Vascular disruption effects of HepG2 tumor by microbubble desruption-re-desruption

Objective To investigate the change of HepG2 liver tumor perfusion after microbubble enhanced ultrasound cavitation treatment and observe the related pathological injury.Methods Twenty eight Balb/c(nu/nu) nude mice transplanted subcutaneous HepG2 tumor were divided into three groups randomly,including the microbubble enhanced ultrasound cavitation group,the ultrasound group and the sham group.Microbubble enhanced ultrasound cavitation treatment was performed by 0.1 ml microbubbles intravenous injection combined with pulse ultrasound emission in experimental group,while in control groups only ultrasound exposure or microbubble injection were applied.The perfusion of tumors was imaged using contrast-enhanced ultrasonography before and after treatments.Time-intensity curve and peak intensity were analyzed.The tumors were then harvested for histological examination.Results The perfusion of HepG2 tumors almost vanished immediately after treatment in experimental group,with the peak intensity reduced from (26.9 ± 10.9)％ to(8.2 ± 5.8)％ (P ＜0.05).There was no significant changes before and after treatments (P ＞ 0.05) in the two control groups.Histological findings were disruption of the endothelia,significant hemorrhage and increased intercellular fluid.Conclusions Microbubble-enhanced ultrasound cavitation can significantly reduce tumor blood perfusion and disrupt tumor vascularture.This new ultrasound therapy can potentially become a new physical anti-angiogenetic therapy for liver tumor. Key words: Ultrasonography ;  Microbubbles ;  Liver neoplasms ;  Neovascularization, pathological