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Heating and Coagulation Volume Obtained with High-Intensity Focused Ultrasound Therapy: Comparison of Perflutren Protein-Type A Microspheres and MRX-133 in Rabbits¹

¹ From the Departments of Surgical Oncology (K.T., T.W., H.N.), Mechanical Engineering (Y.K., S.W., Y.M.), and Gastroenterology (T.M.), University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. Received August 19, 2004; revision requested October 27; revision received November 19; accepted December 14. Supported in part by a grant-in-aid from the Ministry of Education, Science, Sports, Culture, and Technology of Japan and in part by grants from the Ministry of Health, Labor, and Welfare of Japan. Address correspondence to K.T. (e-mail: ktakegami-tky{at}umin.ac.jp).

PURPOSE: To compare the efficiency of different microbubble contrast agents in the heating and coagulation of rabbit liver tissue by using high-intensity focused ultrasound therapy.

MATERIALS AND METHODS: The use of and protocols for Japan white rabbits were approved by the University of Tokyo Committee on Animal Resources. In vitro experiments were conducted in a 1-mL cylindric space of polyacrylamide gel, which contained different microbubble contrast agents (MRX-133 or perflutren protein-type A microspheres). In vivo experiments were performed in six Japan white rabbits (two for the perflutren protein-type A microsphere group, two for the MRX-133 group, and two for the control group). In each rabbit, the liver was directly subjected to high-intensity focused ultrasound after intravenous injection of different microbubble contrast agents. Natural saline was used as a control. High-intensity focused ultrasound was applied for 30 seconds by using a 2.18-MHz transducer, and the temperature increase and volume of coagulation necrosis were evaluated. Statistical analysis was performed by using an analysis of variance test, which was followed by a Student-Newman-Keuls test; a P value of <.05 was considered to indicate a statistically significant difference.

RESULTS: In the MRX-133 group, the mean temperature increase was significantly greater and faster than that in the control group (P < .01) or in the perflutren protein-type A microsphere group (P < .05). In the perflutren protein-type A microsphere group, the mean temperature increase was greater and faster than that of the control group (P < .01) for both in vitro and in vivo experiments. The mean volume of the coagulation necrosis lesion was 117.9 mm³ ± 48.4 (±standard deviation) for the MRX-133 group, 45.4 mm³ ± 24.9 for the perflutren protein-type A microsphere group, and 17.7 mm³ ± 9.0 for the control group. In the MRX-133 group, the mean volume of coagulation necrosis was significantly greater than that of the control or the perflutren protein-type A microsphere group (P < .01), and in the perflutren protein-type A microsphere group, the volume of coagulation necrosis was greater than that of the control group (P < .05).

CONCLUSION: MRX-133 had greater efficiency than perflutren protein-type A microspheres in high-intensity focused ultrasound–induced heating and coagulation of rabbit liver tissue.

© RSNA, 2005

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