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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Purpose: Ablative hyperthermia (>55• C) has been used as a definitive treatment for accessible solid tumors not amenable to surgery, whereas mild hyperthermia (40-45• C) has been shown effective as an adjuvant for both radiotherapy and chemotherapy. An optimal mild hyperthermia treatment is spatially accurate, with precise and homogeneous heating limited to the target region while also limiting the likelihood of unwanted thermal or mechanical bioeffects (tissue damage, vascular shutoff). Magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) can noninvasively heat solid tumors under image-guidance. In a mild hyperthermia setting, a sonication approach utilizing multiple concurrent foci may provide the benefit of reducing acoustic pressure in the focal region (leading to reduced or no mechanical effects), while providing better control over the heating. The objective of this study was to design, implement, and characterize a multifoci sonication approach in combination with a mild hyperthermia heating algorithm, and compare it to the more conventional method of electronically sweeping a single focus. Methods: Simulations (acoustic and thermal) and measurements (acoustic, with needle hydrophone) were performed. In addition, heating performance of multifoci and single focus sonications was compared using a clinical MR-HIFU platform in a phantom (target = 4-16 mm), in normal rabbit thigh muscle (target = 8 mm), and in a Vx2 tumor (target = 8 mm). A binary control algorithm was used for real-time mild hyperthermia feedback control (target range = 40.5-41• C). Data were analyzed for peak acoustic pressure and intensity, heating energy efficiency, temperature accuracy (mean), homogeneity of heating (standard deviation [SD], T10 and T90), diameter and length of the heated region, and thermal dose (CEM 43 ). Results: Compared to the single focus approach, multifoci sonications showed significantly lower (67% reduction) peak acoustic pressures in simulations and hydrophone measurements. In a rabbit Vx2 tumor, both single focus and multifoci heating approaches were accurate (mean = 40.82±0.12• C [single] and 40.70±0.09) and precise (standard deviation = 0.65±0.05• C [single] and 0.64±0.04, producing homogeneous heating (T 10-90 = 1.62• C [single] and 1.41. Heated regions were significantly shorter in the beam path direction (35% reduction, p < 0.05, Tukey) for multifoci sonications, i.e., resulting in an aspect ratio closer to one. Energy efficiency was lower for the multifoci approach. Similar results were achieved in phantom and rabbit muscle heating experiments. Conclusions: A multifoci sonication approach was combined with a mild hyperthermia heating algorithm, and implemented on a clinical MR-HIFU platform. This approach resulted in accurate and precise heating within the targeted region with significantly lower acoustic pressures and spatially more confined heating in the beam path direction compared to the single focus sonication method. The reduction in acoustic pressure and improvement in sp...

There is growing interest in performing hyperthermia treatments with clinical MRI-guided high-intensity focused ultrasound (MR-HIFU) therapy systems designed for tissue ablation. During hyperthermia treatment, however, due to the narrow therapeutic window (41–45°C), careful evaluation of the accuracy of PRF shift MR thermometry for these types of exposures is required. Purpose The purpose of this study was to evaluate the accuracy of MR thermometry using a clinical MR-HIFU system equipped with hyperthermia treatment algorithm. Methods Mild heating was performed in a tissue-mimicking phantom with implanted temperature sensors using the clinical MR-HIFU system. The influence of image-acquisition settings and post-acquisition correction algorithms on the accuracy of temperature measurements was investigated. The ability to achieve uniform heating for up to 40 minutes was evaluated in rabbit experiments. Results Automatic center-frequency adjustments prior to image-acquisition corrected the image-shifts on the order of 0.1 mm/min. Zero and first order phase variations were observed over time, supporting the use of a combined drift correction algorithm. The temperature accuracy achieved using both center-frequency adjustment and the combined drift correction algorithm was 0.57 ± 0.58 °C in heated region and 0.54 ± 0.42 °C in unheated region. Conclusion Accurate temperature monitoring of hyperthermia exposures using PRF shift MR thermometry is possible through careful implementation of image-acquisition settings and drift correction algorithms. For the evaluated clinical MR-HIFU system, center-frequency adjustment eliminated image-shifts, and a combined drift correction algorithm achieved temperature measurements with an acceptable accuracy for monitoring and controlling hyperthermia exposures.

Since the proposed refocusing algorithm is compatible with a standard interventional preplanning and requires only a minimal amount of processing, it presents a promising approach to compensate for aberration in heterogeneous tissues such as the human breast.