented to estimate the model uncertainty which provides a confidence measure of our model decisions.

Temperature dependence of the microwave dielectric properties of [Formula: see text]-aminobutyric acid.

The GABA molecule is the major inhibitory neurotransmitter in the mammalian central nervous system. Through binding to post-synaptic neurons, GABA reduces the neuronal excitability by hyperpolarization. Correct binding between the GABA molecules and its receptors relies on molecular recognition. Earlier studies suggest that recognition is determined by the geometries of the molecule and its receptor. We employed dielectric relaxation spectroscopy (DRS) to study the conformation and dielectric properties of the GABA molecule under physiologically relevant laboratory conditions. The dielectric properties of GABA investigated have given us new insights about the GABA molecule, such as how they interact with each other and with water molecules at different temperatures (22°C and 37.5°C). Higher temperature leads to lower viscosity, thus lower relaxation time. The change in the GABA relaxation time due to concentration change is more associated with the solution viscosity than with the GABA dipole moment. A resonance behavior was observed with high GABA concentrations at physiological temperature, where there might be a phase transition at a certain temperature for a given GABA concentration that leads to a sudden change of the dielectric properties.

Feasibility of Using Electrical Impedance Spectroscopy for Assessing Biological Cell Damage during Freezing and Thawing.

This study was performed to test bioimpedance as a tool to detect the effect of different thawing methods on meat quality to aid in the eventual creation of an electric impedance-based food quality monitoring system. The electric impedance was measured for fresh pork, thawed pork, and during quick and slow thawing. A clear difference was observed between fresh and thawed samples for both impedance parameters. Impedance was different between the fresh and the frozen-thawed samples, but there were no impedance differences between frozen-thawed samples and the ones that were frozen-thawed and then stored at +3 °C for an additional 16 h after thawing. The phase angle was also different between fresh and the frozen-thawed samples. At high frequency, there were small, but clear phase angle differences between frozen-thawed samples and the samples that were frozen-thawed and subsequently stored for more than 16 h at +3 °C. Furthermore, the deep learning model LSTM-RNN (long short-term memory recurrent neural network) was found to be a promising way to classify the different methods of thawing.

Simple circuit equivalents for the constant phase element.

The constant phase element (CPE) is a capacitive element with a frequency-independent negative phase between current and voltage which interpolates between a capacitor and a resistor. It is used extensively to model the complexity of the physics in e.g. the bioimpedance and electrochemistry fields. There is also a similar element with a positive phase angle, and both the capacitive and inductive CPEs are members of the family of fractional circuit elements or fractance. The physical meaning of the CPE is only partially understood and many consider it an idealized circuit element. The goal here is to provide alternative equivalent circuits, which may give rise to better interpretations of the fractance. Both the capacitive and the inductive CPEs can be interpreted in the time-domain, where the impulse and step responses are temporal power laws. Here we show that the current impulse responses of the capacitive CPE is the same as that of a simple time-varying series RL-circuit where the inductor's value increases linearly with time. Similarly, the voltage response of the inductive CPE corresponds to that of a simple parallel RC circuit where the capacitor's value increases linearly with time. We use the Micro-Cap circuit simulation program, which can handle time-varying circuits, for independent verification. The simulation corresponds exactly to the expected response from the proposed equivalents within 0.1% error. The realization with time-varying components correlates with known time-varying properties in applications, and may lead to a better understanding of the link between CPE and applications.

Correction: Dynamic modeling of soft continuum manipulators using lie group variational integration.

[This corrects the article DOI: 10.1371/journal.pone.0236121.].

Dynamic modeling of soft continuum manipulators using lie group variational integration.

This paper presents the derivation and experimental validation of algorithms for modeling and estimation of soft continuum manipulators using Lie group variational integration. Existing approaches are generally limited to static and quasi-static analyses, and are not sufficiently validated for dynamic motion. However, in several applications, models need to consider the dynamical behavior of the continuum manipulators. The proposed modeling and estimation formulation is obtained from a discrete variational principle, and therefore grants outstanding conservation properties to the continuum mechanical model. The main contribution of this article is the experimental validation of the dynamic model of soft continuum manipulators, including external torques and forces (e.g., generated by magnetic fields, friction, and the gravity), by carrying out different experiments with metal rods and polymer-based soft rods. To consider dissipative forces in the validation process, distributed estimation filters are proposed. The experimental and numerical tests also illustrate the algorithm's performance on a magnetically-actuated soft continuum manipulator. The model demonstrates good agreement with dynamic experiments in estimating the tip position of a Polydimethylsiloxane (PDMS) rod. The experimental results show an average absolute error and maximum error in tip position estimation of 0.13 mm and 0.58 mm, respectively, for a manipulator length of 60.55 mm.

Simulation based comparison between a transversal and a tangential memristor model with a capacitance in parallel.

In non-linear measurements, the applied stimulus itself affects the electrical properties of the underlying tissue. If corresponding voltage-current plots exhibit pinched hysteresis loops with pinched point in the origin of coordinates, the tissue can be classified as a memristor. Several organic memristors like human skin, venus flytrap and slime mould memristors have been demonstrated. However, measurements on organic memristors are usually affected by parasitic elements like a capacitance which will influence the appearance of the recorded pinched hysteresis loops. Here we study the parallel connection of two different memristor types, one with tangential and the other with transversal pinched hysteresis loop, and a capacitance by simulations. The simulations are inspired by human skin; beside the sweat ducts that can be modelled as a transversal memristor, the surrounding tissue, the stratum corneum exhibits non-linear electrical properties, as well. Based on a systematic study we suggested that the stratum corneum may be modelled as a tangential memristor. We demonstrate here by simulations that hysteresis loops with two pinched points can be achieved if a tangential memristor model is connected in parallel to a capacitance. Similar results were obtained from the skin recordings of some subjects; examples are presented here. Furthermore, if both the tangential and the transversal memristor models contribute to the simulation, quite asymmetric pinched hysteresis loops are obtained which are similar to recordings of some other test subjects.

Measuring Blood Pulse Wave Velocity with Bioimpedance in Different Age Groups.

In this project, we have studied the use of electrical impedance cardiography as a possible method for measuring blood pulse wave velocity, and hence be an aid in the assessment of the degree of arteriosclerosis. Using two different four-electrode setups, we measured the timing of the systolic pulse at two locations, the upper arm and the thorax, and found that the pulse wave velocity was in general higher in older volunteers and furthermore that it was also more heart rate dependent for older subjects. We attribute this to the fact that the degree of arteriosclerosis typically increases with age and that stiffening of the arterial wall will make the arteries less able to comply with increased heart rate (and corresponding blood pressure), without leading to increased pulse wave velocity. In view of these findings, we conclude that impedance cardiography seems to be well suited and practical for pulse wave velocity measurements and possibly for the assessment of the degree of arteriosclerosis. However, further studies are needed for comparison between this approach and reference methods for pulse wave velocity and assessment of arteriosclerosis before any firm conclusions can be drawn.

Bioimpedance and NIR for Non-invasive Assessment of Blood Glucose.

Sixteen volunteers each drank 700 ml sugar-containing soft drink during two successive periods and the blood sugar was measured at 10 min intervals together with electrical impedance spectroscopy and near infrared spectroscopy (NIR). A maximum correlation of 0.46 was found for the electrical measurements but no clear separation between low and high blood glucose levels were found in the NIR measurements. The latter was attributed to the experimental design where the NIR probe was removed from the skin between each measurement.

Comprehensive study of buffer systems and local pH effects in electromembrane extraction.

Different phosphate-, acetate- and formate buffers in the pH range 2.0-6.8 were tested for electromembrane extraction (EME) in a 96-well system. The five basic drugs haloperidol, loperamide, methadone, nortriptyline, and pethidine were selected as model analytes. The EME performance was tested with respect to extraction recovery, extraction current and pH-stability. The analytes were extracted from 200 µL buffer, through a 100 µm thick supported liquid membrane (SLM) of 2-nitrophenyl octyl ether (NPOE) immobilized in the pores of filters in a 96-well plate, and into 100 µL buffer acceptor phase. The extraction voltage was 50 V and the extraction time was 10 min. The acceptor phase was analyzed by HPLC-UV. The extraction current was ≤6 µA with all buffers, and pH was effectively stabilized during EME using buffers as donor (sample) and acceptor phase. For buffers with pH ≤ 4.8 as acceptor phase, the extraction recoveries were in the range 66-97% and with RSD <15%. With pH in the range 5.8-6.8 in the acceptor phase, the extraction recoveries decreased and were in the range 21-62%. This was attributed to elevated pH conditions in the acceptor/SLM interface. The presence of elevated pH conditions was visualized with phenolphthalein as pH sensitive color indicator. Increasing the buffer strength from 10 to 500 mM in an attempt to offset the elevated pH conditions gave no improvement, and elevated pH conditions remained. Elevated pH conditions in the acceptor/SLM interface were also observed when voltage was increased, and when NPOE was replaced with tributyl phosphate as SLM. The presence of elevated pH conditions close to the SLM in EME was discussed for the first time, and this information is highly important for future development of EME.

Bioimpedance monitoring of 3D cell culturing--complementary electrode configurations for enhanced spatial sensitivity.

A bioimpedance platform is presented as a promising tool for non-invasive real-time monitoring of the entire process of three-dimensional (3D) cell culturing in a hydrogel scaffold. In this study, the dynamics involved in the whole process of 3D cell culturing, starting from polymerisation of a bare 3D gelatin scaffold, to human mesenchymal stem cell (MSC) encapsulation and proliferation, was monitored over time. The platform consists of a large rectangular culture chamber with four embedded vertical gold plate electrodes that were exploited in two- and three terminal (2T and 3T) measurement configurations. By switching between the different combinations of electrode couples, it was possible to generate a multiplexing-like approach, which allowed for collecting spatially distributed information within the 3D space. Computational finite element (FE) analysis and electrochemical impedance spectroscopic (EIS) characterisation were used to determine the configurations' sensitivity field localisation. The 2T setup gives insight into the interfacial phenomena at both electrode surfaces and covers the central part of the 3D cell culture volume, while the four 3T modes provide focus on the dynamics at the corners of the 3D culture chamber. By combining a number of electrode configurations, complementary spatially distributed information on a large 3D cell culture can be obtained with maximised sensitivity in the entire 3D space. The experimental results show that cell proliferation can be monitored within the tested biomimetic environment, paving the way to further developments in bioimpedance tracking of 3D cell cultures and tissue engineering.

Wireless vital signs from a life-supporting medical device exposed to electromagnetic disturbance.

OBJECTIVES: To evaluate the level of agreement of simulated wired and Wi-Fi vital signs output from an intra-aortic balloon pump during exposure to electromagnetic interference from frequency overlapping ZigBee sensors. MATERIAL AND METHODS: A series of experiments with interference from single and multiple ZigBee sensors were benchmarked with wired and Wi-Fi output. Tests included single ZigBee sensor adjacent and co-channel interference, and multiple ZigBee interferences towards the Wi-Fi receiver and transmitter. RESULTS: Interference-free differences between wired and wireless aortic blood pressure and electrocardiogram were very small, verified by time domain and Bland - Altman plots. Bland - Altman plots comparing level of agreement in wired and wireless aortic blood pressure and ECG output during interference experiments showed a difference from 0.2 to 0.3 mmHg for blood pressure, and from 0.001 to 0.004 mV for electrocardiogram. CONCLUSIONS: Level of agreement in wired and wireless (Wi-Fi) arterial blood pressure and electrocardiogram during single or multiple sensor interference was high. No clinically relevant degradation of Wi-Fi transmission of aortic blood pressure or ECG signals was observed.