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© 2007 by the American Institute of Ultrasound in Medicine
J Ultrasound Med 26:469-476 • 0278-4297

Enhancing Effects of SonoVue, a Microbubble Sonographic Contrast Agent, on High-Intensity Focused Ultrasound Ablation in Rabbit Livers In Vivo

Wen Luo, MSc, Xiaodong Zhou, PhD, Xiaolong Ren, MSc, Minjuan Zheng, PhD, Jun Zhang, PhD and Guangbin He, MSc

Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi’an, China.

Address correspondence to Xiaodong Zhou, PhD, Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, 17 Changle Xilu, 710032 Xi’an, China. E-mail: zhouxdong{at}gmail.com

Objective. The purpose of this study was to explore the enhancing biological effects of SonoVue (Bracco SpA, Milan, Italy), a sulfur hexafluoride sonographic contrast agent, on high-intensity focused ultrasound (HIFU) ablation in vivo. Methods. Forty-five rabbits were randomly divided into 3 groups and underwent laparotomy. Animals in group 1 were given injections of 0.2 mL of SonoVue intravenously; animals in group 2 were given physiologic saline; and those in group 3 were not given injections as control. The exposure time was set at 2 seconds with the acoustic power at 600 W. After HIFU ablations, volumes of coagulated regions were measured. Liver tissues were examined under light microscopy with hematoxylin-eosin staining and under transmission electron microscopy. Results. Coagulated volumes in group 1 (mean ± SD, 2.41 ± 0.44 cm3) were larger than those in group 2 (0.80 ± 0.13 cm3) and group 3 (0.83 ± 0.16 cm3) (P < .05). Separated from the surrounding area with a clear demarcation line, the targeted area in each group showed a few necrotic cells on light microscopy with the hematoxylin-eosin stain. More bubbles were observed under light microscopy in exposed areas in group 1 than in the other 2 groups (P < .05). Electron microscopy showed more severe cell ultrastructure disorder, including more interrupted cell nuclear membranes, in targeted areas in group 1 than in the other 2 groups. Conversely, in all the groups, untreated areas were not affected. Conclusions. SonoVue can substantially enhance the ablation effects of HIFU, suggesting that microbubble contrast agents may be useful for improving HIFU efficiency.

Key Words: contrast agent • high-intensity focused ultrasound • microbubble • rabbit

Abbreviations: H&E, hematoxylin-eosin • HIFU, high-intensity focused ultrasound • ISPTA, spatial-peak temporal-average intensity

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Copyright © 2007 by the American Institute of Ultrasound in Medicine.