Abstract
BackgroundGlioblastoma 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.MethodsA 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.ResultsThe 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.ConclusionThe 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.
Highlights
Glioblastoma multiforme is the most common and most aggressive malign brain tumor
A temperature of >7 °C in the vicinity of the phantom could be reached for an radio frequency (RF) heating duration of 2 min. e-f Thermal simulations in human voxel model “Ella” [27] in order to demonstrate the capabilities of the applicator to generate a hotspot in (e) the center of the brain and (f) the periphery applying the same phase setting as in (d) and in the vicinity (Fig. 3f ) of the human brain
Electromagnetic field (EMF) simulations and experiments demonstrate the feasibility of an 8-channel applicator for magnetic resonance (MR) imaging, MR thermometry and controlled targeted RF heating at 7.0 T
Summary
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. Despite demarcation in computed tomography (CT) or magnetic resonance imaging (MRI) glioblastoma multiforme presents no clear microscopic barriers towards the unaffected brain [1] This pathology makes a complete surgical resection challenging if not elusive. Interstitial hyperthermia in addition to external beam radiation therapy and brachytherapy of the brain has been demonstrated to improve survival in a randomized trial [6]. This type of treatment is not applicable to all tumor locations within the brain, and did not become accepted in clinical practice due to its invasive nature
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