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

Abstract

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 greyscale 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.Keywords Enhancing effects, high-intensity focused ultrasound, rabbit liver, SonoVue, uterine fibroids.Tweetable abstract SonoVue, a microbubble contrast agent, enhanced the ablation effects of HIFU treatment; the optimal time to begin HIFU sonication appears to be 1 minute after the administration of SonoVue.

Clinical significance of performing Sonazoid-based contrast-enhanced ultrasonography before ablation of uterine fibroids by high-intensity focused ultrasound

“…As sacrococcygeal pain could be related to tissue injury due to the penetration of HIFU beyond the target region to the sacrococcygeal region, it can be concluded that the use of a lower total energy in the CEUS+HIFU group may reduce HIFU-induced tissue injury in the sacrococcygeal region. In agreement with results of the present study, Jiang et al [ 16 ] and Cheng et al [ 18 ] reported a significantly smaller EEF and a lower incidence of sacrococcygeal pain in SonoVue-based CEUS group compared with control group.…”

“…These effects of residual Sonazoid may enable HIFU to achieve the same level of ablation with a lower amount of energy. [ 18 , 19 , 47 ]…”

“…A balloon filled with degassed water was placed between the transducer and patient's abdominal wall when bowel appeared in the acoustic pathway. HIFU therapy was carried out under intravenous conscious sedation [ 15 , 16 , 18 ] with fentanyl (50–400 μg) and midazolam hydrochloride (1–4 mg). Vital signs, including heart and respiration rates, blood pressure, and oxygen saturation level, were monitored continuously during HIFU ablation, and the patient was requested to report any discomfort during the procedure.…”

Functional micro/nanobubbles for ultrasound medicine and visualizable guidance

“…The MBs with HIFU can enhance ablation effects. Bai [85] pretreated with SonoVue and introduced them into rabbits and patients with a solitary uterine fibroid. 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.…”

Introducing clinical protocol for ultrasound-guided high-intensity focused ultrasound ablation of uterine fibroids in patients in Europe, provided from experienced Chinese center-prospective comparative

“…The microbubbles, which the contrast agents are made of, can make acoustic changes of the tissues and make HIFU treatment more efficient. There are many studies that show the use of contrast-enhanced HIFU treatment has effects and proved that SonoVue is safety and can be used in treatment of uterine fibroids to enhance the ablation effects of HIFU [6]. Most of them were performed in Asia.…”