title: Three-dimensional contrast enhanced ultrasound score and dynamic contrast-enhanced magnetic resonance imaging score in evaluating breast tumor angiogenesis: correlation with biological factors.
abstract: OBJECTIVE
  To explore the clinical value of three-dimensional contrast enhanced ultrasound (3D-CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) score systems in evaluating breast tumor angiogenesis by comparing their diagnostic efficacy and correlation with biological factors.
  
  
  METHODS
  3D-CEUS was performed in 183 patients with breast tumors by Esaote Mylab90 with SonoVue (Bracco, Italy), DCE-MRI was performed on a dedicated breast magnetic resonance imaging (DBMRI) system (Aurora Dedicated Breast MRI Systems, USA) with a dedicated breast coil. 3D-CEUS and DCE-MRI score systems were created based on tumor perfusion and vascular characteristics. Microvessel density (MVD), vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP-2, MMP-9) expression were measured by immunohistochemistry.
  
  
  RESULTS
  Pathological results showed 35 benign and 148 malignant breast tumors. MVD (P=0.000, r=0.76), VEGF (P=0.000, r=0.55), MMP-2 (P=0.000, r=0.39) and MMP-9 (P=0.000, r=0.41) expression were all significantly different between benignity and malignancy. Regarding 3D-CEUS 4 points as cutoff value, the sensitivity, specificity and accuracy were 85.1%, 94.3% and 86.9%, respectively, and correlated well with MVD (P=0.000, r=0.50), VEGF (P=0.000, r=0.50), MMP-2 (P=0.000, r=0.50) and MMP-9 (P=0.000, r=0.66). Taking DCE-MRI 5 points as cutoff value, the sensitivity, specificity and accuracy were 86.5%, 94.3% and 88.0%, respectively and also correlated well with MVD (P=0.000, r=0.52), VEGF (P=0.000, r=0.44), MMP-2 (P=0.000, r=0.42) and MMP-9 (P=0.000, r=0.35).
  
  
  CONCLUSIONS
  3D-CEUS score system displays inspiring diagnostic performance and good agreement with DCE-MRI scoring. Moreover, both score systems correlate well with MVD, VEGF, MMP-2 and MMP-9 expression, and thus have great potentials in tumor angiogenesis evaluation.
authors.affiliation: Department of Diagnostic Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, No. 197 Rui Jin 2nd Road, Shanghai 200025, China. Electronic address: jiawanru@126.com.
authors.forename: Wan-Ru
authors.initials: WR
authors.lastname: Jia
authors.affiliation: Department of Radiology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, No. 197 Rui Jin 2nd Road, Shanghai 200025, China. Electronic address: chai_weimin@yahoo.com.cn.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chai
authors.affiliation: Department of Diagnostic Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, No. 197 Rui Jin 2nd Road, Shanghai 200025, China. Electronic address: jessietang1003@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Diagnostic Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, No. 197 Rui Jin 2nd Road, Shanghai 200025, China. Electronic address: xiatian.0602@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, No. 197 Rui Jin 2nd Road, Shanghai 200025, China. Electronic address: xcf0222@163.com.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Fei
authors.affiliation: Department of Comprehensive Breast Health Center, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, No. 197 Rui Jin 2nd Road, Shanghai 200025, China. Electronic address: hanbaosan@126.com.
authors.forename: Bao-San
authors.initials: BS
authors.lastname: Han
authors.affiliation: Department of Diagnostic Ultrasound, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, No. 197 Rui Jin 2nd Road, Shanghai 200025, China. Electronic address: lucyjia1370@126.com.
authors.forename: Man
authors.initials: M
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis*; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood / Q000175:diagnosis*; D015588:Observer Variation; D010743:Phospholipids; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D013459:Sulfur Hexafluoride; D016217:Ultrasonography, Mammary / Q000379:methods*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D019786:Gadolinium DTPA; D013459:Sulfur Hexafluoride
keywords: Angiogenesis; Biological factors; Breast tumor; Contrast-enhanced ultrasound; Dynamic contrast-enhanced magnetic resonance imaging; Three-dimensional ultrasound