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.

Application of photogrammetry reconstruction for hyperthermia quality control measurements.

PURPOSE: Hyperthermia is a cancer treatment in which the target region is heated to temperatures of 40-44 °C usually applying external electromagnetic field sources. The behavior of the hyperthermia applicators (antennas) in clinical practice should be periodically checked with phantom experiments to verify the applicator's performance over time. The purpose of this study was to investigate the application of photogrammetry reconstructions of 3D applicator position in these quality control procedure measurements. METHODS: Photogrammetry reconstruction was applied at superficial hyperthermia scenario using the Lucite cone applicator (LCA) and phased-array heating in the head and neck region using the HYPERcollar3D. Wire-frame models of the entire measurement setups were created from multiple-view images and used for recreation of the setup inside 3D electromagnetic field simulation software. We evaluated applicator relation (Ra) between measured and simulated absolute specific absorption rate (SAR) for manually created and photogrammetry reconstructed simulation setups. RESULTS: We found a displacement of 7.9 mm for the LCA and 8.2 mm for the HYPERcollar3D setups when comparing manually created and photogrammetry reconstructed applicator models placements. Ra improved from 1.24 to 1.18 for the LCA and from 1.17 to 1.07 for the HYPERcollar3D when using photogrammetry reconstructed simulation setups. CONCLUSION: Photogrammetry reconstruction technique holds promise to improve measurement setup reconstruction and agreement between measured and simulated absolute SAR.

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.

Simulation guided design of the MRcollar: a MR compatible applicator for deep heating in the head and neck region.

PURPOSE: To develop a head and neck hyperthermia phased array system compatible with a 1.5 T magnetic resonance (MR) scanner for noninvasive thermometry. METHODS: We designed a dielectric-parabolic-reflector antenna (DiPRA) based on a printed reflector backed dipole antenna and studied its predicted and measured performance in a flat configuration (30 mm thick water bolus and muscle equivalent layer). Thereafter, we designed a phased array applicator model ('MRcollar') consisting of 12 DiPRA modules placed on a radius of 180 mm. Theoretical heating performance of the MRcollar model was benchmarked against the current clinical applicator (HYPERcollar3D) using specific (3D) head and neck models of 28 treated patients. Lastly, we assessed the influence of the DiPRA modules on MR scanning quality. RESULTS: The predicted and measured reflection coefficients (S11) of the DiPRA module are below -20 dB. The maximum specific absorption rate (SAR) in the area under the antenna was 47% higher than for the antenna without encasing. Compared to the HYPERcollar3D, the MRcollar design incorporates 31% less demineralized water (-2.5 L), improves the predicted TC25 (target volume enclosed by 25% iso-SAR contour) by 4.1% and TC50 by 8.5%, while the target-to-hotspot quotient (THQ) is minimally affected (-1.6%). MR experiments showed that the DiPRA modules do not affect MR transmit/receive performance. CONCLUSION: Our results suggest that head and neck hyperthermia delivery quality with the MRcollar can be maintained, while facilitating simultaneous noninvasive MR thermometry for treatment monitoring and control.

Dual-Function MR-Guided Hyperthermia: An Innovative Integrated Approach and Experimental Demonstration of Proof of Principle.

Temperature monitoring plays a central role in improving clinical effectiveness of adjuvant hyperthermia. The potential of magnetic resonance thermometry for treatment monitoring purposes led to several MR-guided hyperthermia approaches. However, the proposed solutions were sub-optimal due to technological and intrinsic limitations. These hamper achieving target conformal heating possibilities (applicator limitations) and accurate thermometry (inadequate signal-to-noise-ratio (SNR)). In this work, we studied proof of principle of a dual-function hyperthermia approach based on a coil array (64 MHz, 1.5 T) that is integrated in-between a phased array for heating (434 MHz) for maximum signal receive in order to improve thermometry accuracy. Hereto, we designed and fabricated a superficial hyperthermia mimicking planar array setup to study the most challenging interactions of generic phased-array setups in order to validate the integrated approach. Experiments demonstrated that the setup complies with the superficial hyperthermia guidelines for heating and is able to improve SNR at 2-4 cm depth by 17%, as compared to imaging using the body coil. Hence, the results showed the feasibility of our dual-function MR-guided hyperthermia approach as basis for the development of application specific setups.

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.

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.

The Potential of Adjusting Water Bolus Liquid Properties for Economic and Precise MR Thermometry Guided Radiofrequency Hyperthermia.

The potential of MR thermometry (MRT) fostered the development of MRI compatible radiofrequency (RF) hyperthermia devices. Such device integration creates major technological challenges and a crucial point for image quality is the water bolus (WB). The WB is located between the patient body and external sources to both couple electromagnetic energy and to cool the patient skin. However, the WB causes MRT errors and unnecessarily large field of view. In this work, we studied making the WB MRI transparent by an optimal concentration of compounds capable of modifying T 2 * relaxation without an impact on the efficiency of RF heating. Three different T 2 * reducing compounds were investigated, namely CuSO 4 , MnCl 2 , and Fe 3 O 4 . First, electromagnetic properties and T 2 * relaxation rates at 1.5 T were measured. Next, through multi-physics simulations, the predicted effect on the RF-power deposition pattern was evaluated and MRT precision was experimentally assessed. Our results identified 5 mM Fe 3 O 4 solution as optimal since it does not alter the RF-power level needed and improved MRT precision from 0.39 ∘ C to 0.09 ∘ C. MnCl 2 showed a similar MRT improvement, but caused unacceptable RF-power losses. We conclude that adding Fe 3 O 4 has significant potential to improve RF hyperthermia treatment monitoring under MR guidance.

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.

Feasibility and relevance of discrete vasculature modeling in routine hyperthermia treatment planning.

Purpose: To investigate the effect of patient specific vessel cooling on head and neck hyperthermia treatment planning (HTP). Methods and materials: Twelve patients undergoing radiotherapy were scanned using computed tomography (CT), magnetic resonance imaging (MRI) and contrast enhanced MR angiography (CEMRA). 3D patient models were constructed using the CT and MRI data. The arterial vessel tree was constructed from the MRA images using the 'graph-cut' method, combining information from Frangi vesselness filtering and region growing, and the results were validated against manually placed markers in/outside the vessels. Patient specific HTP was performed and the change in thermal distribution prediction caused by arterial cooling was evaluated by adding discrete vasculature (DIVA) modeling to the Pennes bioheat equation (PBHE). Results: Inclusion of arterial cooling showed a relevant impact, i.e., DIVA modeling predicts a decreased treatment quality by on average 0.19 °C (T90), 0.32 °C (T50) and 0.35 °C (T20) that is robust against variations in the inflow blood rate (|ΔT| < 0.01 °C). In three cases, where the major vessels transverse target volume, notable drops (|ΔT| > 0.5 °C) were observed. Conclusion: Addition of patient-specific DIVA into the thermal modeling can significantly change predicted treatment quality. In cases where clinically detectable vessels pass the heated region, we advise to perform DIVA modeling.