TY - JOUR
T1 - Bone metastasis treatment using magnetic resonance-guided high intensity focused ultrasound
AU - Yeo, Sin Yuin
AU - Elevelt, Aaldert
AU - Donato, Katia
AU - van Rietbergen, Bert
AU - ter Hoeve, Natalie D.
AU - van Diest, Paul J.
AU - Grüll, Holger
N1 - Funding Information:
We would like to thank Knut Liepe (Klinikum Frankfurt (Oder) GmbH, Germany) for his advice and assistance on setting up the bone metastasis model, Edwin Heijman (Philips Research, The Netherlands) for all support on the MR-HIFU system, Suzanne Kivits, Monique Berben, Iris Verel (Philips Research, The Netherlands), Caren van Kammen, Marije Janssen and Marleen Hendriks (Maastricht University, The Netherlands) for their excellent support with the in vivo experiments and Sander Langereis (Philips Research, The Netherlands) for the fruitful discussion. This research was supported by the Center for Translational Molecular Medicine (HIFU-CHEM, Grant 03O-301 ).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Objectives: 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. Materials and methods: 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 (99mTc-MDP), micro-computed tomography (μCT) and histology. Results: 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±78.9mm3) had a greater accumulation of 99mTc-MDP than HIFU-treated animals (127.0±42.7mm3, 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. Conclusions: 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.
AB - Objectives: 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. Materials and methods: 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 (99mTc-MDP), micro-computed tomography (μCT) and histology. Results: 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±78.9mm3) had a greater accumulation of 99mTc-MDP than HIFU-treated animals (127.0±42.7mm3, 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. Conclusions: 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.
KW - Bone metastases
KW - Focused ultrasound
KW - HIFU
KW - Palliative treatment
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U2 - 10.1016/j.bone.2015.08.025
DO - 10.1016/j.bone.2015.08.025
M3 - Article
C2 - 26325304
AN - SCOPUS:84941247748
VL - 81
SP - 513
EP - 523
JO - Bone
JF - Bone
SN - 8756-3282
ER -