Ethylcellulose-stabilized fat-tissue phantom for quality assurance in clinical hyperthermia.

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.

Application of the ESHO-QA guidelines for determining the performance of the LCA superficial hyperthermia heating system.

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.

Patient-derived breast model repository, a tool for hyperthermia treatment planning and applicator design.

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 T10 = 43.5°C (41.9-43.8°C), T50 = 42.5°C (41.3-43.3°C), and T90 = 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.

Review of Thermal and Physiological Properties of Human Breast Tissue.

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.

ESHO benchmarks for computational modeling and optimization in hyperthermia therapy.

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.

How large is the periablational zone after radiofrequency and microwave ablation? Computer-based comparative study of two currently used clinical devices.

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 (Ω). CZ was considered when Ω > 4.6 (>99% of damaged cells). Regions with 0.6<Ω < 2.1 were considered as the PZ (tissue that has undergone moderate sub-ablative hyperthermia). The ratio of PZ volume to CZ volume (PZ/CZ) was regarded as a measure of performance, since a low value implies achieving a large CZ while keeping the PZ small. RESULTS: Ten-min RFA (51 W) created smaller periablational zones than 10-min MWA (11.3 cm3 vs. 17.2-22.9 cm3, for 60-100 W MWA, respectively). Prolonging duration from 5 to 10 min increased the PZ in MWA more than in RFA (2.7 cm3 for RFA vs. 8.3-11.9 cm3 for 60-100 W MWA, respectively). PZ/CZ for RFA were relatively high (65-69%), regardless of ablation time, while those for MWA were highly dependent on the duration (increase of up to 25% between 5 and 10 min) and on the applied power (smaller values as power was raised, 102% for 60 W vs. 81% for 100 W, both for 10 min). The lowest PZ/CZ across all settings was 56%, obtained with 100 W-5 min MWA. CONCLUSIONS: Although RFA creates smaller periablational zones than MWA, 100 W-5 min MWA provides the lowest PZ/CZ.

Systematic review of pre-clinical and clinical devices for magnetic resonance-guided radiofrequency hyperthermia.

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.

Standardization of patient modeling in hyperthermia simulation studies: introducing the Erasmus Virtual Patient Repository.

Purpose: Thermal dose-effect relations have demonstrated that clinical effectiveness of hyperthermia would benefit from more controlled heating of the tumor. Hyperthermia treatment planning (HTP) is a potent tool to study strategies enabling target conformal heating, but its accuracy is affected by patient modeling approximations. Homogeneous phantoms models are being used that do not match the body shape of patients in treatment position and often have unrealistic target volumes. As a consequence, simulation accuracy is affected, and performance comparisons are difficult. The aim of this study is to provide the first step toward standardization of HTP simulation studies in terms of patient modeling by introducing the Erasmus Virtual Patient Repository (EVPR): a virtual patient model database.Methods: Four patients with a tumor in the head and neck or the pelvis region were selected, and corresponding models were created using a clinical segmentation procedure. Using the Erasmus University Medical Center standard procedure, HTP was applied to these models and compared to HTP for commonly used surrogate models.Results: Although this study was aimed at presenting the EVPR database, our study illustrates that there is a non-negligible difference in the predicted SAR patterns between patient models and homogeneous phantom-based surrogate models. We further demonstrate the difference between actual and simplified target volumes being used today.Conclusion: Our study describes the EVPR for the research community as a first step toward standardization of hyperthermia simulation studies.

A multi-institution study: comparison of the heating patterns of five different MR-guided deep hyperthermia systems using an anthropomorphic phantom.

INTRODUCTION: Within the hyperthermia community, consensus exists that clinical outcome of the treatment radiotherapy and/or chemotherapy plus hyperthermia (i.e. elevating tumor temperature to 40 - 44 °C) is related to the applied thermal dose; hence, treatment quality is crucial for the success of prospective multi-institution clinical trials. Currently, applicator quality assurance (QA) measurements are implemented independently at each institution using basic cylindrical phantoms. A multi-institution comparison of heating quality using magnetic resonance thermometry (MRT) and anatomical representative anthropomorphic phantoms provides a unique opportunity to obtain novel QA insights to facilitate multi-institution trial evaluation. OBJECTIVE: Perform a systematic QA procedure to compare the performance of MR-compatible hyperthermia systems in five institutions. METHODS AND MATERIALS: Anthropomorphic phantoms, including pelvic and spinal bones, were produced. Clinically relevant power of 600 watts was applied for ∼12 min to allow for 8 sequential MR-scans. The 3D-heating distribution, steering capabilities, and presence of off-target heating were analyzed. RESULTS: The evaluated devices show comparable heating profiles for centric and eccentric targets. The differences observed in the 3D-heating profiles are the result of variations in the exact phantom positioning and applicator characteristics, whereby positioning of the phantom followed current ESHO-QA guidelines. CONCLUSION: Anthropomorphic phantoms were used to perform QA-measurements of MR-guided hyperthermia systems operating in MR-scanners of different brands. Comparable heating profiles are shown for the five evaluated institutions. Subcentimeter differences in position substantially affected the results when evaluating the heating patterns. Integration of advanced phantoms and precise positioning in QA-guidelines should be evaluated to guarantee the best quality patient care.

Thermal Characterization of Phantoms Used for Quality Assurance of Deep Hyperthermia Systems.

Tissue mimicking phantoms are frequently used in hyperthermia applications for device and protocol optimization. Unfortunately, a commonly experienced limitation is that their precise thermal properties are not available. Therefore, in this study, the thermal properties of three currently used QA phantoms for deep hyperthermia are measured with an "off-shelf" commercial thermal property analyzer. We have measured averaged values of thermal conductivity (k = 0.59 ± 0.07 Wm-1K-1), volumetric heat capacity (C = 3.85 ± 0.45 MJm-3K-1) and thermal diffusivity (D = 0.16 ± 0.02 mm2s-1). These values are comparable with reported values of internal organs, such as liver, kidney and muscle. In addition, a sensitivity study of the performance of the commercial sensor is conducted. To ensure correct thermal measurements, the sample under test should entirely cover the length of the sensor, and a minimum of 4 mm of material parallel to the sensor in all directions should be guaranteed.

Systematic quality assurance of the BSD2000-3D MR-compatible hyperthermia applicator performance using MR temperature imaging.

BACKGROUND: Radiofrequency (RF) mild hyperthermia (40 °C-44 °C for 60 minutes) is an effective adjuvant treatment for several types of cancer. To ensure treatment efficacy, quality assurance (QA) is necessary. This study presents the first systematic 3D characterisation of the heating performance of the commonly used Pyrexar BSD2000-3D MR-compatible hyperthermia applicator using magnetic resonance temperature imaging (MRTI). METHODS: A reproducibly positioned phantom was heated with a power of 1000 watts during the 12.4 min needed to measure eight temperature distributions using MRTI. The target heating location was systematically varied between experiments. We analysed focus shape characteristics, steering accuracy, focus deformation due to steering, presence of off-target heating and reproducibility. RESULTS: The mean maximum temperature increase was 5.9 ± 0.4 °C. The mean full width half maximum (FWHM) was 14.4 ± 0.5 cm in the XY plane and 24.5 ± 0.8 cm in Z-direction. The mean steering error was 0.4 ± 0.2 cm. The focus shape slightly varied between experiments, depending on steering distance in Y-direction. Off-target heating was not detected. Reproducibility of the focus amplitude and shape was determined by comparing the mean deviation from the mean temperature in the central slice was 0.3 ± 0.2 °C. CONCLUSION: The Pyrexar BSD2000-3D MR-compatible applicator provides robust and reproducible heating. The upper boundary of the 95% confidence interval of the spatial steering accuracy is 0.9 cm, i.e. sufficient to fulfil the criterion of ≤0.2 °C temperature variation due to positioning errors as defined by Canters et al.

Design and characterisation of a phased antenna array for intact breast hyperthermia.

PURPOSE: Currently available hyperthermia technology is not well suited to treating cancer malignancies in the intact breast. This study investigates a microwave applicator incorporating multiple patch antennas, with the goal of facilitating controllable power deposition profiles for treating lesions at diverse locations within the intact breast. MATERIALS AND METHODS: A 3D-computational model was implemented to assess power deposition profiles with 915 MHz applicators incorporating a hemispheric groundplane and configurations of 2, 4, 8, 12, 16 and 20 antennas. Hemispheric breast models of 90 mm and 150 mm diameter were considered, where cuboid target volumes of 10 mm edge length (1 cm3) and 30 mm edge length (27 cm3) were positioned at the centre of the breast, and also located 15 mm from the chest wall. The average power absorption (αPA) ratio expressed as the ratio of the PA in the target volume and in the full breast was evaluated. A 4-antenna proof-of-concept array was fabricated and experimentally evaluated. RESULTS: Computational models identified an optimal inter-antenna spacing of 22.5° along the applicator circumference. Applicators with 8 and 12 antennas excited with constant phase presented the highest αPA at centrally located and deep-seated targets, respectively. Experimental measurements with a 4-antenna proof-of-concept array illustrated the potential for electrically steering power deposition profiles by adjusting the relative phase of the signal at antenna inputs. CONCLUSIONS: Computational models and experimental results suggest that the proposed applicator may have potential for delivering conformal thermal therapy in the intact breast.

An integrated platform for small-animal hyperthermia investigations under ultra-high-field MRI guidance.

PURPOSE: Integrating small-animal experimental hyperthermia instrumentation with magnetic resonance imaging (MRI) affords real-time monitoring of spatial temperature profiles. This study reports on the development and preliminary in vivo characterisation of a 2.45 GHz microwave hyperthermia system for pre-clinical small animal investigations, integrated within a 14 T ultra-high-field MRI scanner. MATERIALS AND METHODS: The presented system incorporates a 3.5 mm (OD) directional microwave hyperthermia antenna, positioned adjacent to the small-animal target, radiating microwave energy for localised heating of subcutaneous tumours. The applicator is integrated within the 30 mm bore of the MRI system. 3D electromagnetic and biothermal simulations were implemented to characterise hyperthermia profiles from the directional microwave antenna. Experiments in tissue mimicking phantoms were performed to assess hyperthermia profiles and validate MR thermometry against fibre-optic temperature measurements. The feasibility of delivering in vivo hyperthermia exposures to subcutaneous 4T1 tumours in experimental mice under simultaneous MR thermometry guidance was assessed. RESULTS: Simulations and experiments in tissue mimicking phantoms demonstrated the feasibility of heating 21-982 mm3 targets with 8-12 W input power. Minimal susceptibility and electrical artefacts introduced by the hyperthermia applicator were observed on MR imaging. MR thermometry was in excellent agreement with fibre-optic temperatures measurements (max. discrepancy ≤0.6 °C). Heating experiments with the reported system demonstrated the feasibility of heating subcutaneous tumours in vivo with simultaneous MR thermometry. CONCLUSIONS: A platform for small-animal hyperthermia investigations under ultra-high-field MR thermometry was developed and applied to heating subcutaneous tumours in vivo.

Quality assurance guidelines for superficial hyperthermia clinical trials : II. Technical requirements for heating devices.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.

Analysis of minimally invasive directional antennas for microwave tissue ablation.

PURPOSE: Microwave ablation (MWA) applicators capable of creating directional heating patterns offer the potential of simplifying treatment of targets in proximity to critical structures and avoiding the need for piercing the tumour volume. This work reports on improved directional MWA antennas with the objectives of minimising device diameter for percutaneous use (≤ ∼13 gauge) and yielding larger ablation zones. METHODS: Two directional MWA antenna designs, with a modified monopole radiating element and spherical and parabolic reflectors are proposed. A 3D-coupled electromagnetic heat transfer with temperature-dependent material properties was implemented to characterise MWA at 40 and 77 W, for 5 and 10 min. Simulations were also used to assess antenna impedance matching within liver, kidney, lung, bone and brain tissue. The two antenna designs were fabricated and experimentally evaluated with ablations in ex vivo tissue at the two power levels and treatment durations (n = 5 repetitions for each group). RESULTS: The computed specific absorption rate (SAR) patterns for both antennas were similar, although simulations indicated slightly greater forward penetration for the parabolic antenna. Based on simulations for antennas inserted within different tissues, the proposed antenna design appears to offer good impedance matching for a variety of tissue types. Experiments in ex vivo tissue showed radial ablation depths of 19 ± 0.9 mm in the forward direction for the applicator with spherical reflector and 18.7 ± 0.7 mm for the applicator with parabolic reflector. CONCLUSION: These results suggest the applicator may be suitable for creating localised directional ablation zones for treating small and medium-sized targets with a percutaneous approach.

Design of a compact antenna with flared groundplane for a wearable breast hyperthermia system.

PURPOSE: Currently available microwave hyperthermia systems for breast cancer treatment do not conform to the intact breast and provide limited control of heating patterns, thereby hindering an effective treatment. A compact patch antenna with a flared groundplane that may be integrated within a wearable hyperthermia system for the treatment of the intact breast disease is proposed. MATERIALS AND METHODS: A 3D simulation-based approach was employed to optimise the antenna design with the objective of maximising the hyperthermia treatment volume (41 °C iso-therm) while maintaining good impedance matching. The optimised antenna design was fabricated and experimentally evaluated with ex vivo tissue measurements. RESULTS: The optimised compact antenna yielded a -10 dB bandwidth of 90 MHz centred at 915 MHz, and was capable of creating hyperthermia treatment volumes up to 14.4 cm(3) (31 mm × 28 mm × 32 mm) with an input power of 15 W. Experimentally measured reflection coefficient and transient temperature profiles were in good agreement with simulated profiles. Variations of + 50% in blood perfusion yielded variations in the treatment volume up to 11.5%. When compared to an antenna with a similar patch element employing a conventional rectangular groundplane, the antenna with flared groundplane afforded 22.3% reduction in required power levels to reach the same temperature, and yielded 2.4 times larger treatment volumes. CONCLUSION: The proposed patch antenna with a flared groundplane may be integrated within a wearable applicator for hyperthermia treatment of intact breast targets and has the potential to improve efficiency, increase patient comfort, and ultimately clinical outcomes.

Avoiding Pitfalls in Thermal Dose Effect Relationship Studies: A Review and Guide Forward.

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.

POD-Kalman filtering for improving noninvasive 3D temperature monitoring in MR-guided hyperthermia.

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 match between temperature prediction and temperature acquired by intraluminal thermometry for patients treated for locally advanced cervical cancer. Considering all patients, the POD-Kalman filter improved MAE by 43% (filtered MR thermometry = 1.29°C, POD-Kalman filtered temperature = 0.74°C). Moreover, the SDE was improved by 47% (filtered MR thermometry = 1.16°C, POD-Kalman filtered temperature = 0.61°C). Specifically, the POD-Kalman filter reduced the MAE by approximately 60% in patients whose MR thermometry was unreliable because of the great amount of susceptibilities caused by the high level of intestinal gas motion. CONCLUSIONS: We showed that the POD-Kalman filter significantly improved the accuracy of temperature monitoring compared to MR thermometry in heating experiments and hyperthermia treatments. The results demonstrated that POD-Kalman filtering can improve thermal dosimetry during RF hyperthermia treatment, especially when MR thermometry is inaccurate.

MR Thermometry Accuracy and Prospective Imaging-Based Patient Selection in MR-Guided Hyperthermia Treatment for Locally Advanced Cervical Cancer.

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.

External Basic Hyperthermia Devices for Preclinical Studies in Small Animals.

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.