Mika Petri Ylihautala

Tumour hyperthermia and ablation in rats using a clinical MR-HIFU system equipped with a dedicated small animal set-up

Purpose: We report on the design, performance, and specifications of a dedicated set‐up for the treatment of rats on a clinical magnetic resonance high intensity focused ultrasound (MR‐HIFU) system. Materials and methods: The small animal HIFU‐compatible 4‐channel MR receiver volume coil and animal support were designed as add‐on to a clinical 3T Philips Sonalleve MR‐HIFU system. Prolonged hyperthermia (T ≈ 42°C, 15 min) and thermal ablation (T = 65°C) was performed in vivo on subcutaneous rat tumours using 1.44 MHz acoustic frequency. The direct treatment effect was assessed with T2‐weighted imaging and dynamic contrast enhanced (DCE‐) MRI as well as histology. Results: The developed HIFU‐compatible coil provided an image quality that was comparable to conventional small animal volume coils (i.e. without acoustic window), and a SNR increase by a factor of 10 as compared to the coil set‐up used for clinical MR‐HIFU therapy. The use of an animal support minimised far field heating and allowed precise regulation of the animal body core temperature, which varied <1°C during treatment. Conclusions: The results demonstrated that, by using a designated set‐up, both controlled hyperthermia and thermal ablation treatment of malignant tumours in rodents can be performed on a clinical MR‐HIFU system. This approach provides all the advantages of clinical MR‐HIFU, such as volumetric heating, temperature feedback control and a clinical software interface for use in rodent treatment. The use of a clinical system moreover facilitates a rapid translation of the developed protocols into the clinic.

High intensity focused ultrasound induced in vivo large volume hyperthermia under 3D MRI temperature control.

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.

Drift correction for accurate PRF-shift MR thermometry during mild hyperthermia treatments with MR-HIFU

Abstract There is growing interest in performing hyperthermia treatments with clinical magnetic resonance imaging-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 proton resonant frequency (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 a 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 min was evaluated in rabbit experiments. Results: Automatic centre-frequency adjustments prior to image-acquisition corrected the image-shifts in 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 centre-frequency adjustment and the combined drift correction algorithm was 0.57° ± 0.58 °C in the heated region and 0.54° ± 0.42 °C in the 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, centre-frequency adjustment eliminated image shifts, and a combined drift correction algorithm achieved temperature measurements with an acceptable accuracy for monitoring and controlling hyperthermia exposures.

Evaluation of intensity based beam-shaping method with Rib-phantom HIFU sonications

The relation between rib bone heating during HIFU therapy and incident intensity on the bone surface was examined using an experimental setup and simulations with ray-tracer. The relation was found to be linear yet the data had large variance. The result was successfully applied to an intensity-based beam-shaping algorithm, which was fast enough for online therapy planning, and used to protect the ribs from overheating during intercostal sonications to a HIFU phantom containing two porcine rib bones.

Near-field heating of volumetric MR-HIFU hyperthermia

Excessive heating of the skin and other near-field tissues is a safety issue for all highintensity ultrasound (HIFU) sonications, but is of particular concern for large energy sonications. Even though hyperthermia experiments tend to use low sonication powers the extended period of time that may easily be several tens of minutes cause a significant amount of energy to be deposited during the sonication. An improved understanding of the effect of different sonication and tissue parameters on the near-field heating should aid in improving the safety of high-energy HIFU sonications. We recently showed the near-field heating to be linearly dependent on the near-field energy density for high-power in vivo volumetric ablations of duration 5-139 s. However, as sonication duration is further increased the near-field heating rate is expected to slow down due to diffusion and perfusion and converge towards a steady state temperature distribution. Here, the near-field heating of hyperthermia duration sonications is ...