Abstract

MRI guided Focused Ultrasound (MRgFUS) has shown to be effective therapeutic modality for non-invasive clinical interventions in ablating of uterine fibroids, in bone metastasis palliative treatments, and in breast, liver, and prostate cancer ablation. MRgFUS combines high intensity focused ultrasound (HIFU) with MRI images for treatment planning and real time thermometry monitoring, thus enabling non-invasive ablation of tumor tissue. Although in the literature there are several studies on the Ultrasound (US) effects on cell in culture, there is no systematic evidence of the biological effect of Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) treatment on osteosarcoma cells, especially in lower dose regions, where tissues receive sub-lethal acoustic power. The effect of MRgFUS treatment at different levels of acoustic intensity (15.5-49 W/cm2) was investigated on Mg-63 and Saos-2 cell lines to evaluate the impact of the dissipation of acoustic energy delivered outside the focal area, in terms of cell viability and osteogenic differentiation at 24 h, 7 days, and 14 days after treatment. Results suggested that the attenuation of FUS acoustic intensities from the focal area (higher intensities) to the “far field” (lower intensities) zones might determine different osteosarcoma cell responses, which range from decrease of cell proliferation rates (from 49 W/cm2 to 38.9 W/cm2) to the selection of a subpopulation of heterogeneous and immature living cells (from 31.1 W/cm2 to 15.5 W/cm2), which can clearly preserve bone tumor cells.

Highlights

  • Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS), an image-guided non-invasive therapeutic treatment, is increasingly becoming popular for cancer ablation [1]

  • The results suggest that a subpopulation of osteosarcoma cell lines, probably more prone to proliferation, survive in the presence of FUS mechanical and attenuated thermal effects and grow up to 14 days, expressing osteoblastic markers even 7 or 14 days after the treatment, even in experimental conditions that are usually applied for thermoablation (38.9-49 W/cm2)

  • Our preliminary in vitro study suggested that osteosarcoma cell lines, treated with different FUS acoustic intensity levels, had a different ability to maintain or lose their differentiation state and relative proliferation capability

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Summary

Introduction

Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS), an image-guided non-invasive therapeutic treatment, is increasingly becoming popular for cancer ablation [1]. MRgFUS has been recently adopted for the treatment of bone tumors, including benign tumors, primary malignancies, and metastatic bone tumors [2, 3]. Rodrigues et al have analyzed results of fifteen clinical studies evaluating the effect of MRgFUS for non-invasive treatment of bone tumors at different levels of severity, showing a FUS efficacy of 92-100 %, 85-87 %, and 6487 % for primary benign, primary malignant, and metastatic tumors, respectively [6]. Other studies revealed that patients treated for primary malignant tumors have a higher risk of complications, highlighting that the question of FUS treatment safety is still under debate [1, 4, 7, 8]. The high acoustic impedance of cortical bone makes full

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