Background: Magnetic resonance guided focused ultrasound was suggested for the induction of deep localized hyperthermia adjuvant to radiation- or chemotherapy. In this study we are aiming to validate an experimental model for the induction of uniform temperature elevation in osteolytic bone tumours, using the natural acoustic window provided by the cortical breakthrough. Materials and methods: Experiments were conducted on ex vivo lamb shank by mimicking osteolytic bone tumours. The cortical breakthrough was exploited to induce hyperthermia inside the medullar cavity by delivering acoustic energy from a phased array HIFU transducer. MR thermometry data was acquired intra-operatory using the proton resonance frequency shift (PRFS) method. Active temperature control was achieved via a closed-loop predictive controller set at 6 °C above the baseline. Several beam geometries with respect to the cortical breakthrough were investigated. Numerical simulations were used to further explain the observed phenomena. Thermal safety of bone heating was assessed by cross-correlating MR thermometry data with the measurements from a fluoroptic temperature sensor inserted in the cortical bone. Results: Numerical simulations and MR thermometry confirmed the feasibility of spatio-temporal uniform hyperthermia (± 0.5 °C) inside the medullar cavity using a fixed focal point sonication. This result was obtained by the combination of several factors: an optimal positioning of the focal spot in the plane of the cortical breakthrough, the direct absorption of the HIFU beam at the focal spot, the “acoustic oven effect” yielded by the beam interaction with the bone, and a predictive temperature controller. The fluoroptical sensor data revealed no heating risks for the bone and adjacent tissues and were in good agreement with the PRFS thermometry from measurable voxels adjacent to the periosteum. Conclusion: To our knowledge, this is the first study demonstrating the feasibility of MR-guided focused ultrasound hyperthermia inside the medullar cavity of bones affected by osteolytic tumours. Our results are considered a promising step for combining adjuvant mild hyperthermia to external beam radiation therapy for sustained pain relief in patients with symptomatic bone metastases.

Optimization of treatment strategies for prostate cancer patients treated with curative radiation therapy (RT) represents one of the major challenges for the radiation oncologist. Dose escalation or combination of RT with systemic therapies is used to improve tumor control in patients with unfavorable prostate cancer, at the risk of increasing rates and severity of treatment-related toxicities. Elevation of temperature to a supra-physiological level has been shown to both increase tumor oxygenation and reduce DNA repair capabilities. Thus, hyperthermia (HT) combined with RT represents a compelling treatment strategy to improve the therapeutic ratio in prostate cancer patients. The aim of the present systematic review is to report on preclinical and clinical evidence supporting the combination of HT and RT for prostate cancer, discussing future applications and developments of this combined treatment.

High intensity focused ultrasound (HIFU) treatment in the abdominal cavity is challenging due to the respiratory motion. In the self-scanning HIFU ablation method, the focal spot is kept static and the heating pattern is obtained through natural tissue motion. This paper describes a novel approach for modulating the HIFU power during self-scanning in order to compensate for the effect of tissue motion on thermal buildup. The therapy, using hybrid ultrasound (US)/magnetic resonance (MR) imaging, consists of detecting and tracking speckle on US images in order to predict the next tissue position, and modulating the HIFU power according to the tissue speed in order to obtain a rectilinear pattern of uniform temperature elevation. Experiments were conducted on ex vivo tissue subjected to a breathing-like motion generated by an MR-compatible robot and sonicated by a phased array HIFU transducer. US and MR data were free from interferences. For both periodic and non-periodic motion, MR temperature maps showed a substantial improvement in the uniformity of the temperature elevation by using acoustic power modulation. The presented method does not require a learning stage and enables a duty cycle close to 100%, higher average acoustic intensity and avoidance of side lobe effects versus performing HIFU beam steering to compensate tissue motion. To our knowledge, the proposed method provides the first experimental validation of the self-scanning HIFU ablation paradigm via a real-time hybrid MRI/US imaging, opening the path toward self-scanning in vivo therapies.

The effect of micro-droplet concentration on HIFU beam absorption.

High intensity focused ultrasound (HIFU) is clinically accepted for the treatment of solid tumors but remains challenging in highly perfused tissue due to the heat sink effect. Endovascular liquid-...