Assessment of the thermal tissue models for the head and neck hyperthermia treatment planning.

PURPOSE: To compare different thermal tissue models for head and neck hyperthermia treatment planning, and to assess the results using predicted and measured applied power data from clinical treatments. METHODS: Three commonly used temperature models from literature were analysed: "constant baseline", "constant thermal stress" and "temperature dependent". Power and phase data of 93 treatments of 20 head and neck patients treated with the HYPERcollar3D applicator were used. The impact on predicted median temperature T50 inside the target region was analysed with maximum allowed temperature of 44 °C in healthy tissue. The robustness of predicted T50 for the three models against the influence of blood perfusion, thermal conductivity and the assumed hotspot temperature level was analysed. RESULTS: We found an average predicted T50 of 41.0 ± 1.3 °C (constant baseline model), 39.9 ± 1.1 °C (constant thermal stress model) and 41.7 ± 1.1 °C (temperature dependent model). The constant thermal stress model resulted in the best agreement between the predicted power (P = 132.7 ± 45.9 W) and the average power measured during the hyperthermia treatments (P = 129.1 ± 83.0 W). CONCLUSION: The temperature dependent model predicts an unrealistically high T50. The power values for the constant thermal stress model, after scaling simulated maximum temperatures to 44 °C, matched best to the average measured powers. We consider this model to be the most appropriate for temperature predictions using the HYPERcollar3D applicator, however further studies are necessary for developing of robust temperature model for tissues during heat stress.

On the Role of Training Data for SVM-Based Microwave Brain Stroke Detection and Classification.

The aim of this work was to test microwave brain stroke detection and classification using support vector machines (SVMs). We tested how the nature and variability of training data and system parameters impact the achieved classification accuracy. Using experimentally verified numerical models, a large database of synthetic training and test data was created. The models consist of an antenna array surrounding reconfigurable geometrically and dielectrically realistic human head phantoms with virtually inserted strokes of arbitrary size, and different dielectric parameters in different positions. The generated synthetic data sets were used to test four different hypotheses, regarding the appropriate parameters of the training dataset, the appropriate frequency range and the number of frequency points, as well as the level of subject variability to reach the highest SVM classification accuracy. The results indicate that the SVM algorithm is able to detect the presence of the stroke and classify it (i.e., ischemic or hemorrhagic) even when trained with single-frequency data. Moreover, it is shown that data of subjects with smaller strokes appear to be the most suitable for training accurate SVM predictors with high generalization capabilities. Finally, the datasets created for this study are made available to the community for testing and developing their own algorithms.

Microwave Catheter Navigation System for the Radiofrequency Liver Ablation.

Thermal ablation is a well-known method used in interventional radiology to treat cancer. The treatment success is closely related to the exact catheter location in the treated area. Current navigation methods are based mostly on ultrasound or computed tomography. This work explores the possibility of tracking the catheter position during ablation treatment of hepatocellular carcinomas (HCC) using an ultra-wideband (UWB) antenna array and microwave radar imaging based on the "Delay and Sum" (DAS) algorithm. The feasibility was first numerically studied on a simple homogeneous liver model. A heterogeneous anthropomorphic 3D model of the treated region consisting of the main organs within the treated area was then used. Various standard radiofrequency ablation (RFA) catheters were placed virtually in the heterogeneous model. The location and orientation of the antenna elements of the developed imaging system and the applied frequency band were studied. Subsequently, an experimental setup consisting of a 3D printed homogeneous anthropomorphic model, eight UWB dipole antennas, and catheters was created and used in a series of measurements. The average accuracy determining the catheter position from simulated and experimental data was 3.88 ± 0.19 and 6.13 ± 0.66 mm, which are close to the accuracy of clinical navigation systems.

Microwave Hyperthermia of Brain Tumors: A 2D Assessment Parametric Numerical Study.

Due to the clinically proven benefit of hyperthermia treatments if added to standard cancer therapies for various tumor sites and the recent development of non-invasive temperature measurements using magnetic resonance systems, the hyperthermia community is convinced that it is a time when even patients with brain tumors could benefit from regional microwave hyperthermia, even if they are the subject of a treatment to a vital organ. The purpose of this study was to numerically analyze the ability to achieve a therapeutically relevant constructive superposition of electromagnetic (EM) waves in the treatment of hyperthermia targets within the brain. We evaluated the effect of the target size and position, operating frequency, and the number of antenna elements forming the phased array applicator on the treatment quality. In total, 10 anatomically realistic 2D human head models were considered, in which 10 circular hyperthermia targets with diameters of 20, 25, and 30 mm were examined. Additionally, applicators with 8, 12, 16, and 24 antenna elements and operating frequencies of 434, 650, 915, and 1150 MHz, respectively, were analyzed. For all scenarios considered (4800 combinations), the EM field distributions of individual antenna elements were calculated and treatment planning was performed. Their quality was evaluated using parameters applied in clinical practice, i.e., target coverage (TC) and the target to hot-spot quotient (THQ). The 12-antenna phased array system operating at 434 MHz was the best candidate among all tested systems for HT treatments of glioblastoma tumors. The 12 antenna elements met all the requirements to cover the entire target area; an additional increase in the number of antenna elements did not have a significant effect on the treatment quality.

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.

A Guide for Water Bolus Temperature Selection for Semi-Deep Head and Neck Hyperthermia Treatments Using the HYPERcollar3D Applicator.

During hyperthermia cancer treatments, especially in semi-deep hyperthermia in the head and neck (H&N) region, the induced temperature pattern is the result of a complex interplay between energy delivery and tissue cooling. The purpose of this study was to establish a water bolus temperature guide for the HYPERcollar3D H&N applicator. First, we measured the HYPERcollar3D water bolus heat-transfer coefficient. Then, for 20 H&N patients and phase/amplitude settings of 93 treatments we predict the T50 for nine heat-transfer coefficients and ten water bolus temperatures ranging from 20-42.5 °C. Total power was always tuned to obtain a maximum of 44 °C in healthy tissue in all simulations. As a sensitivity study we used constant and temperature-dependent tissue cooling properties. We measured a mean heat-transfer coefficient of h = 292 W m-2K-1 for the HYPERcollar3D water bolus. The predicted T50 shows that temperature coverage is more sensitive to the water bolus temperature than to the heat-transfer coefficient. We propose changing the water bolus temperature from 30 °C to 35 °C which leads to a predicted T50 increase of +0.17/+0.55 °C (constant/temperature-dependent) for targets with a median depth < 20 mm from the skin surface. For deeper targets, maintaining a water bolus temperature at 30 °C is proposed.

Experimental Validation of the MRcollar: An MR Compatible Applicator for Deep Heating in the Head and Neck Region.

Clinical effectiveness of hyperthermia treatments, in which tumor tissue is artificially heated to 40-44 °C for 60-90 min, can be hampered by a lack of accurate temperature monitoring. The need for noninvasive temperature monitoring in the head and neck region (H&N) and the potential of MR thermometry prompt us to design an MR compatible hyperthermia applicator: the MRcollar. In this work, we validate the design, numerical model, and MR performance of the MRcollar. The MRcollar antennas have low reflection coefficients (<-15 dB) and the intended low interaction between the individual antenna modules (<-32 dB). A 10 °C increase in 3 min was reached in a muscle-equivalent phantom, such that the specifications from the European Society for Hyperthermic Oncology were easily reached. The MRcollar had a minimal effect on MR image quality and a five-fold improvement in SNR was achieved using the integrated coils of the MRcollar, compared to the body coil. The feasibility of using the MRcollar in an MR environment was shown by a synchronous heating experiment. The match between the predicted SAR and measured SAR using MR thermometry satisfied the gamma criteria [distance-to-agreement = 5 mm, dose-difference = 7%]. All experiments combined show that the MRcollar delivers on the needs for MR-hyperthermia in the H&N and is ready for in vivo investigation.

Feasibility Evaluation of Metamaterial Microwave Sensors for Non-Invasive Blood Glucose Monitoring.

The use of microwave technology is currently under investigation for non-invasive estimation of glycemia in patients with diabetes. Due to their construction, metamaterial (MTM)-based sensors have the potential to provide higher sensitivity of the phase shift of the S21 parameter (∠S21) to changes in glucose concentration compared to standard microstrip transmission line (MSTL)-based sensors. In this study, a MSTL sensor and three MTM sensors with 5, 7, and 9 MTM unit cells are exposed to liquid phantoms with different dielectric properties mimicking a change in blood glucose concentration from 0 to 14 mmol/L. Numerical models were created for the individual experiments, and the calculated S-parameters show good agreement with experimental results, expressed by the maximum relative error of 8.89% and 0.96% at a frequency of 1.99 GHz for MSTL and MTM sensor with nine unit cells, respectively. MTM sensors with an increasing number of cells show higher sensitivity of 0.62° per mmol/L and unit cell to blood glucose concentration as measured by changes in ∠S21. In accordance with the numerical simulations, the MTM sensor with nine unit cells showed the highest sensitivity of the sensors proposed by us, with an average of 3.66° per mmol/L at a frequency of 1.99 GHz, compared to only 0.48° per mmol/L for the MSTL sensor. The multi-cell MTM sensor has the potential to proceed with evaluation of human blood samples.

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.

Impact of Number of Segmented Tissues on SAR Prediction Accuracy in Deep Pelvic Hyperthermia Treatment Planning.

In hyperthermia, the general opinion is that pre-treatment optimization of treatment settings requires a patient-specific model. For deep pelvic hyperthermia treatment planning (HTP), tissue models comprising four tissue categories are currently discriminated. For head and neck HTP, we found that more tissues are required for increasing accuracy. In this work, we evaluated the impact of the number of segmented tissues on the predicted specific absorption rate (SAR) for the pelvic region. Highly detailed anatomical models of five healthy volunteers were selected from a virtual database. For each model, seven lists with varying levels of segmentation detail were defined and used as an input for a modeling study. SAR changes were quantified using the change in target-to-hotspot-quotient and maximum SAR relative differences, with respect to the most detailed patient model. The main finding of this study was that the inclusion of high water content tissues in the segmentation may result in a clinically relevant impact on the SAR distribution and on the predicted hyperthermia treatment quality when considering our pre-established thresholds. In general, our results underline the current clinical segmentation protocol and help to prioritize any improvements.

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.

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.

Predictive value of SAR based quality indicators for head and neck hyperthermia treatment quality.

PURPOSE: Hyperthermia treatment quality determines treatment effectiveness as shown by the clinically derived thermal-dose effect relations. SAR based optimization factors are used as possible surrogate for temperature, since they are not affected by thermal tissue properties uncertainty and variations. Previously, target coverage (TC) at the 25% and 50% iso-SAR level was shown predictive for treatment outcome in superficial hyperthermia and the target-to-hot-spot-quotient (THQ) was shown to highly correlate with predictive temperature in deep pelvic hyperthermia. Here, we investigate the correlation with temperature for THQ and TC using an 'intermediate' scenario: semi-deep hyperthermia in the head & neck region using the HYPERcollar3D. METHODS: Fifteen patient-specific models and two different planning approaches were used, including random perturbations to circumvent optimization bias. The predicted SAR indicators were compared to predicted target temperature distribution indicators T50 and T90, i.e., the median and 90th percentile temperature respectively. RESULTS: The intra-patient analysis identified THQ, TC25 and TC50 as good temperature surrogates: with a mean correlation coefficient R2T50 = 0.72 and R2T90=0.66. The inter-patient analysis identified the highest correlation with TC25 (R2T50 = 0.76, R2T90=0.54) and TC50 (R2T50 = 0.74, R2T90 = 0.56). CONCLUSION: Our investigation confirmed the validity of our current strategy for deep hyperthermia in the head & neck based on a combination of THQ and TC25. TC50 was identified as the best surrogate since it enables optimization and patient inclusion decision making using one single parameter.

Hyperthermia treatment planning guided applicator selection for sub-superficial head and neck tumors heating.

PURPOSE: In this study, we investigated the differences in hyperthermia treatment (HT) quality between treatments applied with different hyperthermia systems for sub-superficial tumours in the head and neck (H&N) region. MATERIALS AND METHODS: In 24 patients, with a clinical target volume (CTV) extending up to 6 cm from the surface, we retrospectively analysed the predicted HT quality achievable by two planar applicator arrays or one phased-array hyperthermia system. Hereto, we calculated and compared the specific absorption rate (SAR) and temperature distribution coverage of the CTV and gross tumour volume (GTV) for the Lucite cone applicator (LCA: planar), current sheet applicator (CSA: planar) and the HYPERcollar (phased-array). RESULTS: The HYPERcollar provides better SAR coverage than planar applicators if the target region is fully enclosed by its applicator frame. For targets extending outside the HYPERcollar frame, sufficient SAR coverage (25% target coverage, i.e. TC25 ≥ 75%) can still be achieved using the LCA when the target is fully under the LCA aperture and not deeper than 50 mm from the patient surface. CONCLUSION: Simulations predict that the HYPERcollar (hence also its successor the HYPERcollar3D) is to be preferred over planar applicators such as LCA and current sheet applicator in sub-superficial tumours in the H&N region when used within specifications.

Impact of silicone and metal port-a-cath implants on superficial hyperthermia treatment quality.

PURPOSE: A port-a-cath is a device implanted under the skin for continuous drug administration. It is composed of a catheter and a silicone or metal reservoir. A simulation study was done to assess the impact of a port-a-cath implant on the quality of superficial hyperthermia treatments applied using the Lucite cone applicator (LCA). METHODS: Specific absorption rate (SAR) and temperature distributions were predicted using SEMCAD-X (version 14.8). We simulated 72 arrangements: two LCA-implant set-ups (central port-a-cath or at an edge below the LCA footprint), six translations of the LCA per set-up, two LCA orientations (Parallel or perpendicular electric field direction) per set-up, two implant materials (silicon or metal) and a control without port-a-cath. Treatment quality was quantified by the average 1 g SAR coverage (CV25%), i.e. volume within the 25% iso-SAR surface, and the volume within the 40 °C iso-temperature surface (CV40 °C). RESULTS: CV25% reduced with a silicon port-a-cath located below the LCA footprint. In the worst scenario, only 64% of the CV25% of the control set-up was achieved. For a metal port-a-cath below the LCA aperture, dramatic reductions of CV25% were predicted: worst scenario down to 12.1% of the control CV25%. For the CV40 °C the worst case values were 74.5% and 6.5%, for silicon and metal implants, respectively. CONCLUSIONS: A silicone port-a-cath below the LCA had a smaller effect on treatment quality than a metal implant. Based on this study we recommend verifying heating quality by 3D patient-specific treatment planning when a port-a-cath is located below the footprint of the applicator.

Procedure for creating a three-dimensional (3D) model for superficial hyperthermia treatment planning.

PURPOSE: To make a patient- and treatment-specific computed tomography (CT) scan and to create a three-dimensional (3D) patient model for superficial hyperthermia treatment planning (SHTP). PATIENTS, MATERIALS, AND METHODS: Patients with recurrent breast adenocarcinoma in previously irradiated areas referred for radiotherapy (RT) and hyperthermia (HT) treatment and giving informed consent were included. After insertion of the thermometry catheters in the treatment area, a CT scan in the treatment position was made. RESULTS: A total of 26 patients have been, thus far, included in the study. During the study period, five types of adjustments were made to the procedure: (1) marking the RT field with radioopaque markers, (2) making the CT scan after the first HT treatment instead of before, (3) using an air- and foam-filled (dummy) water bolus, (4) a change to radiolucent catheters for which radioopaque markers were needed, and (5) marking the visible/palpable extent of the tumor with radioopaque markers, if necessary. With these adjustments, all necessary information is visible on the CT scan. Each CT slice was automatically segmented into muscle, fat, bone, and air. RT field, catheters, applicators, and tumor lesions, if indicated, were outlined manually using the segmentation program iSeg. Next the model was imported into SEMCAD X, a 3D electromagnetic field simulator. CONCLUSION: Using the final procedure to obtain a patient- and treatment-specific CT scan, it is possible to create a 3D model for SHTP.