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Glioblastoma multiforme is the most frequent and most aggressive malignant brain tumor with de facto no long term curation by the use of current multimodal therapeutic approaches. The efficacy of brachytherapy and enhancing interstitial hyperthermia has been demonstrated. RF heating at ultrahigh fields (B0=7.0T, f=298MHz) has the potential of delivering sufficiently large thermal dosage for hyperthermia of relatively large tumor areas. This work focuses on electromagnetic field (EMF) simulations and provides realistic applicator designs tailored for simultaneous RF heating and MRI. Our simulations took advantage of target volumes derived from patient data, and our preliminary results suggest that RF power can be focused to both a small tumor area and a large clinical target volume.

Clinically established thermal therapies such as thermoablative approaches or adjuvant hyperthermia treatment rely on accurate thermal dose information for the evaluation and adaptation of the thermal therapy. Intratumoural temperature measurements have been correlated successfully with clinical end points. Magnetic resonance imaging is the most suitable technique for non-invasive thermometry avoiding complications related to invasive temperature measurements. Since the advent of MR thermometry two decades ago, numerous MR thermometry techniques have been developed, continuously increasing accuracy and robustness forin vivoapplications. While this progress was primarily focused on relative temperature mapping, current and future efforts will likely close the gap towards quantitative temperature readings. These efforts are essential to benchmark thermal therapy efficiency, to understand temperature-related biophysical and physiological processes and to use these insights to set new landmarks for diagnostic and therapeutic applications. With that in mind, this review summarises and discusses advances in MR thermometry, providing practical considerations, pitfalls and technical obstacles constraining temperature measurement accuracy, spatial and temporal resolutionin vivo. Established approaches and current trends in thermal therapy hardware are surveyed with respect to potential benefits for MR thermometry. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme is the most common and most aggressive malign brain tumor. The 5-year survival rate after tumor resection and adjuvant chemoradiation is only 10 %, with almost all recurrences occurring in the initially treated site. Attempts to improve local control using a higher radiation dose were not successful so that alternative additive treatments are urgently needed. Given the strong rationale for hyperthermia as part of a multimodal treatment for patients with glioblastoma, non-invasive radio frequency (RF) hyperthermia might significantly improve treatment results.Methods: A non-invasive applicator was constructed utilizing the magnetic resonance (MR) spin excitation frequency for controlled RF hyperthermia and MR imaging in an integrated system, which we refer to as thermal MR. Applicator designs at RF frequencies 300 MHz, 500 MHz and 1GHz were investigated and examined for absolute applicable thermal dose and temperature hotspot size. Electromagnetic field (EMF) and temperature simulations were performed in human voxel models. RF heating experiments were conducted at 300 MHz and 500 MHz to characterize the applicator performance and validate the simulations.Results: The feasibility of thermal MR was demonstrated at 7.0 T. The temperature could be increased by ~11 °C in 3 min in the center of a head sized phantom. Modification of the RF phases allowed steering of a temperature hotspot to a deliberately selected location. RF heating was monitored using the integrated system for MR thermometry and high spatial resolution MRI. EMF and thermal simulations demonstrated that local RF hyperthermia using the integrated system is feasible to reach a maximum temperature in the center of the human brain of 46.8 °C after 3 min of RF heating while surface temperatures stayed below 41 °C. Using higher RF frequencies reduces the size of the temperature hotspot significantly.Conclusion: The opportunities and capabilities of thermal magnetic resonance for RF hyperthermia interventions of intracranial lesions are intriguing. Employing such systems as an alternative additive treatment for glioblastoma multiforme might be able to improve local control by "fighting fire with fire". Interventions are not limited to the human brain and might include temperature driven targeted drug and MR contrast agent delivery and help to understand temperature dependent bio- and physiological processes in-vivo. [ABSTRACT FROM AUTHOR]

Thermal Magnetic Resonance (ThermalMR) leverages radio frequency (RF)-induced heating to examine the role of temperature in biological systems and disease. To advance RF heating with multi-channel RF antenna arrays and overcome the shortcomings of current RF signal sources, this work reports on a 32-channel modular signal generator (SGPLL). The SGPLL was designed around phase-locked loop (PLL) chips and a field-programmable gate array chip. To examine the system properties, switching/settling times, accuracy of RF power level and phase shifting were characterized. Electric field manipulation was successfully demonstrated in deionized water. RF heating was conducted in a phantom setup using self-grounded bow-tie RF antennae driven by the SGPLL. Commercial signal generators limited to a lower number of RF channels were used for comparison. RF heating was evaluated with numerical temperature simulations and experimentally validated with MR thermometry. Numerical temperature simulations and heating experiments controlled by the SGPLL revealed the same RF interference patterns. Upon RF heating similar temperature changes across the phantom were observed for the SGPLL and for the commercial devices. To conclude, this work presents the first 32-channel modular signal source for RF heating. The large number of coherent RF channels, wide frequency range and accurate phase shift provided by the SGPLL form a technological basis for ThermalMR controlled hyperthermia anti-cancer treatment. [ABSTRACT FROM AUTHOR]

Thermal magnetic resonance (ThermalMR) accommodates radio frequency (RF)-induced temperature modulation, thermometry, anatomic and functional imaging, and (nano)molecular probing in an integrated RF applicator. This study examines the feasibility of ThermalMR for the controlled release of a model therapeutics from thermoresponsive nanogels using a 7.0-tesla whole-body MR scanner en route to local drug-delivery-based anticancer treatments. The capacity of ThermalMR is demonstrated in a model system involving the release of fluorescein-labeled bovine serum albumin (BSA-FITC, a model therapeutic) from nanometer-scale polymeric networks. These networks contain thermoresponsive polymers that bestow environmental responsiveness to physiologically relevant changes in temperature. The release profile obtained for the reference data derived from a water bath setup used for temperature stimulation is in accordance with the release kinetics deduced from the ThermalMR setup. In conclusion, ThermalMR adds a thermal intervention dimension to an MRI device and provides an ideal testbed for the study of the temperature-induced release of drugs, magnetic resonance (MR) probes, and other agents from thermoresponsive carriers. Integrating diagnostic imaging, temperature intervention, and temperature response control, ThermalMR is conceptually appealing for the study of the role of temperature in biology and disease and for the pursuit of personalized therapeutic drug delivery approaches for better patient care. [ABSTRACT FROM AUTHOR]