http://repub.eur.nl/res/aut/13324/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39555/ 2013-03-01T00:00:00Z Background: Sepsis and subsequent multiple-organ failure are the predominant causes of late mortality in trauma patients. Susceptibility and response to infection is, in part, heritable. Single-nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) and cluster of differentiation 14 (CD14) genes of innate immunity may play a key role. The aim of this study was to assess if SNPs in TLR/CD14 predisposed trauma patients to infection. Methods: A prospective cohort of trauma patients (age 18-80 years; injury severity score [ISS] ≥ 16) admitted to a Level I trauma center between January 2008 and April 2011 was genotyped for SNPs in TLR2 (T-16934A and R753Q), TLR4 (D299G and T399I), TLR9 (T-1486C and T-1237C), and CD14 (C-159T) using high-resolution melting analysis. Association of genotype with prevalence of positive culture findings (gram positive, gram negative, fungi), systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and mortality was tested with χ2and logistic regression analysis. Results: Genotyping was performed for 219 patients, of whom 51% developed positive culture findings in sputum, wounds, blood, or urine. SIRS developed in 64%, sepsis in 36%, and septic shock in 17%. The TLR2 T-16934A TA genotype increased the risk of a gram-positive infection (odds ratio, 2.816; 95% confidence interval, 1.249-6.348; p = 0.013) and SIRS (odds ratio, 2.386; 95% confidence interval, 1.011-5.632; p = 0.047). Trends were noted for TLR9 and CD14 SNPs but did not reach statistical significance. Sepsis and septic shock were unrelated to any of the SNPs studied. Conclusion: Aberrant functioning of the TLR/CD14 pathway of innate immunity changes the risk of infectious complications in severely injured trauma patients. Of the seven SNPs studied, the TLR2 T-16934A increased the risk, the TLR9 T-1486C SNPs may decrease the risk, and TLR4 variation seemed unrelated to outcome. Early genotyping may prove to be helpful in the future in identifying polytraumatized patients at risk for infectious outcome. Copyright http://repub.eur.nl/res/pub/37499/ 2012-10-26T00:00:00Z Electromagnetic fields (EMF) are present everywhere in our environment but are usually invisible to the human eye. EMF for example generated by mobile phones and 50Hz power lines, can cause electric fields, currents and tissue heating in the human body. In the past, exposure limits were developed to avoid adverse health effects. These limits were derived from dose assessments using simple models which for example approximate the human by homogeneous spheroids. Nowadays, state-of-the-art electromagnetic models enable to predict and visualize the propagation of electromagnetic waves in the human anatomy. These models can provide detailed information on the exposure of the general public in daily life situations and those of patients and staff in medical applications such as hyperthermia treatments of cancer and Magnetic Resonance Imaging (MRI). In this thesis, a comprehensive assessment of the exposure to different EMF sources is provided for both children and adults. An evaluation is made how the guidelines, based on simple models, translate to the dose in complex anatomies in various population groups. Further, it is demonstrated that validated electromagnetic models can be used for the benefit of medical applications, by providing the medical staff a clear picture of the actual applied dose in patients and by efficient virtual prototyping of improved medical devices. http://repub.eur.nl/res/pub/20697/ 2010-04-06T00:00:00Z To apply high-quality hyperthermia treatment to tumours at deep locations in the head and neck (H&N), we have designed and built a site-specific phased-array applicator. Earlier, we demonstrated its features in parameter studies, validated those by phantom measurements and clinically introduced the system. In this paper we will critically reviewour first clinical experiences and demonstrate the pivotal role of hyperthermia treatment planning (HTP). Three representative patient cases (thyroid, oropharynx and nasal cavity) are selected and discussed. Treatment planning, the treatment, interstitially measured temperatures and their interrelation are analysed from a physics point of view. Treatments lasting 1 h were feasible and well tolerated and no acute treatment-related toxicity has been observed. Maximum temperatures measured are in the range of those obtained during deep hyperthermia treatments in the pelvic region but mean temperatures are still to be improved. Further, we found that simulated power absorption correlated well with measured temperatures illustrating the validity of our treatment approach of using energy profile optimizations to arrive at higher temperatures. This is the first data proving that focussed heating of tumours in the H&N is feasible. Further, HTP proved a valuable tool in treatment optimization. Items to improve are (1) the transfer of HTP settings into the clinic and (2) the registration of the thermal dose, i.e. dosimetry. http://repub.eur.nl/res/pub/19239/ 2010-02-26T00:00:00Z Purpose: For our head-and-neck hyperthermia (HT) applicator, an amplifier system with full amplitude and phase-control to deliver the radio-frequency signals, was not available. We therefore designed and tested a 433.92 MHz multi-channel amplifier system. System description: The design consists of a direct digital synthesizer (DDS) system that generates 12 phase-controlled coherent 433.92 MHz signals, which are amplified to maximum 200 W output per channel. Directional couplers are placed at the amplifiers to couple a small portion of both forward and reflected signals to gain-and-phase detectors. The power setting is applied with a resolution of 2 W and for the phase it is 0.1°. The channels are sequentially sampled at 100 Hz per channel. Methods: We tested the performance of the designed amplifier system by measuring the RF spectrum, power and phase accuracy, and by characterising the feedback control by using highly accurate power and phase meters. Results: The spurious emission is less than 60 dBc and the first two harmonic frequencies are suppressed more than 45 dB. The measurement accuracy for the power (±5%) is valid for at least 20 days after calibration and for the phase (±5%°) it is valid for at least 2 months. Conclusions: The amplifier system operates according to our design criteria to support targeted HT. It can be used for both our in-house developed superficial and head-and-neck HT applicators or any other HT applicator that works on the same frequency of 433.92 MHz. http://repub.eur.nl/res/pub/20698/ 2010-01-01T00:00:00Z To apply high-quality hyperthermia treatment to tumours at deep locations in the head and neck (H&N), we have designed and built a site-specific phased-array applicator. Earlier, we demonstrated its features in parameter studies, validated those by phantom measurements and clinically introduced the system. In this paper we will critically reviewour first clinical experiences and demonstrate the pivotal role of hyperthermia treatment planning (HTP). Three representative patient cases (thyroid, oropharynx and nasal cavity) are selected and discussed. Treatment planning, the treatment, interstitially measured temperatures and their interrelation are analysed from a physics point of view. Treatments lasting 1 h were feasible and well tolerated and no acute treatment-related toxicity has been observed. Maximum temperatures measured are in the range of those obtained during deep hyperthermia treatments in the pelvic region but mean temperatures are still to be improved. Further, we found that simulated power absorption correlated well with measured temperatures illustrating the validity of our treatment approach of using energy profile optimizations to arrive at higher temperatures. This is the first data proving that focussed heating of tumours in the H&N is feasible. Further, HTP proved a valuable tool in treatment optimization. Items to improve are (1) the transfer of HTP settings into the clinic and (2) the registration of the thermal dose, i.e. dosimetry. http://repub.eur.nl/res/pub/20652/ 2007-11-01T00:00:00Z In this paper, we describe a specifically designed patch antenna that can be used as the basis antenna element of a clinical phased-array head and neck hyperthermia applicator. Using electromagnetic simulations we optimized the dimensions of a probe-fed patch antenna design for operation at 433 MHz. By several optimization steps we could converge to a theoretical reflection of -38 dB and a bandwidth (-15 dB) of 20 MHz (4.6%). Theoretically, the electrical performance of the antenna was satisfactory over a temperature range of 15 C–35 C, and stable for patient-antenna distances to as low as 4 cm. In an experimental cylindrical setup using six elements of the final patch design, we measured the impedance characteristics of the antenna 1) to establish its performance in the applicator and 2) to validate the simulations. For this experimental setup we simulated and measured comparable values: -21 dB reflection at 433 MHz and a bandwidth of 18.5 MHz. On the basis of this study, we anticipate good central interference of the fields of multiple antennas and conclude that this patch antenna design is very suitable for the clinical antenna array. In future research we will verify the electrical performance in a prototype applicator. http://repub.eur.nl/res/pub/20653/ 2007-11-01T00:00:00Z The purpose of this work was to define all features, and show the potential, of the novel HYPERcollar applicator system for hyperthermia treatments in the head and neck region. The HYPERcollar applicator consists of (1) an antenna ring, (2) a waterbolus system and (3) a positioning system. The specific absorption rate (SAR) profile of this applicator was investigated by performing infra-red measurements in a cylindrical phantom. Mandatory patient-specific treatment planning was performed as an object lesson to a patient with a laryngeal tumour and an artificial lymph node metastasis. Comfort tests with healthy volunteers have revealed that the applicator provides sufficient comfort to maintain in treatment position for an hour: the standard hyperthermia treatment duration in our centre. By phantom measurements, we established that a central focus in the neck can be obtained, with 50% iso-SAR lengths of 3.5 cm in transversal directions (x/y) and 9–11 cm in the axial direction (z). Using treatment planning by detailed electromagnetic simulations, we showed that the SAR pattern can be optimised to enable simultaneous encompassing of a primary laryngeal tumour and a lymph node metastasis at the 25% iso-SAR level. This study shows that the applicator enables a good control, and sufficient possibilities for optimisation, of the SAR pattern. In an ongoing clinical feasibility study, we will investigate the possibilities of heating various target regions in the neck with this apparatus. http://repub.eur.nl/res/pub/20654/ 2007-05-01T00:00:00Z Abstract Purpose: Definition of all features and the potential of the novel HYPERcollar applicator system for hyperthermia treatments in the head and neck (H&N) region. Methods and Materials: The HYPERcollar applicator consists of 1) an antenna ring, 2) a waterbolus system and 3) a positioning system. The specific absorption rate (SAR) profile of this applicator is investigated by performing infra-red (IR) measurements in a cylindrical phantom. Mandatory patient-specific treatment planning is performed as an object lesson to a patient with a laryngeal tumour and an artificial lymph node metastasis. Results: The comfort tests with healthy volunteers have revealed that the applicator provides su±cient comfort to maintain in treatment position for an hour: in our center the standard hyperthermia treatment duration. We further established that a central focus in the neck can be obtained, with 50% iso-SAR lengths of 3.5cm in transversal directions and 9-11cm in the axial direction (z). Using treatment planning by detailed electromagnetic simulations, we showed that the SAR pattern can be optimized to enable simultaneous encompassing a primary laryngeal tumour and a lymph node metastasis at the 25% iso-SAR level. Conclusions: A site-specific H&N applicator was designed that enables good control and sufficient possibilities for optimizing the SAR pattern. In an ongoing clinical feasibility study we will investigate the possibilities of heating various target regions in the neck with this apparatus. http://repub.eur.nl/res/pub/10493/ 2007-02-01T00:00:00Z Purpose: To experimentally verify the feasibility of focused heating in the neck region by an array of two rings of six electromagnetic antennas. We also measured the dynamic specific absorption rate (SAR) steering possibilities of this setup and compared these SAR patterns to simulations. Methods and Materials: Using a specially constructed laboratory prototype head-and-neck applicator, including a neck-mimicking cylindrical muscle phantom, we performed SAR measurements by electric field, Schottkydiode sheet measurements and, using the power-pulse technique, by fiberoptic thermometry and infrared thermography. Using phase steering, we also steered the SAR distribution in radial and axial directions. All measured distributions were compared with the predictions by a finite-difference time-domain–based electromagnetic simulator. Results: A central 50% iso-SAR focus of 35 +/- 3 mm in diameter and about 100 +/- 15 mm in length was obtained for all investigated settings. Furthermore, this SAR focus could be steered toward the desired location in the radial and axial directions with an accuracy of ~5 mm. The SAR distributions as measured by all three experimental methods were well predicted by the simulations. Conclusion: The results of our study have shown that focused heating in the neck is feasible and that this focus can be effectively steered in the radial and axial directions. For quality assurance measurements, we believe that the Schottky-diode sheet provides the best compromise among effort, speed, and accuracy, although a more specific and improved design is warranted. http://repub.eur.nl/res/pub/10494/ 2007-02-01T00:00:00Z Purpose: Investigation into the feasibility of a circular array of dipole antennas to deposit RF-energy centrally in the neck as a function of: (1) patient positioning, (2) antenna ring radius, (3) number of antenna rings, (4) number of antennas per ring and (5) distance between antenna rings. Materials and Methods: Power absorption (PA) distributions in realistic, head and neck, anatomy models are calculated at 433 MHz. Relative PA distributions corresponding to different set-ups were analysed using the ratio of the average PA (aPA) in the target and neck region. Results: Enlarging the antenna ring radius from 12.5cm to 25 cm resulted in a ~21% decrease in aPA. By changing the orientation of the patients with respect to the array an increase by ~11% was obtained. Increase of the amount of antenna rings led to a better focussing of the power (1 - 2 / 3: ~17%). Increase of the distance between the antenna rings resulted in a smaller (more target region conformal) focus but also a decreased power penetration. Conclusions: A single optimum array setup suitable for all patients is difficult to define. Based on the results and practical limitations a setup consisting of two rings of six antennas with a radius of 20 cm and 6 cm array spacing is considered a good choice providing the ability to heat the majority of patients.