A toy model of fractal glioma development under RF electric field treatment

A toy model for glioma treatment by a radio frequency electric field is suggested. This low-intensity, intermediate-frequency alternating electric field is known as the tumor-treating-field (TTF). In the framework of this model the efficiency of this TTF is estimated, and the interplay between the TTF and the migration-proliferation dichotomy of cancer cells is considered. The model is based on a modification of a comb model for cancer cells, where the migration-proliferation dichotomy becomes naturally apparent. Considering glioma cancer as a fractal dielectric composite of cancer cells and normal tissue cells, a new effective mechanism of glioma treatment is suggested in the form of a giant enhancement of the TTF. This leads to the irreversible electroporation that may be an effective non-invasive method of treating brain cancer.Comment: Submitted for publication in European Physical Journal

Non Thermal Irreversible Electroporation: Novel Technology for Vascular Smooth Muscle Cells Ablation

Non thermal Irreversible electroporation (NTIRE) is a new tissue ablation method that induces selective damage only to the cell membrane while sparing all other tissue components. Our group has recently showed that NTIRE attenuated neointimal formation in rodent model. The goal of this study was to determine optimal values of NTIRE for vascular smooth muscle cell (VSMC) ablation.33 Sprague-Dawley rats were used to compare NTIRE protocols. Each animal had NTIRE applied to its left common carotid artery using a custom-made electrodes. The right carotid artery was used as control. Electric pulses of 100 microseconds were used. Eight IRE protocols were compared: 1-4) 10 pulses at a frequency of 10 Hz with electric fields of 3500, 1750, 875 and 437.5 V/cm and 5-8) 45 and 90 pulses at a frequency of 1 Hz with electric fields of 1750 and 875 V/cm. Animals were euthanized after one week. Histological analysis included VSMC counting and morphometry of 152 sections. Selective slides were stained with elastic Van Gieson and Masson trichrome to evaluate extra-cellular structures. The most efficient protocols were 10 pulses of 3500 V/cm at a frequency of 10 Hz and 90 pulses of 1750 V/cm at a frequency of 1 Hz, with ablation efficiency of 89+/-16% and 94+/-9% respectively. Extra-cellular structures were not damaged and the endothelial layer recovered completely.NTIRE is a promising, efficient and simple novel technology for VMSC ablation. It enables ablation within seconds without causing damage to extra-cellular structures, thus preserving the arterial scaffold and enabling endothelial regeneration. This study provides scientific information for future anti-restenosis experiments utilizing NTIRE

The Effects of Irreversible Electroporation (IRE) on Nerves

Background: If a critical nerve is circumferentially involved with tumor, radical surgery intended to cure the cancer must sacrifice the nerve. Loss of critical nerves may lead to serious consequences. In spite of the impressive technical advancements in nerve reconstruction, complete recovery and normalization of nerve function is difficult to achieve. Though irreversible electroporation (IRE) might be a promising choice to treat tumors near or involved critical nerve, the pathophysiology of the nerve after IRE treatment has not be clearly defined. Methods: We applied IRE directly to a rat sciatic nerve to study the long term effects of IRE on the nerve. A sequence of 10 square pulses of 3800 V/cm, each 100 ms long was applied directly to rat sciatic nerves. In each animal of group I (IRE) the procedure was applied to produce a treated length of about 10 mm. In each animal of group II (Control) the electrodes were only applied directly on the sciatic nerve for the same time. Electrophysiological, histological, and functional studies were performed on immediately after and 3 days, 1 week, 3, 5, 7 and 10 weeks following surgery. Findings: Electrophysiological, histological, and functional results show the nerve treated with IRE can attain full recovery after 7 weeks. Conclusion: This finding is indicative of the preservation of nerve involving malignant tumors with respect to the application of IRE pulses to ablate tumors completely. In summary, IRE may be a promising treatment tool for any tumor involving nerves

Measurement of the cross-section ratio sigma_{psi(2S)}/sigma_{J/psi(1S)} in deep inelastic exclusive ep scattering at HERA

The exclusive deep inelastic electroproduction of $\psi(2S)$ and $J/\psi(1S)$ at an $ep$ centre-of-mass energy of 317 GeV has been studied with the ZEUS detector at HERA in the kinematic range $2 < Q^2 < 80$ GeV$^2$, $30 < W < 210$ GeV and $|t| < 1$ GeV$^2$, where $Q^2$ is the photon virtuality, $W$ is the photon-proton centre-of-mass energy and $t$ is the squared four-momentum transfer at the proton vertex. The data for $2 < Q^2 < 5$ GeV$^2$ were taken in the HERA I running period and correspond to an integrated luminosity of 114 pb$^{-1}$. The data for $5 < Q^2 < 80$ GeV$^2$ are from both HERA I and HERA II periods and correspond to an integrated luminosity of 468 pb$^{-1}$. The decay modes analysed were $\mu^+\mu^-$ and $J/\psi(1S) \,\pi^+\pi^-$ for the $\psi(2S)$ and $\mu^+\mu^-$ for the $J/\psi(1S)$. The cross-section ratio $\sigma_{\psi(2S)}/\sigma_{J/\psi(1S)}$ has been measured as a function of $Q^2, W$ and $t$. The results are compared to predictions of QCD-inspired models of exclusive vector-meson production.Comment: 24 pages, 8 figure

High-E_T dijet photoproduction at HERA

The cross section for high-E_T dijet production in photoproduction has been measured with the ZEUS detector at HERA using an integrated luminosity of 81.8 pb-1. The events were required to have a virtuality of the incoming photon, Q^2, of less than 1 GeV^2 and a photon-proton centre-of-mass energy in the range 142 < W < 293 GeV. Events were selected if at least two jets satisfied the transverse-energy requirements of E_T(jet1) > 20 GeV and E_T(jet2) > 15 GeV and pseudorapidity requirements of -1 < eta(jet1,2) < 3, with at least one of the jets satisfying -1 < eta(jet) < 2.5. The measurements show sensitivity to the parton distributions in the photon and proton and effects beyond next-to-leading order in QCD. Hence these data can be used to constrain further the parton densities in the proton and photon.Comment: 36 pages, 13 figures, 20 tables, including minor revisions from referees. Accepted by Phys. Rev.

Measurement of neutral current e+/-p cross sections at high Bjorken x with the ZEUS detector

The neutral current e+/-p cross section has been measured up to values of Bjorken x of approximately 1 with the ZEUS detector at HERA using an integrated luminosity of 187 inv. pb of e-p and 142 inv. pb of e+p collisions at sqrt(s) = 318GeV. Differential cross sections in x and Q2, the exchanged boson virtuality, are presented for Q2 geq 725GeV2. An improved reconstruction method and greatly increased amount of data allows a finer binning in the high-x region of the neutral current cross section and leads to a measurement with much improved precision compared to a similar earlier analysis. The measurements are compared to Standard Model expectations based on a variety of recent parton distribution functions.Comment: 39 pages, 9 figure

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