Using microbubble contrast agent of different dosage to enhancing liver ablation induced by high-intensity focused ultrasound

Abstract

Objective: To investigate the enhancing biological effect of different dosages of microbubble contrast agent on High-Intensity Focused Ultrasound (HIFU) ablation in goat livers in vivo. Methods: Twenty goats were divided into 4 groups randomly. Animals in group 1, 2 and 3 were bolus-injected with 0.01ml/kg/dot, 0.03ml/kg/dot and 0.05ml/kg/dot of SonoVue (Bracco SpA, Milan, Italy) intravenously respectively before HIFU exposure; and those in group 4 were not given injections as control. The livers were ablated using HIFU performed in the manner of a single dot using a clinical device. The frequency of HIFU was 0.8MHz; the intensity of HIFU was 19000W/cm2.The distance from skin to the target liver tissue was 30mm. The exposure time was set at 15S for all animals. All animals were euthanized 7 days after HIFU, and volumes of coagulated necrosis were measured. Pathological examinations were performed to determine whether there were residual intact tissues within the exposure regions. Results: Coagulated volumes in group 1, 2, 3 were larger than those in group 4, with significant difference (p<0.05). The coagulated volumes increased gradually from group 1 to group 3, with significant difference (p<0.05). Pathological examinations confirmed that there were no residual unaffected tissues within the exposed volume. Two remarkable changes occurred in one goat in group 3 seven days after HIFU: The surrounding adjacent tissues outside the reactive zone were necrotized, and the overlying liver tissues were destroyed. Conclusions: These findings showed that the enhancing effect of microbubble contrast agent in HIFU ablation was related with the dosage of the microbubble contrast agent SonoVue. The higher the dosage, the larger the volume destroyed in the target tissue. However, when exceeding a certain dosage level, SonoVue would give a negative impact on HIFU ablation, which awaits further study in future. Conclusions: These findings showed that the enhancing effect of microbubble contrast agent in HIFU ablation was related with the dosage of the microbubble contrast agent SonoVue. The higher the dosage, the larger the volume destroyed in the target tissue. However, when exceeding a certain dosage level, SonoVue would give a negative impact on HIFU ablation, which awaits further study in future.