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


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 ((99m)Tc-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 ± 78.9 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.


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.
Department of Biomedical Engineering, Eindhoven University of Technology, High Tech Campus 11-p1.243, 5656 AE Eindhoven, The Netherlands. Electronic address: s.y.yeo@tue.nl.
Sin Yuin
SY
Yeo
Philips Research Europe, High Tech Campus 11-p1.261A, 5656 AE Eindhoven, The Netherlands. Electronic address: aaldert.elevelt@philips.com.
Aaldert
A
Elevelt
Philips Research Europe, High Tech Campus 11-p1.261A, 5656 AE Eindhoven, The Netherlands. Electronic address: katia.donato@philips.com.
Katia
K
Donato
Department of Biomedical Engineering, Eindhoven University of Technology, High Tech Campus 11-p1.243, 5656 AE Eindhoven, The Netherlands. Electronic address: B.v.Rietbergen@tue.nl.
Bert
B
van Rietbergen
Department of Pathology, University Medical Center Utrecht, Room H04.312, Utrecht, The Netherlands. Electronic address: N.terHoeve@umcutrecht.nl.
Natalie D
ND
Ter Hoeve
Department of Pathology, University Medical Center Utrecht, Room H04.312, Utrecht, The Netherlands. Electronic address: P.J.vanDiest@umcutrecht.nl.
Paul J
PJ
van Diest
Department of Biomedical Engineering, Eindhoven University of Technology, High Tech Campus 11-p1.243, 5656 AE Eindhoven, The Netherlands; Philips Research Europe, High Tech Campus 11-p1.261A, 5656 AE Eindhoven, The Netherlands. Electronic address: h.gruell@tue.nl.
Holger
H
Grüll
D000818:Animals; D001859:Bone Neoplasms / Q000175:diagnosis / Q000556:secondary* / Q000628:therapy*; D016723:Bone Remodeling; D045744:Cell Line, Tumor; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000556:secondary / Q000628:therapy; D059408:Pain Management; D010166:Palliative Care; D019275:Radiopharmaceuticals; D051381:Rats; D013669:Technetium Tc 99m Medronate; D015899:Tomography, Emission-Computed, Single-Photon; D055114:X-Ray Microtomography
D019275:Radiopharmaceuticals; D013669:Technetium Tc 99m Medronate
Bone metastases; Focused ultrasound; HIFU; Palliative treatment