Design and realisation of tissue-equivalent dielectric simulators for dosimetric studies on microwave antennas for interstitial ablation.

Thermal ablation therapies, based on electromagnetic field sources (interstitial or intracavitary antennas) at radio and microwave frequencies, are increasingly used in medicine due to their proven efficacy in the treatment of many diseases (tumours, stenosis, etc). Such techniques need standardized procedures, still not completely consolidated, as to analyze the behaviour of antennas for treatment optimisation. Several tissue-equivalent dielectric simulators (also named phantoms) have been developed to represent human head tissues, and extensively used in the analysis of human exposure to the electromagnetic emissions from hand-held devices; yet, very few studies have considered other tissues, as those met in ablation therapies. The objective of this study was to develop phantoms of liver and kidney tissue to experimentally characterise interstitial microwave antennas in reference conditions. Phantom properties depend on the simulated target tissue (liver or kidney) and the considered frequency (2.45 GHz in this work), addressing the need for a transparent liquid to easily control the positioning of the probe with respect to the antenna under test. An experimental set-up was also developed and used to characterise microwave ablation antenna performances. Finally, a comparison between measurements and numerical simulations was performed for the cross-validation of the experimental set-up and the numerical model. The obtained results highlight the fundamental role played by dielectric simulators in the development of microwave ablation devices, representing the first step towards the definition of a procedure for the ablation treatment planning.

Dosimetry of a set-up for the exposure of newborn mice to 2.45-GHZ WiFi frequencies.

This work describes the dosimetry of a two waveguide cell system designed to expose newborn mice to electromagnetic fields associated with wireless fidelity signals in the frequency band of 2.45 GHz. The dosimetric characterisation of the exposure system was performed both numerically and experimentally. Specific measures were adopted with regard to the increase in both weight and size of the biological target during the exposure period. The specific absorption rate (SAR, W kg(-1)) for 1 W of input power vs. weight curve was assessed. The curve evidenced an SAR pattern varying from <1 W kg(-1) to >6 W kg(-1) during the first 5 weeks of the life of mice, with a peak resonance phenomenon at a weight around 5 g. This curve was used to set the appropriate level of input power during experimental sessions to expose the growing mice to a defined and constant dose.

Effects of exposure of newborn patched1 heterozygous mice to GSM, 900 MHz.

Patched1 heterozygous knockout mice (Ptc1+/-), an animal model of multiorgan tumorigenesis in which ionizing radiation dramatically accelerates tumor development, were used to study the potential tumorigenic effects of electromagnetic fields (EMFs) on neonatal mice. Two hundred Ptc1+/- mice and their wild-type siblings were enrolled in this study. Newborn mice were exposed to 900 MHz radiofrequency radiation (average SAR: 0.4 W/kg for 5 days, 0.5 h twice a day) or were sham exposed. We found that RF EMFs simulating the Global System for Mobile Communications (GSM) did not affect the survival of the mice, because no statistically significant differences in survival were found between exposed and sham-exposed animals. Also, no effects attributable to radiofrequency radiation were observed on the incidence and histology of Ptc1-associated cerebellar tumors. Moreover, the skin phenotype was analyzed to look for proliferative effects of RF EMFs on the epidermal basal layer and for acceleration of preneoplastic lesions typical of the basal cell carcinoma phenotype of this model. We found no evidence of proliferative or promotional effects in the skin from neonatal exposure to radiofrequency radiation. Furthermore, no difference in Ptc1-associated rhabdomyosarcomas was detected between sham-exposed and exposed mice. Thus, under the experimental conditions tested, there was no evidence of life shortening or tumorigenic effects of neonatal exposure to GSM RF radiation in a highly tumor-susceptible mouse model.

Exposure setup to study potential adverse effects at GSM 1800 and UMTS frequencies on the auditory systems of rats.

To investigate possible biological effects of exposure to electromagnetic (EM) fields at the frequencies of global system for mobile communication (GSM) 1800 system and universal mobile telecommunication system (UMTS) on the auditory system of rats, an exposure setup for in vivo experiments is presented. The study was carried out in the framework of two European research projects. The target of the investigation was the cochlea. A dosimetric study was performed, both numerically and through direct measurements, to assess the interaction of the radiated fields and the dose distribution in the biological target. For the local exposure of rats, a loop antenna operating at the frequency bands of interest was designed, realised and characterised through numerical and experimental dosimetric procedures. Moreover, an exposure apparatus was set up, consisting of three arrays of four loop antennas, placed on three levels, thus allowing simultaneous exposure of 12 rats to give statistical power to the experiments. To isolate the exposure arrays, the setup was assembled by a wooden rack with EM field absorbing panels, inserted among the levels and at the four sides of the rack. Isolation was verified by direct measurements. Two exposure arrays were simultaneously supplied, whereas the third one was used for sham exposure. Blind exposure was achieved through a black box, hiding physical connections to the microwave power supply. During exposure sessions, rats were restrained in special plastic jigs for repeatable positioning, thus assuring the fixed level of dose in the target.

Proliferation and apoptosis in a neuroblastoma cell line exposed to 900 MHz modulated radiofrequency field.

The aim of this study was to examine whether a modulated radiofrequency of the type used in cellular phone communications at a specific absorption rate (SAR) higher than International Commission on Non-ionizing Radiation Protection (ICNIRP) reference level for occupational exposure, could elicit alterations on proliferation, differentiation, and apoptosis processes in a neuroblastoma cell line. The cell line was exposed for 24, 48, and 72 h to 900 MHz radiofrequency and proliferation and differentiation were tested by WST-I assay and by a molecular analysis of specific markers, two oncogenes and a cytoskeleton protein, in exponential growth phase and in synchronized cell cultures. Apoptosis was evaluated by caspase activation analysis and by molecular detection of Poly (ADP-ribose) polimerase (PARP) cleavage. Combined exposures to radiofrequency and to the differentiative agent retinoic acid or to the apoptotic inducer camptothecin were carried out to test possible interference between electromagnetic field and chemical agents. Overall our data suggest that 900 MHz radiofrequency exposure up to 72 h does not induce significant alterations in the three principal cell activities in a neuroblastoma cell line.

Evaluation of genotoxic effect of low level 50 Hz magnetic fields on human blood cells using different cytogenetic assays.

The question whether extremely low frequency magnetic fields (ELFMFs) may contribute to mutagenesis or carcinogenesis is of current interest. In order to evaluate the possible genotoxic effects of ELFMFs, human blood cells from four donors were exposed in vitro for 48 h to 50 Hz, 1 mT uniform magnetic field generated by a Helmholtz coil system. Comet assay (SCGE), sister chromatid exchanges (SCE), chromosome aberrations (CAs), and micronucleus (MN) test were used to assess the DNA damage. ELF pretreated cells were also irradiated with 1 Gy of X-ray to investigate the possible combined effect of ELFMFs and ionizing radiation. Furthermore, nuclear division index (NDI) and proliferation index (PRI) were evaluated. Results do not evidence any DNA damage induced by ELFMF exposure or any effect on cell proliferation. Data obtained from the combined exposure to ELFMFs and ionizing radiation do not suggest any synergistic or antagonistic effect.

1800 MHz in vitro exposure device for experimental studies on the effects of mobile communication systems.

A wire patch cell (WPC) operating at the uplink frequency band of GSM 1800 MHz has been designed for in vitro experiments with the aim of investigating the possible biological effects of electromagnetic radiation associated with cellular phones. The 1800 MHz WPC design is a direct descendant of the original 900 MHz WPC introduced by Laval et al. This system provides a homogeneous specific absorption rate distribution, using four 3.5 cm petri dishes simultaneously. Numerical dosimetry has been performed using a commercial code (CST Microwave Studio), in order to evaluate accurately the efficiency of the structure (in terms of W kg(-1) per 1 W input power) and the distribution in the chosen biological target. The numerical results have been confirmed by experimental measurements performed by measuring thermal increase due to a high power impulse. The efficiency of the structure is 1.25 +/- 25% W kg(-1) per 1 W input power higher than the efficiency of the 900 MHz WPC. A few adjustments have been made in order to use the WPC in a standard incubator and to avoid thermal increases related to the radio frequency exposure. This exposure system has been adopted for the experiments scheduled in the RAMP and GUARD projects (VFPE).

Absence of genotoxicity in human blood cells exposed to 50 Hz magnetic fields as assessed by comet assay, chromosome aberration, micronucleus, and sister chromatid exchange analyses.

In the past, epidemiological studies indicated a possible correlation between the exposure to ELF fields and cancer. Public concern over possible hazards associated with exposure to extremely low frequency magnetic fields (ELFMFs) stimulated an increased scientific research effort. More recent research and laboratory studies, however, have not been able to definitively confirm the correlation suggested by epidemiological studies. The aim of this study was to evaluate the effects of 50 Hz magnetic fields in human blood cells exposed in vitro, using several methodological approaches for the detection of genotoxicity. Whole blood samples obtained from five donors were exposed for 2 h to 50 Hz, 1 mT uniform magnetic field generated by a Helmholtz coil system. Comet assay, sister chromatid exchanges (SCE), chromosome aberrations (CA), and micronucleus (MN) tests were used to assess DNA damage, one hallmark of malignant cell transformation. The effects of a combined exposure with X-rays were also evaluated. Results obtained do not show any significant difference between ELFMFs exposed and unexposed samples. Moreover, no synergistic effect with ionizing radiation has been observed. A slight but significant decrease of cell proliferation was evident in ELFMFs treated samples and samples subjected to the combined exposure.

Effects of 50 Hz electromagnetic field exposure on apoptosis and differentiation in a neuroblastoma cell line.

Experiments were carried out to assess whether a magnetic field of 50 Hz and 1 mT can influence apoptosis and proliferation in the human neuroblastoma cell line LAN-5. TUNEL assays and poly-ADP ribose polymerase (PARP) expression analysis were performed to test apoptosis induction, and the WST-1 assay was used to calculate the proliferation index in a long term exposure. No alterations were found in cellular ability to undergo programmed cell death, but a small increase in the proliferation index was evidenced after 7 days of continuous exposure. Also, a slight and transient increase of B-myb oncogene expression was detected after 5 days of exposure. Combined exposures of cells to EMF and to chemical agents which interfere with proliferation, such as the differentiative agent retinoic acid and the apoptotic inducer camptothecin, showed an antagonistic effect of magnetic fields against the differentiation of the LAN-5 cells and a protective effect towards apoptosis.

Dosimetric techniques for the evaluation of the em power absorption induced by cellular phones.

International guidelines. ICNIRP, and proposed standards. IEEE-ANSI, define basic restrictions in terms of rate of power absorbed for mass unit (SAR) for localised exposure of electromagnetic fields such as in the near field region of cellular phones. Compliance tests of cellular phones consist in checking that emitted power from mobile telecommunication equipment (MTE) is below the reference levels and they are performed by assessing the absorbed power in specific head phantoms. The outcome of this work is the description of experimental procedures for evaluating SAR induced into the head by localised exposure. The set up instituted for compliance testing of MTE is described with the different components: dielectric simulators, electric field sensors. scanning system, remote control and data recording. Calibration procedures of E sensors and uncertainty evaluation of measures are presented. Finally the results of a comparison among a few European laboratories and of a test of some hand-set devices are shown.

Effects of microwaves (900 MHz) on the cochlear receptor: exposure systems and preliminary results.

The purpose of this paper is to present the experimental device and the work in progress performed in search for objective organic correlation of damage to hearing, examining possible acoustic otofunctional effects on the cochlear epithelium of the rat due to exposure to microwaves (900 MHz). Two experiments using male Sprague-Dawley rats were carried out with a far-field exposure in a cubic chamber. No statistically significant evidence was obtained at both specific absorption rate (SAR) values. The exposure system and the diagnostic apparatus are extremely useful to investigate a potential effect on the auditory system: however, with the parameters applied in these experiments, no evidence was observed.

SAR optimization in a phased array radiofrequency hyperthermia system. Specific absorption rate.

RF deep hyperthermia systems make use of phased arrays of applicators in order to heat tumors selectively while maintaining healthy tissue at normal temperatures. A new method for the array synthesis is proposed based on the identification of targets to be heated (tumors) and targets to be prevented from excess electromagnetic radiation. The best array feed for each target is found from the solution of the eigenvector problem for a positive definite Hermitian matrix defined for that target. The optimal feed in a global sense then results from a trade-off of the best feeds of individual targets enforced through minimization of an objective function aimed at weighting the distances of the globally optimal feed from the feed vectors optimized for each target separately. An application to the heating of a pelvis is provided as an example.

Practical experience in electromagnetic hyperthermia quality control procedures within the context of international guidelines.

Recent international guidelines on hyperthermia (HT) quality assurance have pointed out the necessity of defining standard operative procedures and technical checks to guarantee an accurate performance of HT treatments. In the present paper, experience is described of quality control procedures that are performed in agreement with the more general guidelines concerning thermometry, sensor positioning, phantoms, applicator characterisation, and electromagnetic (EM) radiation leakage. This practical experience comes from the use of equipment for superficial and loco-regional HT working in the range 13.56-915 MHz.

Radiotherapy and hyperthermia. Analysis of clinical results and identification of prognostic variables.

Site- and tumor-specific data obtained from two groups of patients with head and neck and melanoma lesions, respectively, showed that both immediate response and response duration were enhanced by the addition of heat. Two important variables, however, such as tumor volume and "isoeffect thermal dose" appeared to influence local tumor control. The volume effect was less pronounced in the lesions treated with radiotherapy plus heat than in those treated with radiotherapy alone, suggesting that the addition of heat was more damaging to the large than to the small lesions. Furthermore, a striking isoeffect thermal dose-response relationship was shown in head and neck lesions. Those data were collected and used to design a mathematical model relating the probability of local control to clinical and treatment variables. The analysis shows that, by using the same radiation parameters, the probability of local tumor control is a function of both "isoeffect thermal dose" and tumor volume.

Problem of sequence and fractionation in the clinical application of combined heat and radiation.

Tumor control, thermal enhancement, and therapeutic effect have been evaluated in a series of studies on 77 patients with a total of 163 multiple superficial lesions by using different protocols of combined radiotherapy and local external hyperthermia. Local tumor control and recurrence rate were constantly better in lesions treated with combined treatment in comparison with those treated with radiotherapy alone, regardless of treatment schedule. The enhancement of tumor control appeared to be related to both the magnitude of the applied heat and the size of radiation fractions, in that an increase in either produced an increase in tumor control. When tumor and critical normal tissue were heated to the same temperature, the immediate combination of heat and large radiation fractions resulted in a pronounced enhancement of tumor control, but the concomitantly heated normal tissue showed an increased percentage of radiation reaction, resulting in a low therapeutic advantage. By introducing an interval of 4 hr between the two modalities or by delivering few heat fractions during the course of a conventional fractionation radiotherapy, the enhancement of tumor control was lower, but the increase in skin reaction was minimal, resulting in a clearly improved therapeutic effect. When the tumor could be preferentially heated with respect to normal tissue, the immediate combination of the highest hyperthermic treatment and the largest radiation fractions resulted in the best therapeutic advantage, since no increase of skin reaction was observed.