Integrated thermal and magnetic susceptibility modeling for air-motion artifact correction in proton resonance frequency shift thermometry.

PURPOSE: Hyperthermia treatments are successful adjuvants to conventional cancer therapies in which the tumor is sensitized by heating. To monitor and guide the hyperthermia treatment, measuring the tumor and healthy tissue temperature is important. The typical clinical practice heavily relies on intraluminal probe measurements that are uncomfortable for the patient and only provide spatially sparse temperature information. A solution may be offered through recent advances in magnetic resonance thermometry, which allows for three-dimensional internal temperature measurements. However, these measurements are not widely used in the pelvic region due to a low signal-to-noise ratio and presence of image artifacts. METHODS: To advance the clinical integration of magnetic resonance-guided cancer treatments, we consider the problem of removing air-motion-induced image artifacts. Thereto, we propose a new combined thermal and magnetic susceptibility model-based temperature estimation scheme that uses temperature estimates to improve the removal of air-motion-induced image artifacts. The method is experimentally validated using a dedicated phantom that enables the controlled injection of air-motion artifacts and with in vivo thermometry from a clinical hyperthermia treatment. RESULTS: We showed, using probe measurements in a heated phantom, that our method reduced the mean absolute error (MAE) by 58% compared to the state-of-the-art near a moving air volume. Moreover, with in vivo thermometry our method obtained a MAE reduction between 17% and 95% compared to the state-of-the-art. CONCLUSION: We expect that the combined thermal and magnetic susceptibility modeling used in model-based temperature estimation can significantly improve the monitoring in hyperthermia treatments and enable feedback strategies to further improve MR-guided hyperthermia cancer treatments.

Recent technological advancements in radiofrequency- andmicrowave-mediated hyperthermia for enhancing drug delivery.

Hyperthermia therapy is a potent enhancer of chemotherapy and radiotherapy. In particular, microwave (MW) and radiofrequency (RF) hyperthermia devices provide a variety of heating approaches that can treat most cancers regardless the size. This review introduces the physics of MW/RF hyperthermia, the current state-of-the-art systems for both localized and regional heating, and recent advancements in hyperthermia treatment guidance using real-time computational simulations and magnetic resonance thermometry. Clinical trials involving RF/MW hyperthermia as adjuvant for chemotherapy are also presented per anatomical site. These studies favor the use of adjuvant hyperthermia since it significantly improves curative and palliative clinical outcomes. The main challenge of hyperthermia is the distribution of state-of-the-art heating systems. Nevertheless, we anticipate that recent technology advances will expand the use of hyperthermia to chemotherapy centers for enhanced drug delivery. These new technologies hold great promise not only for (image-guided) perfusion modulation and sensitization for cytotoxic drugs, but also for local delivery of various compounds using thermosensitive liposomes.

The Effect of the Time Interval Between Radiation and Hyperthermia on Clinical Outcome in 400 Locally Advanced Cervical Carcinoma Patients.

Background: Addition of deep hyperthermia to radiotherapy results in improved local control (LC) and overall survival compared to radiotherapy alone in cervical carcinoma patients. Based on preclinical data, the time interval between radiotherapy, and hyperthermia is expected to influence treatment outcome. Clinical studies addressing the effect of time interval are sparse. The repercussions for clinical applications are substantial, as the time between radiotherapy and hyperthermia should be kept as short as possible. In this study, we therefore investigated the effect of the time interval between radiotherapy and hyperthermia on treatment outcome. Methods: We analyzed all primary cervical carcinoma patients treated between 1996 and 2016 with thermoradiotherapy at our institute. Data on patients, tumors and treatments were collected, including the thermal dose parameters TRISE and CEM43T90. Follow-up data on tumor status and survival as well as late toxicity were collected. Data was analyzed using Cox proportional hazards analysis and Kaplan Meier analysis. Results: 400 patients were included. Kaplan Meier and univariate Cox analysis showed no effect of the time interval (range 30-230 min) on any clinical outcome measure. Besides known prognostic factors, thermal dose parameters TRISE and CEM43T90 had a significant effect on LC. In multivariate analysis, the thermal dose parameter TRISE (HR 0.649; 95% CI 0.501-0.840) and the use of image guided brachytherapy (HR 0.432; 95% CI 0.214-0.972), but not the time interval, were significant predictors of LC and disease specific survival. Conclusions: The time interval between radiotherapy and hyperthermia, up to 4 h, has no effect on clinical outcome. These results are re-ensuring for our current practice of delivering hyperthermia within maximal 4 h after radiotherapy.

The potential of constrained SAR focusing for hyperthermia treatment planning: analysis for the head & neck region.

Clinical trials have shown that hyperthermia is a potent adjuvant to conventional cancer treatments, but the temperatures currently achieved in the clinic are still suboptimal. Hyperthermia treatment planning simulations have potential to improve the heating profile of phased-array applicators. An important open challenge is the development of an effective optimization procedure that enables uniform heating of the target region while keeping temperature below a threshold in healthy tissues. In this work, we analyzed the effectiveness and efficiency of a recently proposed optimization approach, i.e. focusing via constrained power optimization (FOCO), using 3D simulations of twelve clinical patient specific models. FOCO performance was compared against a clinically used particle swarm based optimization approach. Evaluation metrics were target coverage at the 25% iso-SAR level, target hotspot quotient, median target temperature (T50) and computational requirements. Our results show that, on average, constrained power focusing performs slightly better than the clinical benchmark ([Formula: see text]T50 [Formula: see text] °C), but outperforms this clinical benchmark for large target volumes ([Formula: see text]40 cm[Formula: see text], [Formula: see text]T50 [Formula: see text] °C). In addition, the results are achieved in a shorter time ([Formula: see text]%) and are repeatable because the approach is formulated as a convex optimization problem.

The potential of time-multiplexed steering in phased array microwave hyperthermia for head and neck cancer treatment.

Clinical studies have shown that hyperthermia sensitizes tumor cells for conventional therapies. During phased-array microwave hyperthermia, an array of antennas is used to focus the electromagnetic waves at the target region. Selective heating, while preserving the healthy tissue, is a demanding challenge and currently patient specific pre-treatment planning is used to optimize the amplitudes and phases of the waves. In addition, when needed, this single optimal heat distribution is adapted using the simulations based on the feedback from thermo-sensors and the patient. In this paper, we hypothesize that sequential, i.e. 'time-multiplexed', application of multiple Pareto optimal heating patterns provides a better time-averaged treatment quality. To test the benefit of such a time-multiplexed approach, a multi-objective genetic algorithm was introduced to balance two objectives that both focus the specific absorption rate (SAR) delivered to the target region but differ in the suppressing of pre-defined hotspots. This step leads to two Pareto optimal distributions. These 'diverse' antenna settings are then applied sequentially and thermal simulations are used to evaluate the effectiveness of the time-multiplexed steering. The proposed technique is tested using treatment planning data of a representative dataset of five head and neck patients for the HYPERcollar3D. Steering dynamics are analysed and the time-multiplexed steering is compared to the current static solution used in the clinic, i.e. hotspot-target SAR quotient optimization using particle swarm optimization. Our results demonstrate that realistic steering periods of 10s suffice to stabilize temperatures within 0.04 °C and the ability to enhance target heating while reducing hotspots, i.e. 0.3 °C-1.2 °C improvement in T 50 while reducing hotspot temperatures by 0.6 °C-1.5 °C.

Deep hyperthermia with the HYPERcollar system combined with irradiation for advanced head and neck carcinoma - a feasibility study.

PURPOSE: Radiotherapy (RT) treatment of locally-advanced and recurrent head and neck carcinoma (HNC) results in disappointing outcomes. Combination of RT with cisplatin or cetuximab improves survival but the increased toxicity and patient's comorbidity warrant the need for a less-toxic radiosensitizer. Stimulated by several randomized studies demonstrating the radio-sensitizing effect of hyperthermia, we developed the HYPERcollar. Here, we report early experience and toxicity in patients with advanced HNC. METHODS AND MATERIALS: 119 hyperthermia treatments given to 27 patients were analyzed. Hyperthermia was applied once a week by the HYPERcollar aimed at achieving 39-43 °C in the target area, up to patients' tolerance. Pre-treatment planning was used to optimize treatment settings. When possible, invasive thermometry catheters were placed. RESULTS: Mean power applied during the 119 hyperthermia treatments ranged from 120 to 1007 W (median 543 W). 15 (13%) hyperthermia treatments were not fully completed due to: pain allocated to hyperthermia (6/15), dyspnea from sticky saliva associated with irradiation (2/15) and unknown reasons (7/15). No severe complications or enhanced thermal or mucosal toxicities were observed. Excluding post-operative treatment, response rates after 3 months were 46% (complete) and 7% (partial). CONCLUSION: Hyperthermia with the HYPERcollar proved to be safe and feasible with good compliance and promising outcome.

Differential Evolution Optimization of the SAR Distribution for Head and Neck Hyperthermia.

Hyperthermia is an emerging cancer treatment modality, which involves applying heat to the malignant tumor. The heating can be delivered using electromagnetic (EM) energy, mostly in the radiofrequency (RF) or microwave range. Accurate patient-specific hyperthermia treatment planning (HTP) is essential for effective and safe treatments, in particular, for deep and loco-regional hyperthermia. An important aspect of HTP is the ability to focus microwave energy into the tumor and reduce the occurrence of hot spots in healthy tissue. This paper presents a method for optimizing the specific absorption rate (SAR) distribution for the head and neck cancer hyperthermia treatment. The SAR quantifies the rate at which localized RF or microwave energy is absorbed by the biological tissue when exposed to an EM field. A differential evolution (DE) optimization algorithm is proposed in order to improve the SAR coverage of the target region. The efficacy of the proposed algorithm is demonstrated by testing with the Erasmus MC patient dataset. DE is compared to the particle swarm optimization (PSO) method, in terms of average performance and standard deviation and across various clinical metrics, such as the hot-spot-tumor SAR quotient (HTQ), treatment quantifiers, and temperature parameters. While hot spots in the SAR distribution remain a problem with current approaches, DE enhances focusing microwave energy absorption to the target region during hyperthermia treatment. In particular, DE offers improved performance compared to the PSO algorithm currently deployed in the clinic, reporting a range of improvement of HTQ standard deviation of between 40.1-96.8% across six patients.

A printed Yagi-Uda antenna for application in magnetic resonance thermometry guided microwave hyperthermia applicators.

Biological studies and clinical trials show that addition of hyperthermia stimulates conventional cancer treatment modalities and significantly improves treatment outcome. This supra-additive stimulation can be optimized by adaptive hyperthermia to counteract strong and dynamic thermoregulation. The only clinically proven method for the 3D non-invasive temperature monitoring required is by magnetic resonance (MR) temperature imaging, but the currently available set of MR compatible hyperthermia applicators lack the degree of heat control required. In this work, we present the design and validation of a high-frequency (433 MHz ISM band) printed circuit board antenna with a very low MR-footprint. This design is ideally suited for use in a range of hyperthermia applicator configurations. Experiments emulating the clinical situation show excellent matching properties of the antenna over a 7.2% bandwidth (S 11 < -15 dB). Its strongly directional radiation properties minimize inter-element coupling for typical array configurations (S 21 < -23 dB). MR imaging distortion by the antenna was found negligible and MR temperature imaging in a homogeneous muscle phantom was highly correlated with gold-standard probe measurements (root mean square error: RMSE = 0.51 °C and R 2 = 0.99). This work paves the way for tailored MR imaging guided hyperthermia devices ranging from single antenna or incoherent antenna-arrays, to real-time adaptive hyperthermia with phased-arrays.

Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF.

The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg(-1)) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients' feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R (2) = 0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature simulations as a dosimetric measure in electromagnetic exposure risk assessments.

Local hyperthermia combined with radiotherapy and-/or chemotherapy: recent advances and promises for the future.

Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment delivery, thermal treatment planning, thermal dose monitoring through noninvasive thermometry and online adaptive temperature modulation. The review summarizes the outcomes from various clinical studies (both randomized and nonrandomized) where hyperthermia is used as a thermal sensitizer of radiotherapy and-/or chemotherapy in various solid tumors and presents an overview of the progresses in loco-regional hyperthermia. These recent developments, supported by positive clinical outcomes should merit hyperthermia to be incorporated in the therapeutic armamentarium as a safe and an effective addendum to the existing oncological treatment modalities.

Association of acute adverse effects with high local SAR induced in the brain from prolonged RF head and neck hyperthermia.

To provide an adequate level of protection for humans from exposure to radio-frequency (RF) electromagnetic fields (EMF) and to assure that any adverse health effects are avoided. The basic restrictions in terms of the specific energy absorption rate (SAR) were prescribed by IEEE and ICNIRP. An example of a therapeutic application of non-ionizing EMF is hyperthermia (HT), in which intense RF energy is focused at a target region. Deep HT in the head and neck (H&N) region involves inducing energy at 434 MHz for 60 min on target. Still, stray exposure of the brain is considerable, but to date only very limited side-effects were observed. The objective of this study is to investigate the stringency of the current basic restrictions by relating the induced EM dose in the brain of patients treated with deep head and neck (H&N) HT to the scored acute health effects. We performed a simulation study to calculate the induced peak 10 g spatial-averaged SAR (psSAR10g) in the brains of 16 selected H&N patients who received the highest SAR exposure in the brain, i.e. who had the minimum brain-target distance and received high forwarded power during treatment. The results show that the maximum induced SAR in the brain of the patients can exceed the current basic restrictions (IEEE and ICNIRP) on psSAR10g for occupational environments by 14 times. Even considering the high local SAR in the brain, evaluation of acute effects by the common toxicity criteria (CTC) scores revealed no indication of a serious acute neurological effect. In addition, this study provides pioneering quantitative human data on the association between maximum brain SAR level and acute adverse effects when brains are exposed to prolonged RF EMF.

Laboratory prototype for experimental validation of MR-guided radiofrequency head and neck hyperthermia.

Clinical studies have established a strong benefit from adjuvant mild hyperthermia (HT) to radio- and chemotherapy for many tumor sites, including the head and neck (H&N). The recently developed HYPERcollar allows the application of local radiofrequency HT to tumors in the entire H&N. Treatment quality is optimized using electromagnetic and thermal simulators and, whenever placement risk is tolerable, assessed using invasively placed thermometers. To replace the current invasive procedure, we are investigating whether magnetic resonance (MR) thermometry can be exploited for continuous and 3D thermal dose assessment. In this work, we used our simulation tools to design an MR compatible laboratory prototype applicator. By simulations and measurements, we showed that the redesigned patch antennas are well matched to 50 Ω (S11<-10 dB). Simulations also show that, using 300 W input power, a maximum specific absorption rate (SAR) of 100 W kg(-1) and a temperature increase of 4.5 °C in 6 min is feasible at the center of a cylindrical fat/muscle phantom. Temperature measurements using the MR scanner confirmed the focused heating capabilities and MR compatibility of the setup. We conclude that the laboratory applicator provides the possibility for experimental assessment of the feasibility of hybrid MR-HT in the H&N region. This versatile design allows rigorous analysis of MR thermometry accuracy in increasingly complex phantoms that mimic patients' anatomies and thermodynamic characteristics.

Electromagnetic redesign of the HYPERcollar applicator: toward improved deep local head-and-neck hyperthermia.

Accumulating evidence shows that hyperthermia improves head-and-neck cancer treatment. Over the last decade, we introduced a radiofrequency applicator, named HYPERcollar, which enables local heating also of deep locations in this region. Based on clinical experience, we redesigned the HYPERcollar for improved comfort, reproducibility and operator handling. In the current study, we analyze the redesign from an electromagnetic point of view. We show that a higher number of antennas and their repositioning allow for a substantially improved treatment quality. Combined with the much better reproducibility of the water bolus, this will substantially minimize the risk of underexposure. All improvements combined enable a reduction of hot-spot prominence (hot-spot to target SAR quotient) by 32% at an average of 981 W, which drastically reduces the probability for system power to become a treatment limiting source. Moreover, the power deposited in the target selectively can be increased by more than twofold. Hence, we expect that the HYPERcollar redesign currently under construction allows us to double the clinically applied power to the target while reducing the hot-spots, resulting in higher temperatures and, consequently, better clinical outcome.

Predicting multiple sclerosis following isolated optic neuritis in children.

BACKGROUND AND PURPOSE: Isolated optic neuritis (ON) is frequently the initial symptom of multiple sclerosis (MS). The aim of our study was to investigate the risk of conversion to MS in children following isolated ON and to evaluate the performance of current diagnostic methods such as cranial magnetic resonance imaging (cMRI), visual evoked potentials (VEPs) and oligoclonal bands in spinal fluid (OCB) as predictive factors for MS development. METHODS: Medical records of 159 patients presenting with acute ON between 2000 and 2010 at the Department of Pediatrics, University of Erlangen, were screened; 34 patients with isolated ON were identified. Progression to MS was defined according to the revised McDonald criteria 2005. Age, sex, VEPs, ON type, cMRI, OCB and visual recovery were assessed as predictors of progression to MS using simple logistic regressions. A multiple logistic regression model included variables found to be significant in univariate analyses. RESULTS: Abnormal cMRI was associated with an increase in the odds of MS development (odds ratio 20.57; 95% CI 2.16-196.10, P < 0.001), as was positive OCB (odds ratio 12.0; 95% CI 1.29-111.32, P = 0.001). However, only cMRI remained statistically significant in multiple regressions. CONCLUSIONS: Multiple sclerosis-like cMRI lesions and OCB are suitable for assessing the risk of progression to MS following isolated ON, as children with both cMRI abnormalities and positive OCB at onset of ON are at high risk of developing MS.

Benefit of replacing the Sigma-60 by the Sigma-Eye applicator. A Monte Carlo-based uncertainty analysis.

BACKGROUND AND PURPOSE: To investigate the clinical benefit of replacing the BSD-2000 Sigma-60 with the Sigma-Eye applicator, taking into account effects of uncertainties in tissue and water bolus parameters. PATIENTS AND METHODS: For 20 patients, specific absorption rate (SAR) and temperature distributions were calculated and optimized, based on computed tomography (CT) scans in treatment position. The impact of uncertainties on predicted distributions was studied using a Monte Carlo uncertainty assessment. RESULTS: Replacing the Sigma-60 by the Sigma-Eye applicator resulted in a higher SAR in the tumor [on average a decrease of the hotspot tumor quotient (HTQ) by 24%; p < 0.001], and higher temperatures (T90: +0.4°C, p < 0.001; T50: +0.6°C, p < 0.001) using literature values and SAR optimization. When temperature optimization (T90) was used, a larger average increase was found (T90: +0.7°C, p < 0.001; T50: +0.8°C, p < 0.001). When taking into account uncertainties, a decrease of 23% in median HTQ (p < 0.001) and an increase in T50 and T90 of 0.4°C (p < 0.001) could be demonstrated. CONCLUSION: Based on this uncertainty analysis, significant and clinically relevant improvements in HTQ and tumor temperature were achieved when replacing the Sigma-60 by the Sigma-Eye applicator.

Reconstruction of applicator positions from multiple-view images for accurate superficial hyperthermia treatment planning.

In the current clinical practice, prior to superficial hyperthermia treatments (HT), temperature probes are placed in tissue to document a thermal dose. To investigate whether the painful procedure of catheter placement can be replaced by superficial HT planning, we study if the specific absorption rate (SAR) coverage is predictive for treatment outcome. An absolute requirement for such a study is the accurate reconstruction of the applicator setup. The purpose of this study was to investigate the feasibility of the applicator setup reconstruction from multiple-view images. The accuracy of the multiple-view reconstruction method has been assessed for two experimental setups using six lucite cone applicators (LCAs) representing the largest array applied at our clinic and also the most difficult scenario for the reconstruction. For the two experimental setups and 112 distances, the mean difference between photogrametry reconstructed and manually measured distances was 0.25 ± 0.79 mm (mean±1 standard deviation). By a parameter study of translation T (mm) and rotation R (°) of LCAs, we showed that these inaccuracies are clinically acceptable, i.e. they are either from ±1.02 mm error in translation or ±0.48° in rotation, or combinations expressed by 4.35R(2) + 0.97T(2) = 1. We anticipate that such small errors will not have a relevant influence on the SAR distribution in the treated region. The clinical applicability of the procedure is shown on a patient with a breast cancer recurrence treated with reirradiation plus superficial hyperthermia using the six-LCA array. The total reconstruction procedure of six LCAs from a set of ten photos currently takes around 1.5 h. We conclude that the reconstruction of superficial HT setup from multiple-view images is feasible and only minor errors are found that will have a negligible influence on treatment planning quality.

Children and adults exposed to low-frequency magnetic fields at the ICNIRP reference levels: theoretical assessment of the induced electric fields.

To avoid potentially adverse health effects, the International Commission on Non-Ionizing Radiation Protection (ICNIRP) has defined reference levels for time varying magnetic fields. Restrictions on the electric fields induced in the human body are provided based on biological response data for peripheral nerve stimulation and the induction of phosphenes. Numerical modeling is commonly used to assess the induced electric fields for various exposure configurations. The objective of this study was to assess the variations of the electric fields induced in children and adults and to compare the exposure at reference levels with the basic restrictions as function of anatomy. We used the scalar potential finite element method to calculate the induced electric fields in six children and two adults when exposed to uniform magnetic fields polarized in three orthogonal directions. We found that the induced electric fields are within the ICNIRP basic restrictions in nearly all cases. In PNS tissues, we found electric fields up to 95% (upper uncertainty limit due to discretization errors, k = 2) of the ICNIRP basic restrictions for exposures at the general public reference levels. For occupational reference levels, we found an over-exposure of maximum 79% (k = 2) in PNS tissues. We further found that the ICNIRP recommendations on spatial averaging in 2 × 2 × 2 mm³ contiguous tissue volumes and removal of peak values by the 99th percentile cause the results to depend strongly on the grid discretization step (i.e. an uncertainty of more than 50% at 2 mm) and the number of distinguished tissues in the anatomical models. The computational results obtained by various research institutes should be robust for different discretization settings and various anatomical models. Therefore, we recommend considering alternative routines for small anatomical structures such as non-contiguous averaging without taking the 99th percentile in future guidelines leading to consistent suppression of peak values amongst different simulation settings and anatomical models. The peak electric fields depend on the local tissue distribution in the various anatomical models, and we could not find a correlation with the size of the anatomy. Therefore, we recommend extending the evaluation using a sufficient set of anatomies including other than standing postures to assess the worst-case exposure setting and correspondence to the basic restrictions.

Children and adults exposed to electromagnetic fields at the ICNIRP reference levels: theoretical assessment of the induced peak temperature increase.

To avoid potentially adverse health effects of electromagnetic fields (EMF), the International Commission on Non-Ionizing Radiation Protection (ICNIRP) has defined EMF reference levels. Restrictions on induced whole-body-averaged specific absorption rate (SAR(wb)) are provided to keep the whole-body temperature increase (T(body, incr)) under 1 °C during 30 min. Additional restrictions on the peak 10 g spatial-averaged SAR (SAR(10g)) are provided to prevent excessive localized tissue heating. The objective of this study is to assess the localized peak temperature increase (T(incr, max)) in children upon exposure at the reference levels. Finite-difference time-domain modeling was used to calculate T(incr, max) in six children and two adults exposed to orthogonal plane-wave configurations. We performed a sensitivity study and Monte Carlo analysis to assess the uncertainty of the results. Considering the uncertainties in the model parameters, we found that a peak temperature increase as high as 1 °C can occur for worst-case scenarios at the ICNIRP reference levels. Since the guidelines are deduced from temperature increase, we used T(incr, max) as being a better metric to prevent excessive localized tissue heating instead of localized peak SAR. However, we note that the exposure time should also be considered in future guidelines. Hence, we advise defining limits on T(incr, max) for specified durations of exposure.