title: Quantitative evaluation of viable tissue perfusion changes with contrast-enhanced greyscale ultrasound in a mouse hepatoma model following treatment with different doses of thalidomide.
abstract: OBJECTIVE
  This study aimed to quantify intratumoural viable tissue perfusion with contrast-enhanced greyscale ultrasound to evaluate tumour response to anti-angiogenic treatment.
  
  
  METHODS
  H22 hepatoma-bearing mice were treated with low-dose thalidomide (Group B), high-dose thalidomide (Group C) or 0.5% carboxylmethylcellulose (Group A). Contrast-enhanced greyscale ultrasound was performed after 7 days of treatments to evaluate the percentage of non-enhanced area for each tumour; regions of interest within the enhanced area were analysed offline to determine the area under the curve (AUC), maximum intensity (IMAX), perfusion index (PI), mean transit time (MTT), time to peak (TTP) and quality of fit (QOF). Immunohistochemical analysis was performed for evaluation of microvascular density (MVD).
  
  
  RESULTS
  The percentage of non-enhanced area was significantly larger in Group C than in Groups A and B (p<0.05); however, there was no significant difference between Groups A and B. Treatment with thalidomide resulted in a significant decrease in AUC, PI and IMAX compared with Group A (p<0.05). Immunohistochemistry showed significant decreases in MVD in Groups B and C compared with Group A (p<0.05); however, there was no significant difference in MVD between Groups B and C. MVD was positively correlated with IMAX (r = 0.419, p = 0.023) and PI (r = 0.455, p = 0.013).
  
  
  CONCLUSIONS
  Quantitatively analysing intratumoural viable tissue perfusion enables early evaluation of tumour response to anti-angiogenic therapy before apparent changes in tumour necrosis.
authors.affiliation: Department of Ultrasound, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou, People's Republic of China, 510060.
authors.forename: J H
authors.initials: JH
authors.lastname: Zhou
authors.forename: W
authors.initials: W
authors.lastname: Zheng
authors.forename: L H
authors.initials: LH
authors.lastname: Cao
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: R Z
authors.initials: RZ
authors.lastname: Luo
authors.forename: F
authors.initials: F
authors.lastname: Han
authors.forename: P H
authors.initials: PH
authors.lastname: Wu
authors.forename: A H
authors.initials: AH
authors.lastname: Li
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D003287:Contrast Media; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D013792:Thalidomide / Q000008:administration & dosage*; D014463:Ultrasonography
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D013792:Thalidomide