title: Comparison of the synergistic effect of lipid nanobubbles and SonoVue microbubbles for high intensity focused ultrasound thermal ablation of tumors.
abstract: Microbubbles (MBs) are considered as an important enhancer for high intensity focused ultrasound (HIFU) treatment of benign or malignant tumors. Recently, different sizes of gas-filled bubbles have been investigated to improve the therapeutic efficiency of HIFU thermal ablation and reduce side effects associated with ultrasound power and irradiation time. However, nanobubbles (NBs) as an ultrasound contrast agent for synergistic therapy of HIFU thermal ablation remain controversial due to their small nano-size in diameter. In this study, phospholipid-shell and gas-core NBs with a narrow size range of 500-600 nm were developed. The synergistic effect of NBs for HIFU thermal ablation was carefully studied both in excised bovine livers and in breast tumor models of rabbits, and made a critical comparison with that of commercial SonoVue microbubbles (SonoVue MBs). In addition, the pathological changes of the targeted area in tumor tissue after HIFU ablation were further investigated. Phosphate buffer saline (PBS) was used as the control. Under the same HIFU parameters, the quantitative echo intensity of B-mode ultrasound image and the volume of coagulative necrosis in lipid NBs groups were significantly higher and larger than that in PBS groups, but could not be demonstrated a difference to that in SonoVue MBs groups both ex vivo and in vivo. These results showed that the synergistic effect of lipid NBs for HIFU thermal ablation were similar with that of SonoVue MBs, and further indicate that lipid NBs could potentially become an enhancer for HIFU thermal ablation of tumors.
authors.affiliation: Chongqing Key Laboratory of Ultrasound Molecular Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University , Chongqing , China.
authors.forename: Yuanzhi
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Ultrasound, Children's Hospital of Chongqing Medical University, Chongqing Medical University , Chongqing , China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Chongqing Key Laboratory of Ultrasound Molecular Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University , Chongqing , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Emergency, Chinese PLA General Hospital , Beijing , China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Ultrasound Molecular Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University , Chongqing , China.
authors.forename: Jinshun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Chongqing Key Laboratory of Ultrasound Molecular Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University , Chongqing , China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Ultrasound Engineering in Medical of Chongqing Medical University, Chongqing Medical University , Chongqing , China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Chongqing Key Laboratory of Ultrasound Molecular Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University , Chongqing , China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Chongqing Key Laboratory of Ultrasound Molecular Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China; Department of Ultrasound, Children's Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
keywords: High intensity focused ultrasound; Microbubbles; Nanobubbles; Tumor therapy