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.

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.

We produced an anatomically and dielectrically realistic phantom of the axillary region to enable the experimental assessment of Axillary Lymph Node (ALN) imaging using microwave imaging technology. We segmented a thoracic Computed Tomography (CT) scan and created a computer-aided designed file containing the anatomical configuration of the axillary region. The phantom comprises five 3D-printed parts representing the main tissues of interest of the axillary region for the purpose of microwave imaging: fat, muscle, bone, ALNs, and lung. The phantom allows the experimental assessment of multiple anatomical configurations, by including ALNs of different size, shape, and number in several locations. Except for the bone mimicking organ, which is made of solid conductive polymer, we 3D-printed cavities to represent the fat, muscle, ALN, and lung and filled them with appropriate tissue-mimicking liquids. Existing studies about complex permittivity of ALNs have reported limitations. To address these, we measured the complex permittivity of both human and animal lymph nodes using the standard open-ended coaxial-probe technique, over the 0.5 GHz–8.5 GHz frequency band, thus extending current knowledge on dielectric properties of ALNs. Lastly, we numerically evaluated the effect of the polymer which constitutes the cavities of the phantom and compared it to the realistic axillary region. The results showed a maximum difference of 7 dB at 4 GHz in the electric field magnitude coupled to the tissues and a maximum of 10 dB difference in the ALN response. Our results showed that the phantom is a good representation of the axillary region and a viable tool for pre-clinical assessment of microwave imaging technology.

Achieving a better characterization of human blood conductivity is of high relevance for medical applications. In this study we measured the complex impedance of N = 10 human whole blood samples (from N = 10 oncology patients) at room temperature (T = 22.6 ± 0.8 • C) and at body temperature (T = 36.6 ± 0.4 • C). The complex impedance was measured using the measurement setup consisting of a custom made four-electrode probe and a commercially available galvanostat. The measured complex impedance data were used to calculate the conductivity of whole blood over the 631 Hz-100 kHz frequency range. The calculated conductivity data is presented and was compared with the literature data. The data from our study is in good agreement with the data available in the literature. Additionally, full blood counts were provided for N = 8 samples and Pearson correlation coefficient was calculated between the conductivity and blood counts at different frequencies. The three blood count parameters with the highest correlation coefficient are haematocrit (Hct), haemoglobin (Hgb) and red cell count (RBC). The correlation coefficient was shown to decrease as the frequency increases and was the highest at f = 631 Hz, which is the lowest reported frequency. To our knowledge this is the first study to measure low-frequency (i.e. below 1 MHz) conductivity of whole human blood at body temperature using the four-electrode technique. The results of this study represent an important contribution to the literature, which is currently limited in this area and will help further medical device design.

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Accurate knowledge of the dielectric properties of biological tissues is important in dosimetry studies and for medical diagnostic, monitoring and therapeutic technologies. In particular, the dielectric properties of the heart are used in numerical simulations of radiofrequency and microwave heart ablation. In one recent study, it was demonstrated that the dielectric properties of different components of the heart can vary considerably, contrary to previous literature that treated the heart as a homogeneous organ with measurements that ignored the anatomical location. Therefore, in this study, we record and report the dielectric properties of the heart as a heterogeneous organ. We measured the dielectric properties at different locations inside and outside of the heart over the 500 MHz to 20 GHz frequency range. Different parts of the heart were identified based on the anatomy of the heart and their function; they include the epicardium, endocardium, myocardium, exterior and interior surfaces of atrial appendage, and the luminal surface of the great vessels. The measured dielectric properties for each part of the heart are reported at both a single frequency (2.4 GHz), which is of interest in microwave medical applications, and as parameters of a broadband Debye model. The results show that in terms of dielectric properties, different parts of the heart should not be considered the same, with more than 25% difference in dielectric properties between some parts. The specific Debye models and single frequency dielectric properties from this study can be used to develop more detailed models of the heart to be used in electromagnetic modeling.

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Electrical conductivity of blood at low frequencies is fundamental for medical electromagnetic applications, such as pulsed field ablation of cardiac tissue. There are several studies in the literature reporting conductivity measurements of blood. However, knowledge of this data at frequencies below 100 kHz is limited due to measurement challenges, including electrode polarization. Electrode polarization is generally reduced by using a four-electrode probe method. For this reason, in this study, we used a low-cost four-electrode probe to measure the conductivity of N=9 human blood samples to electrically characterize human blood between 100 Hz and 100 kHz. The measured conductivity data is in good agreement with the data from the literature, showing that such a low-cost probe is suitable for measurements of blood conductivity. This study introduces a simple and low-cost four-electrode probe as a practical tool for measurements of electrical conductivity of human blood at lower frequencies and helps to fill the gap in the knowledge of electrical conductivity of human blood.