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Purpose: Mild hyperthermia can be used as an adjuvant therapy to enhance radiation therapy or chemotherapy of cancer. However, administering mild hyperthermia is technically challenging due to the high accuracy required of the temperature control. MR guided high-intensity focused ultrasound (MR-HIFU) is a technology that can address this challenge. In this work, accurate and spatially uniform mild hyperthermia is demonstrated for deep-seated clinically relevant heating volumes using a HIFU system under MR guidance. Methods: Mild hyperthermia heating was evaluated for temperature accuracy and spatial uniformity in 11 in vivo porcine leg experiments. Hyperthermia was induced with a commercial Philips Sonalleve MR-HIFU system embedded in a 1.5T Ingenia MR scanner. The operating software was modified to allow extended duration mild hyperthermia. Heating time varied from 10 min up to 60 min and the assigned target temperature was 42.5• C. Electronic focal point steering, mechanical transducer movement, and dynamic transducer element switch-off were exploited to enlarge the heated volume and obtain uniform heating throughout the acoustic beam path. Multiple temperature mapping images were used to control and monitor the heating. The magnetic field drift and transducer susceptibility artifacts were compensated to enable accurate volumetric MR thermometry. Results: The obtained mean temperature for the target area (the cross sectional area of the heated volume at focal depth primarily used to control the heating) was on average 42.0 ± 0.6• C. Temperature uniformity in the target area was evaluated using T10 and T90, which were 43.1 ± 0.6 and 40.9 ± 0.6• C, respectively. For the near field, the corresponding temperatures were 39.3 ± 0.8• C (average), 40.6 ± 1.0• C (T10), and 38.0 ± 0.9• C (T90). The sonications resulted in a concise heating volume, typically in the shape of a truncated cone. The average depth reached from the skin was 86.9 mm. The results show that the heating algorithm was able to induce deep heating while keeping the near-field temperature uniform and at a safe level. Conclusions: The capability of MR-HIFU to induce accurate, spatially uniform, and robust mild hyperthermia in large deep-seated volumes was successfully demonstrated through a series of in vivo animal experiments. C

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Focused ultrasound is very well suited for inducing noninvasive local hyperthermia. Since magnetic resonance imaging (MRI) may be employed to obtain real-time temperature maps noninvasively the combination of these two technologies offers great advantages specifically aimed toward oncological studies. Real-time identification of the target region and accurate control of the temperature evolution during the treatment has now become possible. Thermal ablation of pathological tissue, local drug delivery using thermosensitive micro-carriers and controlled transgene expression using thermosensitive promoters have recently been demonstrated with this unique technology. Based on these experiments combined focused ultrasound and MRI thermometry holds promise for future oncological diagnostics and treatment. In this paper, we review some of the recent methodological developments as well as experimental and first clinical studies using this approach.