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.

Radiofrequency applicator concepts for thermal magnetic resonance of brain tumors at 297 MHz (7.0 Tesla).

Purpose: Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. The annular phased array (APA) technique employing electromagnetic waves in the radiofrequency (RF) range allows for localized temperature increase in deep seated target volumes (TVs). Reports on clinical applications of the APA technique in the brain are still missing. Ultrahigh field magnetic resonance (MR) employs higher frequencies than conventional MR and has potential to provide focal temperature manipulation, high resolution imaging and noninvasive temperature monitoring using an integrated RF applicator (ThermalMR). This work examines the applicability of RF applicator concepts for ThermalMR of brain tumors at 297 MHz (7.0 Tesla).Methods: Electromagnetic field (EMF) simulations are performed for clinically realistic data based on GBM patients. Two algorithms are used for specific RF energy absorption rate based thermal intervention planning for small and large TVs in the brain, aiming at maximum RF power deposition or RF power uniformity in the TV for 10 RF applicator designs.Results: For both TVs , the power optimization outperformed the uniformity optimization. The best results for the small TV are obtained for the 16 element interleaved RF applicator using an elliptical antenna arrangement with water bolus. The two row elliptical RF applicator yielded the best result for the large TV.Discussion: This work investigates the capacity of ThermalMR to achieve targeted thermal interventions in model systems resembling human brain tissue and brain tumors.

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.

Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements.

Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

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.

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.

Patient-Specific Planning for Thermal Magnetic Resonance of Glioblastoma Multiforme.

Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. This drives research into optimization algorithms for treatment planning as well as radiofrequency (RF) applicator design for treatment delivery. In this work, nine clinically realistic GBM target volumes (TVs) for thermal intervention are compared using three optimization algorithms and up to ten RF applicator designs for thermal magnetic resonance. Hyperthermia treatment planning (HTP) was successfully performed for all cases, including very small, large, and even split target volumes. Minimum requirements formulated for the metrics assessing HTP outcome were met and exceeded for all patient specific cases. Results indicate a 16 channel two row arrangement to be most promising. HTP of TVs with a small extent in the cranial-caudal direction in conjunction with a large radial extent remains challenging despite the advanced optimization algorithms used. In general, deep seated targets are favorable. Overall, our findings indicate that a one-size-fits-all RF applicator might not be the ultimate approach in hyperthermia of brain tumors. It stands to reason that modular and reconfigurable RF applicator configurations might best suit the needs of targeting individual GBM geometry.

Salvage-Radiation Therapy and Regional Hyperthermia for Biochemically Recurrent Prostate Cancer after Radical Prostatectomy (Results of the Planned Interim Analysis).

Efforts to improve the outcome of prostate cancer (PC) patients after radical prostatectomy (RP) include adjuvant or salvage radiation therapy (SRT), but still up to 50% of patients develop a disease progression after radiotherapy (RT). Regional hyperthermia (HT) is well-known to improve tumor sensitivity to RT in several entities. Here we report on a planned interim analysis of tolerability and feasibility after recruitment of the first 50 patients of a trial combining SRT and HT. We conducted a prospective multicenter non-randomized Phase-II-Trial (HTProstate-NCT04159051) investigating the implementation of combined moderate-dose escalated SRT (70 Gy in 35 fractions) and locoregional deep HT (7-10 HT sessions). The primary endpoints were the rate of acute genitourinary (GU), gastrointestinal (GI), and HT-related toxicities, completed HT sessions (≥7), and SRT applications per protocol (≥95% of patients). The two-step design included a planned interim analysis for acute GU-, GI- and HT-specific toxicities to ensure patients' safety. Between November 2016 and December 2019, 52 patients entered into the trial. After 50 patients completed therapy and three months of follow-up, we performed the planned interim analysis. 10% of patients developed acute grade 2 GU and 4% grade 2 GI toxicities. No grade ≥3 GU or GI toxicities occurred. HT-specific symptoms grade 2 and 3 were observed in 4% and 2% of all patients. Thus, the pre-specified criteria for safety and continuation of recruitment were met. Moreover, ≥7 HT treatments were applicable, indicating the combination of SRT + HT to be feasible. Evaluation of early QoL showed no significant changes. With its observed low rate of GU and GI toxicities, moderate and manageable rates of HT-specific symptoms, and good feasibility, the combined SRT + HT seems to be a promising treatment approach for biochemical recurrence after RP in PC patients.

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.

Non-thermal effects of radiofrequency electromagnetic fields.

We explored the non-thermal effects of radiofrequency (RF) electromagnetic fields and established a theoretical framework to elucidate their electrophysiological mechanisms. In experiments, we used a preclinical treatment device to treat the human colon cancer cell lines HT-29 and SW480 with either water bath heating (WB-HT) or 13.56 MHz RF hyperthermia (RF-HT) at 42 °C for 60 min and analyzed the proliferation and clonogenicity. We elaborated an electrical model for cell membranes and ion channels and estimated the resulting ion fluxes. The results showed that, for both cell lines, using RF-HT significantly reduced proliferation and clonogenicity compared to WB-HT. According to our model, the RF electric field component was rectified and smoothed in the direction of the channel, which resulted in a DC voltage of ~ 1 µV. This may induce ion fluxes that can potentially cause relevant disequilibrium of most ions. Therefore, RF-HT creates additional non-thermal effects in association with significant ion fluxes. Increasing the understanding of these effects can help improve cancer therapy.

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.

Evaluation of MR-induced hot spots for different temporal SAR modes using a time-dependent finite difference method with explicit temperature gradient treatment.

An investigation of magnetic resonance (MR)-induced hot spots in a high-resolution human model is performed, motivated by safety aspects for the use of MR tomographs. The human model is placed in an MR whole body resonator that is driven in a quadrature excitation mode. The MR-induced hot spots are studied by varying the following: (1) the temporal specific absorption rate (SAR) mode ("steady imaging", "intermittent imaging"), (2) the simulation procedure (related to given power levels or to limiting temperatures), and (3) different thermal tissue properties including temperature-independent and temperature-dependent perfusion models. Both electromagnetic and thermodynamic simulations have been performed. For the electromagnetic modeling, a commercial finite-integration theory (FIT) code is applied. For the thermodynamic modeling, a time-domain finite-difference (FD) scheme is formulated that uses an explicit treatment of temperature gradient components. This allows a flux-vector-based implementation of heat transfer boundary conditions on cubical faces. It is shown that this FD scheme significantly reduces the staircase errors at thermal boundaries that are locally sloped or curved with respect to the cubical grid elements.

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.

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 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.