Enhancing ablation effects of a microbubble contrast agent on high-intensity focused ultrasound: an experimental and clinical study

Objective To investigate the relationship between SonoVue ablation enhancement effects on high-intensity focused ultrasound (HIFU) and the concentration of SonoVue and timing of HIFU. Design Two randomised controlled trials. Setting An animal centre in a university and a gynaecological department in a university hospital in China. Population or sample 63 rabbits and 143 patients with a solitary uterine fibroid. Methods Among the 63 rabbits, three were assigned to the control group. The other 60 were evenly assigned to three study groups pretreated with 0.03, 0.05 or 0.07 ml/kg of SonoVue before HIFU treatment. Two points in each liver were selected to be treated with HIFU and sonication started at 10, 30, 60, 90, 120, 150, 180, 210, 250 or 300 seconds after the administration of SonoVue, respectively. The 143 patients with solitary uterine fibroids were assigned to four groups: 30 patients were treated using only HIFU; the other patients were pretreated with same dosage of SonoVue and 32, 38 and 43 were treated with HIFU at 1-, 3-, and 5-minutes after administration of SonoVue, respectively. Main outcome measures The relation between SonoVue ablation enhancement effects on HIFU and the concentration of SonoVue and timing of HIFU. Results In the experimental study, the highest temperature and the largest necrotic volume in the liver were observed when HIFU sonication started at 60 seconds after administration of SonoVue. In the clinical study, the rate of significant grey-scale changes in the 1-minute SonoVue group was significantly greater than in the other three groups. The sonication time to reach massive grey-scale changes measured in the 1-minute SonoVue group was significantly shorter than in in the other three groups. The sonication time for ablating 1 cm 3 of fibroid volume in the 1-minute SonoVue group was significantly shorter than in the other three groups. The acoustic energy used in treating 1 mm 3 of uterine fibroid in the 1-minute SonoVue group was significantly less than that used in the other three groups. No major complications occurred in this study. Conclusions SonoVue could safely be used to enhance the ablation effects of HIFU treatment, and the optimal time to begin HIFU sonication seems to be 1 minute after the administration of SonoVue.