Tissue response of radiation therapy assessed by electrical impedance spectroscopy (EIS) in subcutaneous tumours in rats.

The present investigation aims to evaluate the possibility of using bio-impedance spectrometry to measure tumour and tissue response to radiation therapy. Bio -impedance measurements performed with CythorLab™ equipped with a signal generator with a known high output impedance and signal measuring device able to measure the voltage applied by the generator. The control unit triggers the signal generator that generates an MLS-sequence. The same control unit process the signal that simultaneously measured by the voltage-recording device. An FFT analysis performed to obtain the magnitude of the real and imaginary parts of the impedance spectrum. The effect of various numbers of fractions of radiation therapy (RT) on the impedance measured with surface plate electrodes investigated in male rats of the Fischer-344 strain with rat glioma N32 tumours implanted subcutaneously on the flank. Tumours produced by injecting 100 000 N32 tumour cells just below the skin. Tumours were treated about four weeks after injection when a solid tumour has developed with a diameter of 1-1.5 cm. Before treating the tumours, animals anaesthetised, and the fur over the tumour shaven and carefully to ensure good electrical contact between electrodes and skin. The electrical impedance dispersion of tissue modelled with an RC-equivalent circuit from which collective impedance parameters corresponding the cell membranes, Rm Cm intra -cellular resistance, Ri, and extra-cellular resistance R0.Impedance measurements performed over a tumour before irradiation to 5 Gy and every minute after the irradiation up to 8 minutes. A slight increase of impedance, and with a time constant of 10 minutes. The growth might be due to dry skin after irradiation or a decrease of tumour vascularity during the treatment. The capacitance of the cell membrane related to the characteristic frequency fc does not change significantly before and after radiation exposure. A special parameter, the "Loss Change Index" (LCI) which defined to vary between zero if there is no change in the phase angle and one if the phase angle after exposure approach zero. LCI reach an extreme at the characteristic frequency. The LCI value recorded at the characteristic frequency fc varied with the accumulated absorbed dose and fitted to a sigmoidal dose/response relationship

First observations of beam losses due to bound-free pair production in a heavy-ion collider

We report the first observations of beam losses due to bound-free pair production at the interaction point of a heavy-ion collider. This process is expected to be a major luminosity limit for the Large Hadron Collider (LHC) when it operates with 208Pb82+ ions because the localized energy deposition by the lost ions may quench superconducting magnet coils. Measurements were performed at the Relativistic Heavy Ion Collider (RHIC) during operation with 100 GeV/nucleon 63Cu29+ ions. At RHIC, the rate, energy and magnetic field are low enough so that magnet quenching is not an issue. The hadronic showers produced when the single-electron ions struck the RHIC beampipe were observed using an array of photodiodes. The measurement confirms the order of magnitude of the theoretical cross section previously calculated by others.Comment: 4 pages, 5 figures. Added journal ref. Corrected typos. Fixed fig 1. Minor improvements to fig. 1,3,4. Rephrased a small number of sentences (p1,3,4). Added numerical values of the aperture and the displacement for Au (p 2). Changed reference 5, added name in acknowledgments (p 4

Beam losses from ultra-peripheral nuclear collisions between Pb ions in the Large Hadron Collider and their alleviation

Electromagnetic interactions between colliding heavy ions at the Large Hadron Collider (LHC) at CERN will give rise to localized beam losses that may quench superconducting magnets, apart from contributing significantly to the luminosity decay. To quantify their impact on the operation of the collider, we have used a three-step simulation approach, which consists of optical tracking, a Monte-Carlo shower simulation and a thermal network model of the heat flow inside a magnet. We present simulation results for the case of Pb ion operation in the LHC, with focus on the ALICE interaction region, and show that the expected heat load during nominal Pb operation is 40% above the quench level. This limits the maximum achievable luminosity. Furthermore, we discuss methods of monitoring the losses and possible ways to alleviate their effect.Comment: 17 pages, 20 figure

Immunization with syngeneic interferon-gamma (IFN-g) secreting tumour cells enhance the Therapeutic effect and Abscopal effect from combined treatment of subcutaneously implanted contra-lateral N29 tumours on Fischer rats with Pulsed electric fields (PEF) and 60Co-gamma radiation.

The aim of the present study is to study the Abscopal regression of subcutaneously implanted N29 rat glioma after immunization with syngeneic IFNg secreting cells and treatment of contra-lateral tumours with pulsed electric fields (PEF) and/or radiation therapy (RT). The study was performed on rats of the Fischer-344 strain with rat glioma N29 tumours implanted subcutaneously on the flank or on both the right treated hind leg and the left untreated hind leg. Once weekly for three weeks, the animals were given intra-peritoneal injections of irradiated, modified N29 tumour cells, secreting interferon-gamma (IFN-g). PEF was given with 16 exponentially decaying pulses at a maximum electric fields strength of 1400 V/cm and t1/e= 1 ms. RT was given with 60Co gamma radiation at daily fractions of 5 Gy, to a total absorbed dose of 20 Gy. The animals were arranged into controls and groups of various treatments: PEF, RT, PEF+RT and immunization (IFNg). Fitting the data obtained from consecutive measurements of tumour volume (TV) of each individual tumour to an exponential model TV = TV0*exp[TGR*t] estimated the tumours growth rate (TGR %per day) after the day of treatment (t = 0). TGR of the right-lateral treated tumour was significantly decreased for independent treatments with PEF and RT and with the combined treatment PEF+RT. With immunization (IFNg) alone and in combination with PEF there was, however, no significant decrease of the TGR of the right-lateral tumours. But in the combination of immunization with RT or PEF+RT there was a highly significant decrease of the TGR values. The Abscopal effect was evaluated by comparing the growth rate of the untreated contra lateral tumours with the treated tumours. TGR of the left-lateral untreated tumour in the groups with independent treatment of right-lateral tumours with PEF, was not significantly reduced. But the TGR values are significantly reduced in the group of rats treated with RT and the combination PEF + RT. With IFNg alone and in combinations with PEF or RT there was no significant decrease of the TGR in the left lateral tumours. But in the combination of IFNg with PEF+RT there was a highly significant decrease of the TGR values in the left lateral tumours. The specific therapeutic effect (STE = 1 - TGRExposed/ TGRCtrl ) after treatments with PEF was 0.30±0.01 and after RT 0.46±0.04 and after the combination PEF+RT 0.36+/- 0.08. After immunization with IFNg secreting tumour cells the STE 0.09+/- 0.07 is not significantly different from zero. Also for the combination of immunization and PEF the STE value of 0.07+/- 0.07 is not significantly different from zero. In the combination of immunization with RT the STE value was 0.32+/- 0.01 that is significantly different from zero and only slightly lower than for RT alone. The STE of the combination of immunization with (PEF+RT) resulted in an unexpectedly high STE value of 0.70+/- 0.08 that is highly significantly different from zero (p < 0.0001). The specific Abscopal effect (SAE = 1 - TGRUn-Exposed/ TGRCtrl ) of the contra lateral unexposed tumours in rats treated with PEF or RT are both significantly different from zero. For RT the average SAE value is 0.33+/- 0.04 and for PEF it is 0.11+/- 0.05. The SAE value for the combined treatment with PEF + RT is 0.26+/- 0.02 that is about the same as for RT alone. For immunization with IFNg secreting tumour cells only and IFNg +PEF the SAE values were not significantly different from zero. But IFNg combined with RT result in a SAE value of 0.18±0.12 and the combination of IFNg with PEF+RT results in an improved abscopal effect with the SAE value of 0.33+/- 0.06. After combined treatment with PEF + RT the average of the therapeutic enhancement ratio (TER = STEExperimental / STEIndependent) is 0.47 +/- 0.12 and the abscopal enhancement ratio (AER = SAEExperimental / SAEIndependent) is 0.61 +/- 0.1 respectively. With all three treatment modalities combined IFNg + PEF + RT and all combinations of independent treatments with PEF, RT or IFNg are considered, the average of the TER is 1.20+/- 0.15 and AER is 1.22+/- 0.20. This might indicate that there is a synergism on the tumours on both sides by combining PEF, RT and immunization with IFNg secreting cells. These results were first presented Nov 21-24, 2002, as Poster at Society of Neuro-Oncology (SNO) Annual Meeting, San Diego, USA (Persson et al 2002)

Measurement of electromagnetic cross sections in heavy ion interactions and its consequences for luminosity lifetimes in ion colliders

The limitation of the luminosity lifetime in high energy heavy ion colliders like RHIC or LHC operating in ion mode is set by the very large cross section of beam - beam interactions. One of the dominant processes at relativistic energies is electron capture from pair production in the strong electromagnetic field provided by the high Z of the ions. The capture cross sections for Pb82+ interacting with a number of light and heavy solid targets have been measured using one of the high energy resolution 158 GeV/nucleon beams at CERN. Gas targets Ar, Kr and Xe have also been used. The results, together with results on electromagnetic dissociation, are discussed in terms of beam lifetimes for RHIC and LHC using extrapolations of the measurements to the corresponding collider energies