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As research and development in the field of electro-magnetic medical devices increases, so does the need for proper validation and calibration. This is typically done using tissue mimicking models known as phantoms. Magnetic resonance imaging (MRI) is becoming increasingly popular for electro-magnetic device modelling and validation. Currently, there is no muscle phantom material that matches the properties of muscle tissue in MRI, electromagnetic and thermal properties. This study presents a novel muscle phantom made from inexpensive, household materials, that can approximate all three. Phantoms consist of water, agar-agar, peanut oil, and protein powder. These ingredients are used to model healthy, obese and dehydrated muscle tissue. While the phantoms exhibit behavior similar to those in existing literature, their values are consistently lower. We expect that future improvement is possible by reducing the protein and oil content, to bring the values even closer to the muscle tissue properties reported in literature.

Purpose: This study aimed to assess the quality of the lucite cone applicator (LCA), the standard applicator for superficial hyperthermia at the Erasmus MC Cancer Institute, using the most recent quality assurance guidelines, thus verifying their feasibility. Materials and methods: The assessment was conducted on each of the six LCAs available for clinical treatments. The temperature distribution was evaluated using an infrared camera across different layers of a fat-muscle mimicking phantom. The maximum temperature increase, thermal effective penetration depth (TEPD), and thermal effective field size (TEFS) were used as quality metrics. The experimental results were validated through comparison with simulated results, using a canonical phantom model and a realistic phantom model segmented from CT imaging. Results: A maximum temperature increase above 6 °C at 2 cm depth in the fat-muscle phantom for all the experiments was found. A mean negative difference between simulated and experimental data was of 1.3 °C when using the canonical phantom model. This value decreased to a mean negative difference of 0.4 °C when using the realistic model. Simulated and measured TEPD showed good agreement for both in silico scenarios, while discrepancies were present for TEFS. Conclusions: The LCAs passed all QA guidelines requirements for superficial hyperthermia delivery when used singularly or in an array configuration. A further characterization of parameters such as antenna efficiency and heat transfer coefficients would be beneficial for translating experimental results to simulated values. Implementing the QA guidelines was time-consuming and demanding, requiring careful preparation and correct setup of antenna elements.

Purpose: This study aimed to assess the quality of the lucite cone applicator (LCA), the standard applicator for superficial hyperthermia at the Erasmus MC Cancer Institute, using the most recent quality assurance guidelines, thus verifying their feasibility. Materials and methods: The assessment was conducted on each of the six LCAs available for clinical treatments. The temperature distribution was evaluated using an infrared camera across different layers of a fat-muscle mimicking phantom. The maximum temperature increase, thermal effective penetration depth (TEPD), and thermal effective field size (TEFS) were used as quality metrics. The experimental results were validated through comparison with simulated results, using a canonical phantom model and a realistic phantom model segmented from CT imaging. Results: A maximum temperature increase above 6 °C at 2 cm depth in the fat-muscle phantom for all the experiments was found. A mean negative difference between simulated and experimental data was of 1.3 °C when using the canonical phantom model. This value decreased to a mean negative difference of 0.4 °C when using the realistic model. Simulated and measured TEPD showed good agreement for both in silico scenarios, while discrepancies were present for TEFS. Conclusions: The LCAs passed all QA guidelines requirements for superficial hyperthermia delivery when used singularly or in an array configuration. A further characterization of parameters such as antenna efficiency and heat transfer coefficients would be beneficial for translating experimental results to simulated values. Implementing the QA guidelines was time-consuming and demanding, requiring careful preparation and correct setup of antenna elements., RST/Applied Radiation & Isotopes

Background: Phantoms accurately mimicking the electromagnetic and thermal properties of human tissues are essential for the development, characterization, and quality assurance (QA) of clinically used equipment for Hyperthermia Treatment (HT). Currently, a viable recipe for a fat equivalent phantom is not available, mainly due to challenges in the fabrication process and fast deterioration. Materials and methods: We propose to employ a glycerol-in-oil emulsion stabilized with ethylcellulose to develop a fat-mimicking material. The dielectric, rheological, and thermal properties of the phantom have been assessed by state-of-the-art measurement techniques. The full-size phantom was then verified in compliance with QA guidelines for superficial HT, both numerically and experimentally, considering the properties variability. Results: Dielectric and thermal properties were proven equivalent to fat tissue, with an acceptable variability, in the 8 MHz to 1 GHz range. The rheology measurements highlighted enhanced mechanical stability over a large temperature range. Both numerical and experimental evaluations proved the suitability of the phantom for QA procedures. The impact of the dielectric property variations on the temperature distribution has been numerically proven to be limited (around 5%), even if higher for capacitive devices (up to 20%). Conclusions: The proposed fat-mimicking phantom is a good candidate for hyperthermia technology assessment processes, adequately representing both dielectric and thermal properties of the human fat tissue while maintaining structural stability even at elevated temperatures. However, further experimental investigations on capacitive heating devices are necessary to better assess the impact of the low electrical conductivity values on the thermal distribution.

Background: During resonance frequency (RF) hyperthermia treatment, the temperature of the tumor tissue is elevated to the range of 39–44°C. Accurate temperature monitoring is essential to guide treatments and ensure precise heat delivery and treatment quality. Magnetic resonance (MR) thermometry is currently the only clinical method to measure temperature noninvasively in a volume during treatment. However, several studies have shown that this approach is not always sufficiently accurate for thermal dosimetry in areas with motion, such as the pelvic region. Model-based temperature estimation is a promising approach to correct and supplement 3D online temperature estimation in regions where MR thermometry is unreliable or cannot be measured. However, complete 3D temperature modeling of the pelvic region is too complex for online usage. Purpose: This study aimed to evaluate the use of proper orthogonal decomposition (POD) model reduction combined with Kalman filtering to improve temperature estimation using MR thermometry. Furthermore, we assessed the benefit of this method using data from hyperthermia treatment where there were limited and unreliable MR thermometry measurements. Methods: The performance of POD–Kalman filtering was evaluated in several heating experiments and for data from patients treated for locally advanced cervical cancer. For each method, we evaluated the mean absolute error (MAE) concerning the temperature measurements acquired by the thermal probes, and we assessed the reproducibility and consistency using the standard deviation of error (SDE). Furthermore, three patient groups were defined according to susceptibility artifacts caused by the level of intestinal gas motion to assess if the POD–Kalman filtering could compensate for missing and unreliable MR thermometry measurements. Results: First, we showed that this method is beneficial and reproducible in phantom experiments. Second, we demonstrated that the combined method improved the ma, RST/Applied Radiation & Isotopes

Background: During resonance frequency (RF) hyperthermia treatment, the temperature of the tumor tissue is elevated to the range of 39–44°C. Accurate temperature monitoring is essential to guide treatments and ensure precise heat delivery and treatment quality. Magnetic resonance (MR) thermometry is currently the only clinical method to measure temperature noninvasively in a volume during treatment. However, several studies have shown that this approach is not always sufficiently accurate for thermal dosimetry in areas with motion, such as the pelvic region. Model-based temperature estimation is a promising approach to correct and supplement 3D online temperature estimation in regions where MR thermometry is unreliable or cannot be measured. However, complete 3D temperature modeling of the pelvic region is too complex for online usage. Purpose: This study aimed to evaluate the use of proper orthogonal decomposition (POD) model reduction combined with Kalman filtering to improve temperature estimation using MR thermometry. Furthermore, we assessed the benefit of this method using data from hyperthermia treatment where there were limited and unreliable MR thermometry measurements. Methods: The performance of POD–Kalman filtering was evaluated in several heating experiments and for data from patients treated for locally advanced cervical cancer. For each method, we evaluated the mean absolute error (MAE) concerning the temperature measurements acquired by the thermal probes, and we assessed the reproducibility and consistency using the standard deviation of error (SDE). Furthermore, three patient groups were defined according to susceptibility artifacts caused by the level of intestinal gas motion to assess if the POD–Kalman filtering could compensate for missing and unreliable MR thermometry measurements. Results: First, we showed that this method is beneficial and reproducible in phantom experiments. Second, we demonstrated that the combined method improved the ma

OBJECTIVE: The addition of hyperthermia in the treatment of intact breast cancer with the aim to improve local response is currently in a research phase. First, optimal hyperthermia devices need to be developed, for which a diverse, anatomically and pathologically accurate set of patient models is necessary.METHODS: To investigate the effects of inter-subject variations on hyperthermia treatment plans, we generated a repository of 22 anatomically and pathologically diverse patient models based on MR images of breast cancer patients. Hyperthermia treatment plans were generated for the 22 models using a generic theoretical phased array hyperthermia applicator.RESULTS: Good temperature coverage was achieved in the vast majority of the models, with median values for T 10 = 43.5°C (41.9-43.8°C), T 50 = 42.5°C (41.3-43.3°C), and T 90 = 41.3°C (39.8-42.6°C) under the condition that the maximum temperature increase in the patient is limited to 44°C. CONCLUSIONS: For future development of hyperthermia devices and treatment methods, a repository with a sufficiently large number of representative patient models, such as the one provided in this study, should be used to ensure applicability to a wide variety of patients. This repository is therefore made publicly available.

The challenge to explain the diffuse and unconclusive message reported by hyperthermia studies investigating the thermal dose parameter is still to be unravelled. In the present review, we investigated a wide range of technical and clinical parameters characterising hyperthermia treatment to better understand and improve the probability of detecting a thermal dose effect relationship in clinical studies. We performed a systematic literature review to obtain hyperthermia clinical studies investigating the associations of temperature and thermal dose parameters with treatment outcome or acute toxicity. Different hyperthermia characteristics were retrieved, and their influence on temperature and thermal dose parameters was assessed. In the literature, we found forty-eight articles investigating thermal dose effect relationships. These comprised a total of 4107 patients with different tumour pathologies. The association between thermal dose and treatment outcome was the investigated endpoint in 90% of the articles, while the correlation between thermal dose and toxicity was investigated in 50% of the articles. Significant associations between temperature-related parameters and treatment outcome were reported in 63% of the studies, while those between temperature-related parameters and toxicity were reported in 15% of the studies. One clear difficulty for advancement is that studies often omitted fundamental information regarding the clinical treatment, and among the different characteristics investigated, thermometry details were seldom and divergently reported. To overcome this, we propose a clear definition of the terms and characteristics that should be reported in clinical hyperthermia treatments. A consistent report of data will allow their use to further continue the quest for thermal dose effect relationships.

Electromagnetic thermal therapies for cancer treatment, such as microwave hyperthermia, aim to heat up a targeted tumour site to temperatures within 40 and 44 °C. Computational simulations used to investigate such heating systems employ the Pennes' bioheat equation to model the heat exchange within the tissue, which accounts for several tissue properties: density, specific heat capacity, thermal conductivity, metabolic heat generation rate, and blood perfusion rate. We present a review of these thermal and physiological properties relevant for hyperthermia treatments of breast including fibroglandular breast, fatty breast, and breast tumours. The data included in this review were obtained from both experimental measurement studies and estimated properties of human breast tissues. The latter were used in computational studies of breast thermal treatments. The measurement methods, where available, are discussed together with the estimations and approximations considered for values where measurements were unavailable. The review concludes that measurement data for the thermal and physiological properties of breast and tumour tissue are limited. Fibroglandular and fatty breast tissue properties are often approximated from those of generic muscle or fat tissue. Tumour tissue properties are mostly obtained from approximating equations or assumed to be the same as those of glandular tissue. We also present a set of reliable data, which can be used for more accurate modelling and simulation studies to better treat breast cancer using thermal therapies.

Background During resonance frequency (RF) hyperthermia treatment, the temperature of the tumor tissue is elevated to the range of 39–44°C. Accurate temperature monitoring is essential to guide treatments and ensure precise heat delivery and treatment quality. Magnetic resonance (MR) thermometry is currently the only clinical method to measure temperature noninvasively in a volume during treatment. However, several studies have shown that this approach is not always sufficiently accurate for thermal dosimetry in areas with motion, such as the pelvic region. Model-based temperature estimation is a promising approach to correct and supplement 3D online temperature estimation in regions where MR thermometry is unreliable or cannot be measured. However, complete 3D temperature modeling of the pelvic region is too complex for online usage. Purpose This study aimed to evaluate the use of proper orthogonal decomposition (POD) model reduction combined with Kalman filtering to improve temperature estimation using MR thermometry. Furthermore, we assessed the benefit of this method using data from hyperthermia treatment where there were limited and unreliable MR thermometry measurements. Methods The performance of POD–Kalman filtering was evaluated in several heating experiments and for data from patients treated for locally advanced cervical cancer. For each method, we evaluated the mean absolute error (MAE) concerning the temperature measurements acquired by the thermal probes, and we assessed the reproducibility and consistency using the standard deviation of error (SDE). Furthermore, three patient groups were defined according to susceptibility artifacts caused by the level of intestinal gas motion to assess if the POD–Kalman filtering could compensate for missing and unreliable MR thermometry measurements. Results First, we showed that this method is beneficial and reproducible in phantom experiments. Second, we demonstrated that

The challenge to explain the diffuse and unconclusive message reported by hyperthermia studies investigating the thermal dose parameter is still to be unravelled. In the present review, we investigated a wide range of technical and clinical parameters characterising hyperthermia treatment to better understand and improve the probability of detecting a thermal dose effect relationship in clinical studies. We performed a systematic literature review to obtain hyperthermia clinical studies investigating the associations of temperature and thermal dose parameters with treatment outcome or acute toxicity. Different hyperthermia characteristics were retrieved, and their influence on temperature and thermal dose parameters was assessed. In the literature, we found forty-eight articles investigating thermal dose effect relationships. These comprised a total of 4107 patients with different tumour pathologies. The association between thermal dose and treatment outcome was the investigated endpoint in 90% of the articles, while the correlation between thermal dose and toxicity was investigated in 50% of the articles. Significant associations between temperature-related parameters and treatment outcome were reported in 63% of the studies, while those between temperature-related parameters and toxicity were reported in 15% of the studies. One clear difficulty for advancement is that studies often omitted fundamental information regarding the clinical treatment, and among the different characteristics investigated, thermometry details were seldom and divergently reported. To overcome this, we propose a clear definition of the terms and characteristics that should be reported in clinical hyperthermia treatments. A consistent report of data will allow their use to further continue the quest for thermal dose effect relationships., RST/Applied Radiation & Isotopes

Objective: The addition of hyperthermia in the treatment of intact breast cancer with the aim to improve local response is currently in a research phase. First, optimal hyperthermia devices need to be developed, for which a diverse, anatomically and pathologically accurate set of patient models is necessary. Methods: To investigate the effects of inter-subject variations on hyperthermia treatment plans, we generated a repository of 22 anatomically and pathologically diverse patient models based on MR images of breast cancer patients. Hyperthermia treatment plans were generated for the 22 models using a generic theoretical phased array hyperthermia applicator. Results: Good temperature coverage was achieved in the vast majority of the models, with median values for T 10 = 43.5°C (41.9–43.8°C), T 50 = 42.5°C (41.3–43.3°C), and T 90 = 41.3°C (39.8–42.6°C) under the condition that the maximum temperature increase in the patient is limited to 44°C. Conclusions: For future development of hyperthermia devices and treatment methods, a repository with a sufficiently large number of representative patient models, such as the one provided in this study, should be used to ensure applicability to a wide variety of patients. This repository is therefore made publicly available., RST/Applied Radiation & Isotopes

BACKGROUND: The success of cancer hyperthermia (HT) treatments is strongly dependent on the temperatures achieved in the tumor and healthy tissues as it correlates with treatment efficacy and safety, respectively. Hyperthermia treatment planning (HTP) simulations have become pivotal for treatment optimization due to the possibility for pretreatment planning, optimization and decision making, as well as real-time treatment guidance.MATERIALS AND METHODS: The same computational methods deployed in HTP are also used for in silico studies. These are of great relevance for the development of new HT devices and treatment approaches. To aid this work, 3 D patient models have been recently developed and made available for the HT community. Unfortunately, there is no consensus regarding tissue properties, simulation settings, and benchmark applicators, which significantly influence the clinical relevance of computational outcomes.RESULTS AND DISCUSSION: Herein, we propose a comprehensive set of applicator benchmarks, efficacy and safety optimization algorithms, simulation settings and clinical parameters, to establish benchmarks for method comparison and code verification, to provide guidance, and in view of the 2021 ESHO Grand Challenge (Details on the ESHO grand challenge on HTP will be provided at https://www.esho.info/).CONCLUSION: We aim to establish guidelines to promote standardization within the hyperthermia community such that novel approaches can quickly prove their benefit as quickly as possible in clinically relevant simulation scenarios. This paper is primarily focused on radiofrequency and microwave hyperthermia but, since 3 D simulation studies on heating with ultrasound are now a reality, guidance as well as a benchmark for ultrasound-based hyperthermia are also included.

The efficacy of a hyperthermia treatment depends on the delivery of well-controlled heating; hence, accurate temperature monitoring is essential for ensuring effective treatment. For deep pelvic hyperthermia, there are no comprehensive and systematic reports on MR thermometry. Moreover, data inclusion generally lacks objective selection criteria leading to a high probability of bias when comparing results. Herein, we studied whether imaging-based data inclusion predicts accuracy and could serve as a tool for prospective patient selection. The accuracy of the MR thermometry in patients with locally advanced cervical cancer was benchmarked against intraluminal temperature. We found that gastrointestinal air motion at the start of the treatment, quantified by the Jaccard similarity coefficient, was a good predictor for MR thermometry accuracy. The results for the group that was selected for low gastrointestinal air motion improved compared to the results for all patients by 50% (accuracy), 26% (precision), and 80% (bias). We found an average MR thermometry accuracy of 2.0 °C when all patients were considered and 1.0 °C for the selected group. These results serve as the basis for comprehensive benchmarking of novel technologies. The Jaccard similarity coefficient also has good potential to prospectively determine in which patients the MR thermometry will be valuable., RST/Applied Radiation & Isotopes

The efficacy of a hyperthermia treatment depends on the delivery of well-controlled heating; hence, accurate temperature monitoring is essential for ensuring effective treatment. For deep pelvic hyperthermia, there are no comprehensive and systematic reports on MR thermometry. Moreover, data inclusion generally lacks objective selection criteria leading to a high probability of bias when comparing results. Herein, we studied whether imaging-based data inclusion predicts accuracy and could serve as a tool for prospective patient selection. The accuracy of the MR thermometry in patients with locally advanced cervical cancer was benchmarked against intraluminal temperature. We found that gastrointestinal air motion at the start of the treatment, quantified by the Jaccard similarity coefficient, was a good predictor for MR thermometry accuracy. The results for the group that was selected for low gastrointestinal air motion improved compared to the results for all patients by 50% (accuracy), 26% (precision), and 80% (bias). We found an average MR thermometry accuracy of 2.0 °C when all patients were considered and 1.0 °C for the selected group. These results serve as the basis for comprehensive benchmarking of novel technologies. The Jaccard similarity coefficient also has good potential to prospectively determine in which patients the MR thermometry will be valuable.

This paper presents three devices suitable for the preclinical application of hyperthermia via the simultaneous high-resolution imaging of intratumoral events. (Pre)clinical studies have con-firmed that the tumor micro-environment is sensitive to the application of local mild hyperthermia. Therefore, heating is a promising adjuvant to aid the efficacy of radiotherapy or chemotherapy. More so, the application of mild hyperthermia is a useful stimulus for triggered drug release from heat-sensitive nanocarriers. The response of thermosensitive nanoparticles to hyperthermia and en-suing intratumoral kinetics are considerably complex in both space and time. To obtain better insight into intratumoral processes, longitudinal imaging (preferable in high spatial and temporal resolution) is highly informative. Our devices are based on (i) an external electric heating adaptor for the dorsal skinfold model, (ii) targeted radiofrequency application, and (iii) a microwave an-tenna for heating of internal tumors. These models, while of some technical complexity, significantly add to the understanding of effects of mild hyperthermia warranting implementation in research on hyperthermia.

Preclinical studies have shown that application of mild hyperthermia (40–43 °C) is a promising adjuvant to solid tumor treatment. To improve preclinical testing, enhance reproducibility, and allow comparison of the obtained results, it is crucial to have standardization of the available methods. Reproducibility of methods in and between research groups on the same techniques is crucial to have a better prediction of the clinical outcome and to improve new treatment strategies (for instance with heat‐sensitive nanoparticles). Here we provide a preclinically oriented review on the use and applicability of basic hyperthermia systems available for solid tumor thermal treatment in small animals. The complexity of these techniques ranges from a simple, low‐cost water bath approach, irradiation with light or lasers, to advanced ultrasound and capacitive heating devices.

[EN] Purpose To compare the size of the coagulation (CZ) and periablational (PZ) zones created with two commercially available devices in clinical use for radiofrequency (RFA) and microwave ablation (MWA), respectively. Methods Computer models were used to simulate RFA with a 3-cm Cool-tip applicator and MWA with an Amica-Gen applicator. The Arrhenius model was used to compute the damage index (omega). CZ was considered when omega > 4.6 (>99% of damaged cells). Regions with 0.6

Clinical trials have demonstrated the therapeutic benefits of adding radiofrequency (RF) hyperthermia (HT) as an adjuvant to radio- and chemotherapy. However, maximum utilization of these benefits is hampered by the current inability to maintain the temperature within the desired range. RF HT treatment quality is usually monitored by invasive temperature sensors, which provide limited data sampling and are prone to infection risks. Magnetic resonance (MR) temperature imaging has been developed to overcome these hurdles by allowing noninvasive 3D temperature monitoring in the target and normal tissues. To exploit this feature, several approaches for inserting the RF heating devices into the MR scanner have been proposed over the years. In this review, we summarize the status quo in MR-guided RF HT devices and analyze trends in these hybrid hardware configurations. In addition, we discuss the various approaches, extract best practices and identify gaps regarding the experimental validation procedures for MR - RF HT, aimed at converging to a common standard in this process.