Heating and coagulation volume obtained with high-intensity focused ultrasound therapy: comparison of perflutren protein-type A microspheres and MRX-133 in rabbits.

Abstract

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