Dielectric Spectroscopy Shows a Permittivity Contrast between Meningioma Tissue and Brain White and Gray Matter-A Potential Physical Biomarker for Meningioma Discrimination.

The effectiveness of surgical resection of meningioma, the most common primary CNS tumor, depends on the capability to intraoperatively discriminate between the meningioma tissue and the surrounding brain white and gray matter tissues. Aiming to find a potential biomarker based on tissue permittivity, dielectric spectroscopy of meningioma, white matter, and gray matter ex vivo tissues was performed using the open-ended coaxial probe method in the microwave frequency range from 0.5 to 18 GHz. The averages and the 95% confidence intervals of the measured permittivity for each tissue were compared. The results showed the absence of overlap between the 95% confidence intervals for meningioma tissue and for brain white and gray matter, indicating a significant difference in average permittivity (p ≤ 0.05) throughout almost the entire measured frequency range, with the most pronounced contrast found between 2 GHz and 5 GHz. The discovered contrast is relevant as a potential physical biomarker to discriminate meningioma tissue from the surrounding brain tissues by means of permittivity measurement, e.g., for intraoperative meningioma margin assessment. The permittivity models for each tissue, developed in this study as its byproducts, will allow more accurate electromagnetic modeling of brain tumor and healthy tissues, facilitating the development of new microwave-based medical devices and tools.

The Effect of Freezing and Thawing on Complex Permittivity of Bovine Tissues.

The aim of this study was to investigate how the freezing and thawing of biological tissues affect their complex permittivity in the microwave frequency range from 0.5 MHz to 18 GHz. We measured the complex permittivity of ex vivo bovine tissues, including brain white and grey matter, liver, and muscle, using an open-ended coaxial probe. Bovine tissues were chosen for their availability and similarity to human tissue permittivity. The samples were measured at 25 °C, before they were frozen either in a commercial freezer below -18 °C or in liquid nitrogen, nominally at -196 °C. The measured permittivity before freezing was compared to the permittivity measured after freezing and thawing the tissues back to 25 °C. Statistical analysis of the results showed a statistically significant change in permittivity after freezing and thawing by both methods for all the measured tissues, at least in some parts of the measured frequency range. The largest difference was observed for the white matter, while the liver had the smallest percent change.

Complex Permittivity of Ex-Vivo Human, Bovine and Porcine Brain Tissues in the Microwave Frequency Range.

Accurate knowledge about the dielectric properties of biological tissues in the microwave frequency range may lead to advancement of biomedical applications based on microwave technology. However, the published data are very scarce, especially for human brain tissues. The aim of this work was to measure and report the complex permittivity of brain white matter, grey matter and cerebellum. Complex permittivity was measured on human, bovine and porcine brain tissues in the microwave frequency range from 0.5 to 18 GHz using an open-ended coaxial probe. The results present a valuable addition to the available data on the brain tissue complex permittivity. Some noticeable variations between the results lead to several conclusions. Complex permittivity variation within the same tissue type of the individual species was comparable to interspecies variation. The difference was prominent between human brains obtained from autopsies, while bovine brains obtained from healthy animals showed very similar complex permittivity. We hypothesize that the difference might have been caused by the basic pathologies of the patients, where the associated therapies could have affected the brain water content. We also examined the effect of excised tissue degradation on its complex permittivity over the course of three days, and the results suggest the gradual dehydration of the samples.

Dielectric Permittivity Measurement Using Open-Ended Coaxial Probe-Modeling and Simulation Based on the Simple Capacitive-Load Model.

The study aim was to validate that dielectric permittivity measurement using the open-ended coaxial probe can be reliably modeled using electromagnetic modeling and simulations, followed by the postprocessing calculations based on the simple capacitive-load model. Saline solutions with various NaCl concentrations were used as materials under test (MUTs) to investigate how ionic conductivity affects the model validity. Two different solvers and simulation methods were used: FEKO for the frequency domain and CST for the time domain. Furthermore, we performed physical experiments with the same probe and MUTs, again implementing the capacitive-load model on the measurement data to observe the model validity. Relative error of the capacitive-load model with respect to the reference permittivity values, both in measurements and simulations, was within 10% for all cases except for the measured εr' of 1M solution at the lowest frequencies. The model yielded average relative errors well below 1% for the physiological saline, which is relevant for biological materials. The error increased for higher concentrations and for the lowest simulated frequencies but was within the declared measurement accuracy of the probe itself. This makes the simple capacitive-load model valid for all analyzed concentrations in the microwave frequency range from 0.5 to 18 GHz.

Implantable, Programmable, and Wireless Device for Electrical Stimulation of the Dorsal Root Ganglion in Freely-Moving Rats: A Proof of Concept Study.

OBJECTIVE: This was a proof of concept study, based on systematic reviews of the efficacy and safety of the dorsal root ganglion (DRG) stimulation. The main objective was to develop an implantable, programmable, and wireless device for electrical stimulation of DRG and a methodology that can be used in translational research, especially to understand the mechanism of neuromodulation and to test new treatment modalities in animal models of pain. METHODS: We developed and tested a stimulator that uses a battery-powered microelectronic circuit, to generate constant current square biphasic or monophasic pulsed waveform of variable amplitudes and duration. It is controlled by software and an external controller that allows radio frequency communication with the stimulator. The stimulator was implanted in Sprague-Dawley (SD) rats. The lead was positioned at the L5 DRG level, while the stimulator was placed in the skin pocket at the ipsilateral side. Forty-five animals were used and divided into six groups: spinal nerve ligation (SNL), chronic compression injury of the DRG (CCD), SNL + active DRG stimulation, intact control group, group with the implanted sham stimulator, and sham lead. Behavioral testing was performed on the day preceding surgery and three times postoperatively (1st, 3rd, and 7th day). RESULTS: In animals with SNL, neurostimulation reduced pain-related behavior, tested with pinprick hyperalgesia, pinprick withdrawal test, and cold test, while the leads per se did not cause DRG compression. The rats well tolerated the stimulator. It did not hinder animal movement, and it enabled the animals to be housed under regular conditions. CONCLUSION: A proof-of-concept experiment with our stimulator verified the usability of the device. The stimulator enables a wide range of research applications from adjusting stimulation parameters for different pain conditions, studying new stimulation methods with different frequencies and waveforms to obtain knowledge about analgesic mechanisms of DRG stimulation.

Current Directions in the Auricular Vagus Nerve Stimulation II - An Engineering Perspective.

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging electroceutical technology in the field of bioelectronic medicine with applications in therapy. Artificial modulation of the afferent vagus nerve - a powerful entrance to the brain - affects a large number of physiological processes implicating interactions between the brain and body. Engineering aspects of aVNS determine its efficiency in application. The relevant safety and regulatory issues need to be appropriately addressed. In particular, in silico modeling acts as a tool for aVNS optimization. The evolution of personalized electroceuticals using novel architectures of the closed-loop aVNS paradigms with biofeedback can be expected to optimally meet therapy needs. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the scope of EU COST Action "European network for innovative uses of EMFs in biomedical applications (BM1309)." Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on engineering aspects - a discussion of physiological aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Current Directions in the Auricular Vagus Nerve Stimulation I - A Physiological Perspective.

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action "European network for innovative uses of EMFs in biomedical applications (BM1309)." Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects - a discussion of engineering aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Assessment of cytogenetic damage and oxidative stress in personnel occupationally exposed to the pulsed microwave radiation of marine radar equipment.

Due to increased usage of microwave radiation, there are concerns of its adverse effect in today's society. Keeping this in view, study was aimed at workers occupationally exposed to pulsed microwave radiation, originating from marine radars. Electromagnetic field strength was measured at assigned marine radar frequencies (3 GHz, 5.5 GHz and 9.4 GHz) and corresponding specific absorption rate values were determined. Parameters of the comet assay and micronucleus test were studied both in the exposed workers and in corresponding unexposed subjects. Differences between mean tail intensity (0.67 vs. 1.22) and moment (0.08 vs. 0.16) as comet assay parameters and micronucleus test parameters (micronuclei, nucleoplasmic bridges and nuclear buds) were statistically significant between the two examined groups, suggesting that cytogenetic alterations occurred after microwave exposure. Concentrations of glutathione and malondialdehyde were measured spectrophotometrically and using high performance liquid chromatography. The glutathione concentration in exposed group was significantly lower than in controls (1.24 vs. 0.53) whereas the concentration of malondialdehyde was significantly higher (1.74 vs. 3.17), indicating oxidative stress. Results suggests that pulsed microwaves from working environment can be the cause of genetic and cell alterations and that oxidative stress can be one of the possible mechanisms of DNA and cell damage.

Comparison of 864 MHz and 935 MHz microwave radiation effects on cell culture.

The objective of this study was to compare the effects of 864 MHz and 935 MHz radiofrequency/microwave radiation on the ability of V79 cells to proliferate, form colonies and on their viability. For one, two and three hours, the cells were exposed to the 864 MHz field in a transversal electromagnetic mode cell (TEM) connected with amplifier and to the 935 MHz field in a gigahertz transversal electromagnetic mode cell (GTEM) equipped with a signal generator. The average specific absorption rate (SAR) was 0.08 W kg(-1) for the 864 MHz field and 0.12 W kg(-1) for the 935 MHz field. In comparison to the control cell samples, the growth curve of the 864 MHz irradiated cells showed a significant decrease after two-hour and three-hour exposure on the Day 3 after exposure. Likewise, cells exposed to 935 MHz microwaves for three hours showed a significant growth on Day 3 after exposure. The colony-forming ability and viability of cells exposed to 864 MHz and 935 MHz microwaves did not significantly differ from the matched controls. The applied RF/MW fields showed a similar effect on cell culture growth, colony-forming ability and viability of V79 cells.