Bone metastasis treatment using magnetic resonance-guided high intensity focused ultrasound.

Abstract

Bone pain resulting from cancer metastases reduces a patient's quality of life. Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) is a promising alternative palliative thermal treatment technique for bone metastases that has been tested in a few clinical studies. Here, we describe a comprehensive pre-clinical study to investigate the effects, and efficacy of MR-HIFU ablation for the palliative treatment of osteoblastic bone metastases in rats. Prostate cancer cells (MATLyLu) were injected intra-osseously in Copenhagen rats. Upon detection of pain, as determined with a dynamic weight bearing (DWB) system, a MR-HIFU system was used to thermally ablate the bone region with tumor. Treatment effect and efficacy were assessed using magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) with technetium-99m medronate ((99m)Tc-MDP), micro-computed tomography (μCT) and histology. DWB analysis demonstrated that MR-HIFU-treated animals retained 58.6 ± 20.4% of limb usage as compared to 2.6 ± 6.3% in untreated animals (P=0.003). MR-HIFU delayed tumor specific growth rates (SGR) from 29 ± 6 to 13 ± 5%/day (P<0.001). Untreated animals (316.5 ± 78.9 mm(3)) had a greater accumulation of (99m)Tc-MDP than HIFU-treated animals (127.0 ± 42.7 mm(3), P=0.004). The total bone volume increase for untreated and HIFU-treated animals was 15.6 ± 9.6% and 3.0 ± 4.1% (P=0.004), respectively. Histological analysis showed ablation of nerve fibers, tumor, inflammatory and bone cells. Our study provides a detailed characterization of the effects of MR-HIFU treatment on bone metastases, and provides fundamental data, which may motivate and advance its use in the clinical treatment of painful bone metastases with MR-HIFU.