Regional hyperthermia for soft tissue sarcoma - a survey on current practice, controversies and consensus among 12 European centers.

PURPOSE: To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials. METHODS: In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT. RESULTS: We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40-43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry. DISCUSSION: There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects. CONCLUSIONS: The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.

Experimental and computational evaluation of capacitive hyperthermia.

OBJECTIVE: Hyperthermia as an enhancer of radio- and/or chemotherapy has been confirmed by various trials. Quite a few positive randomized trials have been carried out with capacitive hyperthermia systems (CHS), even though specific absorption rates (SAR) in deep regions are known to be inferior to the established annular-phased array techniques. Due to a lack of systematic SAR measurements for current capacitive technology, we performed phantom measurements in combination with simulation studies. MATERIALS AND METHODS: According to the current guidelines, homogeneous and inhomogeneous agarose phantoms were manufactured for the commercial CHS Celsius42. Temperature/time curves were registered, and specific absorption rate (SAR) profiles and distributions were derived using the temperature gradient method. We implemented models for electrodes and phantom setups for simulation studies using Sim4Life. RESULTS: For a standard total power of 200 W, we measured effective SAR until depths of 6-8 cm in a homogeneous phantom, which indicates fair heating conditions for tumor diseases in superficial and intermediate depths. A fat layer of 1 cm strongly weakens the SAR, but 10-20 W/kg are still achieved in intermediate to deep regions (2-10 cm). In the phantom setup with integrated bone, we measured low SAR of 5-10 W/kg in the cancellous bone. Our simulations could fairly describe the measured SAR distributions, but predict tendentially higher SAR than measured. Additional simulations suggest that we would achieve higher SAR with vital fatty tissue and bone metastases in clinical situations. CONCLUSION: Capacitive systems are suitable to heat superficial and medium-deep tumors as well as some bone metastases, and CHS application is feasible for a specific class of patients with pelvic and abdominal tumors. These findings are consistent with positive clinical studies.

Improved patient-specific hyperthermia planning based on parametrized electromagnetic and thermal models for the SIGMA-30 applicator.

OBJECTIVE: To create an improved planning method for pediatric regional hyperthermia (RHT) using the SIGMA-30 applicator (SIGMA-30). MATERIALS AND METHODS: An electromagnetic model of SIGMA-30 was generated for use with the finite-difference time-domain (FDTD) method. Applying special MATLAB-based algorithms, voxel models of a pediatric patient with pelvic rhabdomyosarcoma were created from Computed-Tomography (CT) contours for use with the FDTD method and the finite-difference (FD) method capable of using either temperature-independent or temperature-dependent perfusion models for solving the Bioheat Transfer Equation (BHTE). Patient models were parametrized regarding, first, the positioning in the applicator, second, the absorbed power range and, third, different perfusion models, resulting in the so-called Parametrized Treatment Models (PTMs). A novel dedicated optimization procedure was developed based on quantitative comparison of numerical calculations against temperature and power measurements from two RHT therapies. RESULTS: Using measured data, a realistic absorbed power range in the patient model was estimated. Within this range, several FDTD and BHTE runs were performed and, applying the aforementioned optimization scheme, the best PTMs and perfusion models were identified for each therapy via a retrospective comparison with measurements in 14 temperature sensor positions: 5 in the tumor, 8 in rectum and one in bladder. CONCLUSION: A novel dedicated optimization procedure for identification of suitable patient-specific electromagnetic and thermal models, which can be used for improved patient planning, was developed and evaluated by comparison with treatment-derived measurements using SIGMA-30. The optimization procedure can be extended to other hyperthermia applicators and to other patient types, including adults.

Temperatures in Pigs During 3 T MRI Temperatures, Heart Rates, and Breathing Rates of Pigs During RF Power Deposition in a 3 T (128 MHz) Body Coil.

Exposure to radiofrequency (RF) power deposition during magnetic resonance imaging (MRI) induces elevated body-tissue temperatures and may cause changes in heart and breathing rates, disturbing thermoregulation. Eleven temperature sensors were placed in muscle tissue and one sensor in the rectum (measured in 10 cm depth) of 20 free-breathing anesthetized pigs to verify temperature curves during RF exposure. Tissue temperatures and heart and breathing rates were measured before, during, and after RF exposure. Pigs were placed into a 60-cm diameter whole-body resonator of a 3 T MRI system. Nineteen anesthetized pigs were divided into four RF exposure groups: sham (0 W/kg), low-exposure (2.7 W/kg, mean exposure time 56 min), moderate-exposure (4.8 W/kg, mean exposure time 31 min), and high-exposure (4.4 W/kg, mean exposure time 61 min). One pig was exposed to a whole-body specific absorption rate (wbSAR) of 11.4 W/kg (extreme-exposure). Hotspot temperatures, measured by sensor 2, increased by mean 5.0 ± 0.9°C, min 3.9; max 6.3 (low), 7.0 ± 2.3°C, min 4.6; max 9.9 (moderate), and 9.2 ± 4.4°C, min 6.1, max 17.9 (high) compared with 0.3 ± 0.3°C in the sham-exposure group (min 0.1, max 0.6). Four time-temperature curves were identified: sinusoidal, parabolic, plateau, and linear. These curve shapes did not correlate with RF intensity, rectal temperature, breathing rate, or heart rate. In all pigs, rectal temperatures increased (2.1 ± 0.9°C) during and even after RF exposure, while hotspot temperatures decreased after exposure. When rectal temperature increased by 1°C, hotspot temperature increased up to 42.8°C within 37 min (low-exposure) or up to 43.8°C within 24 min (high-exposure). Global wbSAR did not correlate with maximum hotspot. Bioelectromagnetics. 2021;42:37-50. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.

Physical analysis of temperature-dependent effects of amplitude-modulated electromagnetic hyperthermia.

Purpose: Preclinical studies and clinical observations suggest that amplitude modulation (AM) below 100 kHz may enhance the intratumoral power absorption of radiofrequency hyperthermia at 13.56 MHz; however, it remains unclear whether AM induces temperature-dependent effects.Methods: We established tumor models assuming typical tumor architectures or cell suspensions to analyze the effects of additional power dissipation. The preconditions for demodulation at cell membranes in situ were outlined. The bioheat transfer equation was solved analytically for the selected models and the possibility of circumscribed temperature increases (point heating) with dependency on the specific absorption rate (SAR) peaks was estimated for centimeter down to nanometer scales.Results: Very-low-frequency (VLF) AM radiofrequency can increase the SAR in the extracellular space or necrosis of tumors as compared to radiofrequencies alone. Such modulation-derived SAR peaks can induce higher temperatures (hot spots) in tumors with necrotic areas of millimeter to centimeter size. However, for lesions <1 cm, excessive (unrealistic) SAR > 1000, 10,000 and 1014 W/kg for diameters of ∼5 mm, ∼1 mm and ∼10 nm (nanoheating), respectively, would be required to explain the cell kill observed in pre-clinical and clinical data, even with VLF modulation.Conclusion: Our analysis suggests that VLF AM of radiofrequency hyperthermia for a theoretical tumor model cannot induce relevant temperature-dependent effects, as the associated temperature increases caused by the resultant SAR peaks are too small. Further investigation of possible non-temperature-dependent effects is recommended.

Neoadjuvant chemotherapy plus radiation versus chemotherapy plus regional hyperthermia in high-grade soft tissue sarcomas: a retrospective comparison.

PURPOSE: Localized adult high-grade soft tissue sarcomas (STS) usually require multimodality treatment including surgery, radiotherapy, chemotherapy and hyperthermia. If maximal preoperative tumor-shrinkage is envisaged, neoadjuvant chemotherapy + radiation (CRT) is often applied, however at the expense of relatively high toxicities and increased postoperative complication rates. This study aims to compare preoperative CRT with neoadjuvant chemotherapy + regional hyperthermia (HCT) regarding histopathological response, toxicity and outcome. METHODS: In this retrospective analysis, 61 consecutive high-grade STS patients treated between 2009 and 2016 were included. All patients were treated within a prospective treatment protocol. 28 patients received neoadjuvant CRT 33 patients HCT. CRT consisted of four cycles doxorubicin/ifosfamide and two cycles ifosfamide concomitant to 50.4 Gray external beam radiotherapy. HCT consisted of 4-6 cycles doxorubicin/ifosfamide with deep regional hyperthermia administered bi-weekly during each cycle. Association of treatment modality with overall survival (OS), local control (LC) and freedom from distant metastases (FFDM) was evaluated by Kaplan-Meier and log-rank analyses. RESULTS: The overall patient characteristics were well balanced. Histopathological tumor response did not differ significantly between both groups (p = .67), neither did higher-grade toxicities during neoadjuvant treatment. Wound dehiscence (p = .018) and surgical hospital re-admissions (p < .001) were both significantly more frequent in the CRT group. Two-year OS, LC and FFDM rates of all patients were 93, 85 and 71% with no significant differences between CRT and HCT. CONCLUSION: Compared to CRT, HCT seems equally efficient and appears to bear less surgical complications. Interpretation should be cautious due to the low number of patients and the retrospective nature of this study.

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.

Regional hyperthermia of the abdomen, a pilot study towards the treatment of peritoneal carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis occurs in different cancer subtypes and is associated with a dismal prognosis. Some doubts remain whether the whole abdomen can be treated by regional hyperthermia, therefore we analyzed feasibility conducting a pilot study. METHODS: A simulation of the abdominopelvic heat distribution in 11 patients with peritoneal carcinomatosis was done using the HyperPlan software and the SIGMA-60 and SIGMA-Eye applicators. Tissue-specific region-related electrical and thermal parameters were used to solve the Maxwell's equations and the bioheat-transfer equation. Three-dimensional specific absorption rate (SAR) distributions and, additionally, estimated region-related perfusion rates were used to solve the bioheat-transfer equation. The predicted SAR and temperature distributions were compared with minimally invasive measurements in pelvic reference points. RESULTS: In 11 patients (7 of them treated in the SIGMA-60 and 4 in the SIGMA-Eye applicator) the measured treatment variables (SAR, temperatures in the pelvic reference points) indicated that the heated volumes were higher for the SIGMA-Eye applicator. The mean computed abdominal SARs were less for the SIGMA-Eye (33 versus 44 W/kg). Nevertheless, the temperature distributions in the abdomen (peritoneal cavity) were more homogeneous in the SIGMA-Eye applicator as compared to the SIGMA-60 as indicated by higher values of T90 (mean 40.2 versus 38.2 °C) and T50 (mean 41.1 versus 40.2 °C), while the maximum temperatures were similar (in the range 41 to 43 °C). Even though the mean abdominal SAR was lower in the SIGMA-Eye, the heat distribution covered a larger volume of the abdomen (in particular the upper abdomen). For the SIGMA-60 applicator the achieved T90 appeared to be limited between 41 and 42 °C, for the SIGMA Eye applicator more effective T90 in the range 42 to 43 °C were obtained. CONCLUSION: Our results suggest that an adequate heating of the abdomen and therefore abdominal regional hyperthermia in PC patients appears feasible. The SIGMA-Eye applicator appears to be superior compared to the SIGMA-60 applicator for abdominal hyperthermia.

Hyperthermia-related clinical trials on cancer treatment within the ClinicalTrials.gov registry.

PURPOSE: Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. MATERIALS AND METHODS: The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for hyperthermia or equivalent words. RESULTS: A total of 109 trials were identified in which hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleural n = 4, limb n = 2, hepatic n = 1). Sixteen trials (15%) were testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven trials (6%) superficial hyperthermia and two trials (2%) interstitial hyperthermia. One remaining trial tested laser hyperthermia. CONCLUSIONS: In contrast to the general opinion, this analysis shows continuous interest and ongoing clinical research in the field of hyperthermia. Interestingly, the majority of trials focused on some form of intraperitoneal hyperthermic chemoperfusion. Despite the high number of active clinical studies, HIPEC is a topic with limited attention at the annual meetings of the European Society for Hyperthermic Oncology and the Society of Thermal Medicine. The registration of on-going clinical trials is of paramount importance for the achievement of a comprehensive overview of available clinical research activities involving hyperthermia.

Experimental investigation and histopathological identification of acute thermal damage in skeletal porcine muscle in relation to whole-body SAR, maximum temperature, and CEM43 °C due to RF irradiation in an MR body coil of birdcage type at 123 MHz.

PURPOSE: This study is an investigation of the relationship between several characteristic parameters and acute thermal damage in porcine skeletal muscle. MATERIAL AND METHODS: Fourteen pigs under injection anaesthesia were placed into a magnetic resonance body coil and exposed for different time durations to different specific energy absorption rate (SAR) levels at 123 MHz. Local temperatures were measured using four temperature sensors. Sensors 1-3 were placed in skeletal muscle and one sensor was placed in the rectum. Sensors 1 and 2 were placed in hot-spot areas and sensor 3 was placed at the periphery of the animals. The pigs were exposed to whole-body SAR (SAR-wb) between 2.5 W/kg and 5.2 W/kg for 30 or 60 min. Three animals received no SAR. After each experiment, muscle samples adjacent to the positions of sensors 1-3 were taken for frozen section analysis. Three characteristic parameters were chosen for investigation: SAR-wb, maximum sensor temperature (T-max), and cumulative equivalent minutes at 43 °C (CEM43 °C). RESULTS: Histopathological criteria were established to detect acute thermal tissue damage in frozen sections such as widening of intercellular space between the muscle fibres and loss of glycogen. Clear tissue damage thresholds were found for T-max and CEM43 °C, though not for SAR-wb. For all animals with high thermal exposure, damage was also found for muscle samples adjacent to the peripheral sensor 3. CONCLUSIONS: Both T-max and CEM43, are able to predict thermal damage in porcine muscle. However, CEM43 is the less ambiguous parameter. The reasons for the occurrence of the aforementioned damage at low local temperatures at the animals' periphery remain unclear and further investigations are needed.

Non-invasive magnetic resonance thermography during regional hyperthermia.

Regional hyperthermia is a non-invasive technique in which cancer tissue is exposed to moderately high temperatures of approximately 43-45 degrees C. The clinical delivery of hyperthermia requires control of the temperatures applied. This is typically done using catheters with temperature probes, which is an interventional procedure. Additionally, a catheter allows temperature monitoring only at discrete positions. These limitations can be overcome by magnetic resonance (MR) thermometry, which allows non-invasive mapping of the entire treatment area during hyperthermia application. Various temperature-sensitive MRI parameters exist and can be exploited for MR temperature mapping. The most popular parameters are proton resonance frequency shift (PRFS) (Delta phi corresponding to a frequency shift of 0.011 ppm, i.e. 0.7 Hz per degrees C at 1.5 Tesla), diffusion coefficient D (Delta D/D = 2-3 % per degrees C), longitudinal relaxation time T(1) (Delta T1/T1 approximately 1% per degrees C), and equilibrium magnetisation M(0) (Delta M(0)/M=0.3% per degrees C). Additionally, MRI temperature mapping based on temperature-sensitive contrast media is applied. The different techniques of MRI thermometry were developed to serve different purposes. The PRFS method is the most sensitive proton imaging technique. A sensitivity of +/-0.5 degrees C is possible in vivo but use of PRFS imaging remains challenging because of a high sensitivity to susceptibility effects, especially when field homogeneity is poor, e.g. on interventional MR scanners or because of distortions caused by an inserted applicator. Diffusion-based MR temperature mapping has an excellent correlation with actual temperatures in tissues. Correct MR temperature measurement without rescaling is achieved using the T(1) method, if the scaling factor is known. MR temperature imaging methods using exogenous temperature indicators are chemical shift and 3D phase sensitive imaging. TmDOTMA(-) appears to be the most promising lanthanide complex because it showed a temperature imaging accuracy of <0.3 degrees C.

Implications of clinical RF hyperthermia on protection limits in the RF range.

The systemic temperature is meticulously regulated to 37-37.5 degrees C. Organ systems (skin, digestive system, muscles) have a considerable potential to regulate the perfusion for thermal regulation, physical activity, or digestion. While the regulation of the systemic temperature (37.5 degrees C) is quite strict, the tolerance and regulation potential with respect to local heat is more variable. Laboratory studies provided the relationship between thermal doses and cytotoxic effects. Tissue damage for short-term expositions (in the range of minutes) is only possible for temperatures above 50 degrees C. Radiofrequency radiation is utilized in cancer therapy, inducing local tissue temperatures in the range of 40-45 degrees C for 30-60 min. During local hyperthermia (with heated volumes <1 L) specific absorption rates (SARs) of 100-200 W kg, reactive perfusions of 20-40 mL/100 g/min, and tumor temperatures of 42-43 degrees C are achieved. Normally no side effects or damage in the normal tissue, such as muscle or skin, have been seen. During regional hyperthermia, SARs of 30-40 W kg are found in heated volumes of 10 L with temperatures of 41-42 degrees C in tumor-related measurement points. Then the reactive average perfusion is 6-9 mL/100 g/min (mean value 8 mL/100 g/min). Local temperatures even for higher SAR are regulated to values of not more than 40-42 degrees C. For these temperatures no damages in normal tissues have been found after regional hyperthermia in hundreds of patients. We conclude that the thermoregulatory potential for the whole body or large body regions is limited by the cardiac output, which can at least double the output from 5 to 10 L min. Even higher is the potential to compensate in smaller volumes. Here the perfusion in muscle can be increased from the basal value of 2-4 mL/100 g/min more than 5-10-fold.

Adaptation of antenna profiles for control of MR guided hyperthermia (HT) in a hybrid MR-HT system.

A combined numerical-experimental iterative procedure, based on the Gauss-Newton algorithm, has been developed for control of magnetic resonance (MR)-guided hyperthermia (HT) applications in a hybrid MR-HT system BSD 2000 3D-MRI. In this MR-HT system, composed of a 3-D HT applicator Sigma-Eye placed inside a tunnel-type MR tomograph Siemens MAGNETOM Symphony (1.5 T), the temperature rise due to the HT radiation can be measured on-line in three dimensions by use of the proton resonance frequency shift (PRFS) method. The basic idea of our iterative procedure is the improvement of the system's characterization by a step-by-step modification of the theoretical HT antenna profiles (electric fields radiated by single antennas). The adaptation of antenna profiles is efficient if the initial estimates are radiation fields calculated from a good a priori electromagnetic model. Throughout the iterative procedure, the calculated antenna fields (FDTD) are step-by-step modified by comparing the calculated and experimental data, the latter obtained using the PRFS method. The procedure has been experimentally tested on homogeneous and inhomogeneous phantoms. It is shown that only few comparison steps are necessary for obtaining a dramatic improvement of the general predictability and quality of the specific absorption rate (SAR) inside the MR-HT hybrid system.

Noninvasive magnetic resonance thermography of recurrent rectal carcinoma in a 1.5 Tesla hybrid system.

To implement noninvasive thermometry, we installed a hybrid system consisting of a radiofrequency multiantenna applicator (SIGMA-Eye) for deep hyperthermia (BSD-2000/3D) integrated into the gantry of a 1.5 Tesla magnetic resonance (MR) tomograph Symphony. This system can record MR data during radiofrequency heating and is suitable for application and evaluation of methods for MR thermography. In 15 patients with preirradiated pelvic rectal recurrences, we acquired phase data sets (25 slices) every 10 to 15 minutes over the treatment time (60-90 minutes) using gradient echo sequences (echo time = 20 ms), transformed the phase differences to MR temperatures, and fused the color-coded MR-temperature distributions with anatomic T1-weighted MR data sets. We could generate one complete series of MR data sets per patient with satisfactory quality for further analysis. In fat, muscle, water bolus, prostate, bladder, and tumor, we delineated regions of interest (ROI), used the fat ROI for drift correction by transforming these regions to a phase shift zero, and evaluated the MR-temperature frequency distributions. Mean MR temperatures (T(MR)), maximum T(MR), full width half maximum (FWHM), and other descriptors of tumors and normal tissues were noninvasively derived and their dependencies outlined. In 8 of 15 patients, direct temperature measurements in reference points were available. We correlated the tumor MR temperatures with direct measurements, clinical response, and tumor features (volume and location), and found reasonable trends and correlations. Therefore, the mean T(MR) of the tumor might be useful as a variable to evaluate the quality and effectivity of heat treatments, and consequently as optimization variable. Feasibility of noninvasive MR thermography for regional hyperthermia has been shown and should be further investigated.

A clinical water-coated antenna applicator for MR-controlled deep-body hyperthermia: a comparison of calculated and measured 3-D temperature data sets.

A magnetic resonance (MR)-compatible three-dimensional (3-D) hyperthermia applicator was developed and evaluated in the magnetic resonance (MR) tomograph Siemens MAGNETOM Symphony 1.5 T. Radiating elements of this applicator are 12 so-called water coated antenna (WACOA) modules, which are designed as specially shaped and adjustable dipole structures in hermetically closed cassettes that are filled by deionized water. The WACOA modules are arranged in the applicator frame in two transversal antenna subarrays, six antennas per subarray. As a standard load for the applicator an inhomogeneous phantom was fabricated. Details of applicator's realization are presented and a 3-D comparison of calculated and measured temperature data sets is made. A fair agreement is achieved that demonstrates the numerically supported applicator's ability of phase-defined 3-D pattern steering. Further refinement of numerical models and measuring methods is necessary. The applicator's design and the E-field calculations were performed using the finite-difference time-domain (FDTD) method. The calculation and optimization of temperature patterns was obtained using the finite element method (FEM). For MR temperature measurements the proton resonance frequency (PRF) method was used.

A practical approach to thermography in a hyperthermia/magnetic resonance hybrid system: validation in a heterogeneous phantom.

PURPOSE: This study investigates the feasibility and accuracy of noninvasive magnetic resonance (MR) monitoring for a system that includes a multiantenna applicator for part-body hyperthermia (SIGMA-Eye applicator, BSD-2000/3D) and a 1.5 Tesla MR tomograph (Siemens Magnetom Symphony). METHODS: A careful electrical decoupling enabled simultaneous operation of both systems, the hyperthermia system (100 MHz, up to 1600 W) and the MR tomograph (63.9 MHz). We used the phase data sets of a gradient echo sequence (long echo time TE = 20 ms) according to the proton frequency shift (PFS) method to determine MR temperature changes. Data postprocessing and visualization was conducted in the software platform AMIRA-HyperPlan. Heating was evaluated in an elliptical Lucite cylinder of 50 cm length filled with tissue-equivalent agarose and a skeleton made from low-dielectric material to simulate the heterogeneity of a real patient. Multiple catheters were included longitudinally for direct thermometry (using Bowman high-impedance thermistors). The phantom was positioned in the 24-antenna applicator SIGMA-Eye employing the integrated water bolus (filled with deionized water) both for coupling the radiated power into the lossy medium and to enable a correction procedure based on direct temperature measurements. RESULTS: In eight phantom experiments we monitored the heating in the applicator not only by repetitive acquisition of three-dimensional MR datasets, but also by measuring temperature-time curves directly at selected spatial positions. For the correction, we specified regions in the bolus. Direct bolus temperatures at fixed positions were taken to aim at best possible agreement between MR temperatures and these direct temperature-time curves. Then we compared additional direct temperature-position scans (thermal maps) for each experiment with the MR temperatures along these probes, which agreed satisfactorily (averaged accuracy of +/- 0.4-0.5 degrees C). The deviations decreased with decreasing observation time, temperature increase, and thermal load to the surroundings (corresponding to bolus heating)-estimating a resolution of, at best, +/- 0.2-0.3 degrees C. The acquired MR temperature distributions give also insight into limitations and control possibilities of regional hyperthermia (annular phased array technology) for various tumor sites. CONCLUSIONS: On-line MR monitoring of regional hyperthermia by using the PFS method is feasible in a phantom setup and can be further developed for clinical applications.

Development and evaluation of a three-dimensional hyperthermia applicator with Water-COated Antennas (WACOA).

A novel twelve-channel three-dimensional (3-D) hyperthermia applicator has been developed and evaluated, which consists of twelve separate WAter COated Antenna (WACOA) modules. The modules are arranged in three transversal antenna rings (sub-arrays) and are placed into an acrylic applicator frame as cartridge-like elements in a staggered arrangement. The operating frequency is 100 MHz. For the design of the applicator, the finite-difference time-domain (FDTD) method was used. The applicator's dimensions allow its placement into the gantry of a magnetic resonance (MR) tomograph. The WACOA modules are designed as MR-compatible specially shaped metallic cylindrical dipole structures that are placed into hermetically closed water-filled cassettes. Due to the design of the dipole structures, only a conventional coaxial feed circuitry is needed, and no external impedance matching networks are necessary. Instead, fine on-line impedance matching is realized using adjustable tuning rods and matching rings, both elements being parts of the radiating antenna structure. Experimental and numerical evaluations demonstrate a good stability of impedance matching, a low inter-channel coupling of less than -20 dB, and a good ability of field pattern steering.

Clinical use of the hyperthermia treatment planning system HyperPlan to predict effectiveness and toxicity.

PURPOSE: The main aim is to prove the clinical practicability of the hyperthermia treatment planning system HyperPlan on a beta-test level. Data and observations obtained from clinical hyperthermia are compared with the numeric methods FE (finite element) and FDTD (finite difference time domain), respectively. METHODS AND MATERIALS: The planning system HyperPlan is built on top of the modular, object-oriented platform for visualization and model generation AMIRA. This system already contains powerful algorithms for image processing, geometric modeling, and three-dimensional graphics display. A number of hyperthermia-specific modules are provided, enabling the creation of three-dimensional tetrahedral patient models suitable for treatment planning. Two numeric methods, FE and FDTD, are implemented in HyperPlan for solving Maxwell's equations. Both methods base their calculations on segmented (contour based) CT or MR image data. A tetrahedral grid is generated from the segmented tissue boundaries, consisting of approximately 80,000 tetrahedrons per patient. The FE method necessitates, primarily, this tetrahedral grid for the calculation of the E-field. The FDTD method, on the other hand, calculates the E-field on a cubical grid, but also requires a tetrahedral grid for correction at electrical interfaces. In both methods, temperature distributions are calculated on the tetrahedral grid by solving the bioheat transfer equation with the FE method. Segmentation, grid generation, E-field, and temperature calculation can be carried out in clinical practice at an acceptable time expenditure of about 1-2 days. RESULTS: All 30 patients we analyzed with cervical, rectal, and prostate carcinoma exhibit a good correlation between the model calculations and the attained clinical data regarding acute toxicity (hot spots), prediction of easy-to-heat or difficult-to-heat patients, and the dependency on various other individual parameters. We could show sufficient agreement between the calculations and measurements for power density (specific absorption rate) within the range of assessed precision. Tumor temperatures can only be estimated, because of the rather variable perfusion conditions. The results of the FE and FDTD methods are comparable, although slight differences exist resulting from the differences in the underlying models. There are also statistically provable differences among the tumor entities regarding the attained specific absorption rate, temperatures, and volume loads in normal tissue. However, gross fluctuations exist from patient to patient. CONCLUSION: The hyperthermia planning system HyperPlan could be validated for a number of the 30 patients. Further improvements in the implemented models, FE and FDTD, are required. Even at its present state of development, hyperthermia planning for regional hyperthermia delivers valuable information, not only for clinical practice, but also for further technologic improvements.

Experimental and numerical investigation of feed-point parameters in a 3-D hyperthermia applicator using different FDTD models of feed networks.

Experimental and numerical methods were used to determine the coupling of energy in a multichannel three-dimensional hyperthermia applicator (SIGMA-Eye), consisting of 12 short dipole antenna pairs with stubs for impedance matching. The relationship between the amplitudes and phases of the forward waves from the amplifiers, to the resulting amplitudes and phases at the antenna feed-points was determined in terms of interaction matrices. Three measuring methods were used: 1) a differential probe soldered directly at the antenna feed-points; 2) an E-field sensor placed near the feed-points; and 3) measurements were made at the outputs of the amplifier. The measured data were compared with finite-difference time-domain (FDTD) calculations made with three different models. The first model assumes that single antennas are fed independently. The second model simulates antenna pairs connected to the transmission lines. The measured data correlate best with the latter FDTD model, resulting in an improvement of more than 20% and 20 degrees (average difference in amplitudes and phases) when compared with the two simpler FDTD models.