title: Ablation of high-intensity focused ultrasound assisted with SonoVue on Rabbit VX2 liver tumors: sequential findings with histopathology, immunohistochemistry, and enzyme histochemistry.
abstract: BACKGROUND
  We investigated sequential effects of HIFU ablation combined with contrast agent SonoVue by using histopathology examination, immunohistochemistry, and enzyme histochemistry.
  
  
  METHODS
  Forty rabbits with VX2 liver tumors were subjected to HIFU ablation. Before ablation, a bolus injection of 0.2 mL SonoVue was administrated in group II (n = 20), and normal saline solution was injected in group I (n = 20). On day 0, 3, 7, and 14 after ablation, 5 animals in each group were sacrificed. The tissue in ablated zone, transient zone (within 3 mm around ablated area), and surrounding zone (beyond 3 mm around ablated area) were collected. Coagulated volume measurement, hematoxylin-eosin staining, immunohistochemistry of Ki 67, Bcl-2, CD54, and MMP-2 to determine cell proliferation and tissue repair, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and succinic dehydrogenase (SDH) staining to evaluate tissue viability were performed.
  
  
  RESULTS
  The coagulated volume in group II at each time point was larger than that in group I (P < .05). After day 3, hematoxylin-eosin staining demonstrated necrosis in ablated zones and increasing surrounding fibra bands in group I and group II, while increasing expression of Ki 67, Bcl-2, CD54, and MMP-2 in transient zones was detected using immunohistochemistry in both groups (P > .05). NADPH-d and SDH staining showed dramatic decrease of enzyme activities in ablated zones immediately after ablation, while residual viable tissues in ablated zones of group II were less than those of group I (P < .05).
  
  
  CONCLUSIONS
  Contrast agent SonoVue enables improvement of HIFU ablation on rabbit VX2 liver tumors.
authors.affiliation: Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Shaanxi, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Luo
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Guangbin
authors.initials: G
authors.lastname: He
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zheng
authors.forename: Qiuyang
authors.initials: Q
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Zenghui
authors.initials: Z
authors.lastname: Han
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yunqiu
authors.initials: Y
authors.lastname: Qian
mesh_terms: D055011:Ablation Techniques; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D003287:Contrast Media; D007124:Immunoenzyme Techniques; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging*; D010743:Phospholipids; D011817:Rabbits; D013459:Sulfur Hexafluoride; D014464:Ultrasonic Therapy; D014463:Ultrasonography
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride