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Kunyan He,1 Haitao Ran,2,3 Zhongzhen Su,1 Zhigang Wang,2,3 Maoping Li,4 Lan Hao3 1Ultrasound Department, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, People’s Republic of China; 2Ultrasound Department, The second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China; 3The Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing 400010, People’s Republic of China; 4Ultrasound Department, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China Purpose: The objective of this study was to develop a multifunctional contrast agent for bioimaging and synergistic high-intensity focused ultrasound (HIFU) therapy to achieve theranostic.Materials and methods: A novel type of perfluorohexane-encapsulated fullerene (PFH-C60) nanosphere was successfully developed via a vacuum ultrasonic emulsification and centrifugation method and subsequently used in ultrasound/computed tomography (CT) dual-modality and HIFU ablation of dissected bovine livers. In addition, transmission electron microscopic examination was employed to detect structural changes in the target tissue for HIFU ablation.Results: The use of composite nanospheres effectively enhanced ultrasound and CT imaging. Moreover, the HIFU ablation of dissected bovine livers was also significantly enhanced.Conclusion: Composite nanospheres demonstrate potential theranostic application as a multifunctional contrast agent for dual-modality biological imaging and highly efficient synergistic imaging-guided HIFU ablation. Keywords: microbubble, noninvasive therapy, double modal imaging, sonodynamic effects, synergistic ablation efficiency