High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction

<p>Abstract</p> <p>Background</p> <p>Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death.</p> <p>Methods</p> <p>A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for <it>in vivo </it>treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for <it>in vivo </it>experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation.</p> <p>Results</p> <p>No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain.</p> <p>Conclusions</p> <p>H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.</p

Robust Adaptive Neurocontrol of SISO Nonlinear Systems Preceded by Unknown Deadzone

In this study, the problem of controlling an unknown SISO nonlinear system in Brunovsky canonical form with unknown deadzone input in such a way that the system output follows a specified bounded reference trajectory is considered. Based on universal approximation property of the neural networks, two schemes are proposed to handle this problem. The first scheme utilizes a smooth adaptive inverse of the deadzone. By means of Lyapunov analyses, the exponential convergence of the tracking error to a bounded zone is proven. The second scheme considers the deadzone as a combination of a linear term and a disturbance-like term. Thus, the estimation of the deadzone inverse is not required. By using a Lyapunov-like analyses, the asymptotic converge of the tracking error to a bounded zone is demonstrated. Since this control strategy requires the knowledge of a bound for an uncertainty/disturbance term, a procedure to find such bound is provided. In both schemes, the boundedness of all closed-loop signals is guaranteed. A numerical experiment shows that a satisfactory performance can be obtained by using any of the two proposed controllers

Rheological characterization of culture broth containing the exopolysaccharide PS-EDIV from Sphingomonas pituitosa

Sphingomonas pituitosa excretes the capsular exopolysaccharide PS-EDIV into the culture broth augmenting considerably its fluid viscosity. Since this change particularly affects key processes like mixing and transport during the microbial production, this work was aimed at the rheological characterization of the polymer-containing culture broth of S. pituitosa. The study included investigations on basic properties of the culture broth, but also on the dependence of the biomass-polymer-solution properties on different physicochemical post-cultivation treatment steps like variations of temperature, pH-value or concentration of salts. The essential result is the characterization of the viscoelastic behavior of the culture broth, which was more gel-like than sol-like and exhibited slight elastic properties. This rheological behavior showed that the PS-EDIV culture broth formed non-Newtonian fluids, indicating that it is a pseudoplastic biopolymer, with yield stress appearance and exhibits thixotropic properties. Rheograms were fitted to the Herschel-Bulkley model. The amplitude sweep revealed a deformation of 21% as the limiting value of the linear viscoelastic interval. Furthermore, the PS-EDIV culture broth showed a high viscosity which was strongly influenced by salt type and concentration but weakly influenced by temperature and pH-value within the investigated experimental boundaries. © 2009 Elsevier B.V. All rights reserved