Monopole patch antenna for in vivo exposure to nanosecond pulsed electric fields.

To explore the promising therapeutic applications of short nanosecond electric pulses, in vitro and in vivo experiments are highly required. In this paper, an exposure system based on monopole patch antenna is reported to perform in vivo experiments on newborn mice with both monopolar and bipolar nanosecond signals. Analytical design and numerical simulations of the antenna in air were carried out as well as experimental characterizations in term of scattering parameter (S 11) and spatial electric field distribution. Numerical dosimetry of the setup with four newborn mice properly placed in proximity of the antenna patch was carried out, exploiting a matching technique to decrease the reflections due to dielectric discontinuities (i.e., from air to mouse tissues). Such technique consists in the use of a matching dielectric box with dielectric permittivity similar to those of the mice. The average computed electric field inside single mice was homogeneous (better than 68 %) with an efficiency higher than 20 V m-1 V-1 for the four exposed mice. These results demonstrate the possibility of a multiple (four) exposure of small animals to short nanosecond pulses (both monopolar and bipolar) in a controlled and efficient way.

Scenarios approach to the electromagnetic exposure: the case study of a train compartment.

Previous studies identified the train compartment as the place where people can experience the highest exposure levels (still below the international guideline limits) to electromagnetic fields in the radiofrequency range. Here a possible scenario of a train compartment has been reproduced and characterized, both numerically and experimentally. A good agreement between the simulated electric field distributions and measurements has been found. Results indicate that the higher values of exposure in specific positions inside the train compartment depend on the number of active cell phones, the bad coverage condition, the cell orientation, and the presence of metallic walls. This study shows that the proposed approach, based on the scenarios characterization, may efficiently support the assessment of the individual electromagnetic exposure.

A numerical study to compare stimulations by intraoperative microelectrodes and chronic macroelectrodes in the DBS technique.

Deep brain stimulation is a clinical technique for the treatment of parkinson's disease based on the electric stimulation, through an implanted electrode, of specific basal ganglia in the brain. To identify the correct target of stimulation and to choose the optimal parameters for the stimulating signal, intraoperative microelectrodes are generally used. However, when they are replaced with the chronic macroelectrode, the effect of the stimulation is often very different. Here, we used numerical simulations to predict the stimulation of neuronal fibers induced by microelectrodes and macroelectrodes placed in different positions with respect to each other. Results indicate that comparable stimulations can be obtained if the chronic macroelectrode is correctly positioned with the same electric center of the intraoperative microelectrode. Otherwise, some groups of fibers may experience a completely different electric stimulation.

Novel passive element circuits for microdosimetry of nanosecond pulsed electric fields.

Microdosimetric models for biological cells have assumed increasing significance in the development of nanosecond pulsed electric field technology for medical applications. In this paper, novel passive element circuits, able to take into account the dielectric dispersion of the cell, are provided. The circuital analyses are performed on a set of input pulses classified in accordance with the current literature. Accurate data in terms of transmembrane potential are obtained in both time and frequency domains for different cell models. In addition, a sensitivity study of the transfer function for the cell geometrical and dielectric parameters has been carried out. This analysis offers a new, simple, and efficient tool to characterize the nsPEFs' action at the cellular level.

Effects of nanosecond pulsed electric fields on the activity of a Hodgkin and Huxley neuron model.

The cell membrane poration is one of the main assessed biological effects of nanosecond pulsed electric fields (nsPEF). This structural change of the cell membrane appears soon after the pulse delivery and lasts for a time period long enough to modify the electrical activity of excitable membranes in neurons. Inserting such a phenomenon in a Hodgkin and Huxley neuron model by means of an enhanced time varying conductance resulted in the temporary inhibition of the action potential generation. The inhibition time is a function of the level of poration, the pore resealing time and the background stimulation level of the neuron. Such results suggest that the neuronal activity may be efficiently modulated by the delivery of repeated pulses. This opens the way to the use of nsPEFs as a stimulation technique alternative to the conventional direct electric stimulation for medical applications such as chronic pain treatment.

Signal transduction on enzymes: the effect of electromagnetic field stimuli on superoxide dismutase (SOD).

Protein functions and characteristics can highly differ from physiological conditions in presence of chemical, mechanical or electromagnetic stimuli. In this work we provide a rigorous picture of electric field effects on proteins behavior investigating, at atomistic details, the possible ways in which an external signal can be transduced into biochemical effects. Results from molecular dynamics (MD) simulations of a single superoxidismutase (SOD) enzyme in presence of high exogenous alternate electric fields will be discussed.

Micro vs macro electrode DBS stimulation: A dosimetric study.

Deep Brain Stimulation (DBS) is a clinically suitable technique for the treatment of the Parkinson's disease. Recently, also other neurological disorders such as Tourette syndrome, obsessive-compulsive disorder, epilepsy are being to be treated with DBS. However, the debate on its therapeutic mechanisms of action is still open. In order to a better understanding of such mechanisms, in this work the attention is focused on the DBS micro-stimulation. Indeed, a micro electrodes registration and stimulation is a fundamental step, during the surgical phase, to optimize the technique in terms of DBS lead positioning and DBS signal parameters. In this paper a dosimetric analysis with micro electrodes has been carried out, showing a more focused distribution of the electrical potential induced in the neuroanatomical tissues and changes of the excited/inhibited regions, respect to a macro electrodes stimulation.

Channel noise enhances signal detectability in a model of acoustic neuron through the stochastic resonance paradigm.

A number of experimental investigations have evidenced the extraordinary sensitivity of neuronal cells to weak input stimulations, including electromagnetic (EM) fields. Moreover, it has been shown that biological noise, due to random channels gating, acts as a tuning factor in neuronal processing, according to the stochastic resonant (SR) paradigm. In this work the attention is focused on noise arising from the stochastic gating of ionic channels in a model of Ranvier node of acoustic fibers. The small number of channels gives rise to a high noise level, which is able to cause a spike train generation even in the absence of stimulations. A SR behavior has been observed in the model for the detection of sinusoidal signals at frequencies typical of the speech.

Fundamental electrical quantities in deep brain stimulation: influence of domain dimensions and boundary conditions.

Deep Brain Stimulation (DBS) has revealed a convincing clinical efficacy in Parkinson's diseases and essential tremor. Unfortunately, to date no clear understanding of the therapeutic mechanisms has been achieved. Characterization of the distribution of the electrical quantities inside the target areas of the central nervous system is one fundamental step ahead. Starting from the studies that so far addressed this issue, aim of this work is to quantify the role of some parameters, such as dimensions of the conducting domain and of boundary conditions, on the distribution of the fundamental electric quantities inside the brain target area.

Effects of an exogenous noise on a realistic network model: encoding of an EM signal.

Endogenous noise has been shown to play a central role in the detection of an electromagnetic signal in the nervous system. In this work, following a biomedical perspective, an exogenous noise applied to a realistic feedforward network model has been considered. It will be shown that, if the exogenous noise is properly filtered and its level is adjusted, a clear optimization of network encoding of an electromagnetic signal, representative of an external stimulation, is obtained through the stochastic resonance paradigm.

Comparison between low-level 50 Hz and 900 MHz electromagnetic stimulation on single channel ionic currents and on firing frequency in dorsal root ganglion isolated neurons.

Alteration of membrane surface charges represents one of the most interesting effects of the electromagnetic exposure on biological structures. Some evidence exists in the case of extremely low frequency whereas the same effect in the radiofrequency range has not been detected. Changes in transmembrane voltages are probably responsible for the mobilization of intracellular calcium described in some previous studies but not confirmed in others. These controversial results may be due to the cell type under examination and/or to the permeability properties of the membranes. According to such a hypothesis, calcium oscillations would be a secondary effect due to the induced change in the membrane voltage and thus dependent on the characteristics of ionic channels present in a particular preparation. Calcium increases could suggest more than one mechanism to explain the biological effects of exposure due to the fact that all the cellular pathways using calcium ions as a second messenger could be, in theory, disturbed by the electromagnetic field exposure. In the present work, we investigate the early phase of the signal transmission in the peripheral nervous system. We present evidence that the firing rate of rat sensory neurons can be modified by 50/60 Hz magnetic field but not by low level 900 MHz fields. The action of the 50/60 Hz magnetic field is biphasic. At first, the number of action potentials increases in time. Following this early phase, the firing rate decreases more rapidly than in control conditions. The explanation can be found at the single-channel level. Dynamic action current recordings in dorsal root ganglion neurons acutely exposed to the electromagnetic field show increased functionality of calcium channels. In parallel, a calcium-activated potassium channel is able to increase its mean open time.

Effects of exogenous noise in a silent neuron model: firing induction and em signal detection.

Neuronal intrinsic noise has already shown to play a constructive role in stimuli detection. Here, an exogenous noise, applied to the neuron model as a random membrane voltage perturbation, has been considered. Properly choosing its frequency band, such a noise is able to induce firing activity in a silent neuron and to enhance the detectability of an exogenous signal, representative of an electromagnetic stimulation, through the phenomenon known as stochastic resonance.