title: Using semi-quantitative dynamic contrast-enhanced magnetic resonance imaging parameters to evaluate tumor hypoxia: a preclinical feasibility study in a maxillofacial VX2 rabbit model.
abstract: OBJECTIVE
  To test the feasibility of semi-quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters for evaluating tumor hypoxia in a maxillofacial VX2 rabbit model.
  
  
  METHODS
  Eight New Zealand rabbits were inoculated with VX2 cell solution to establish a maxillofacial VX2 rabbit model. DCE-MRI were carried out using a 1.5 Tesla scanner. Semi-quantitative DCE-MRI parameters, maximal enhancement ratio (MER) and slope of enhancement (SLE), were calculated and analyzed. The tumor samples from rabbits underwent hematoxylin-eosin (HE), pimonidazole (PIMO) and vascular endothelial growth factor (VEGF) immunohistochemistry (IHC) staining, and the PIMO area fraction and VEGF IHC score were calculated. Spearman's rank correlation analysis was used for statistical analysis.
  
  
  RESULTS
  The MER values of eight VX2 tumors ranged from 1.132 to 1.773 (1.406 ± 0.258) and these values were negatively correlated with the corresponding PIMO area fraction (p = 0.0000002), but there was no significant correlation with the matched VEGF IHC score (p = 0.578). The SLE values of the eight VX2 tumors ranged from 0.0198 to 0.0532 s(-1) (0.030 ± 0.011 s(-1)). Correlation analysis showed that there was a positive correlation between SLE and the corresponding VEGF IHC score (p = 0.0149). However, no correlation was found between SLE and the matched PIMO area fraction (p = 0.662). The VEGF positive staining distribution predominantly overlapped with the PIMO adducts area, except for the area adjacent to the tumor blood vessel.
  
  
  CONCLUSIONS
  The semi-quantitative parameters of DCE-MRI, MER and SLE allowed for reliable measurements of the tumor hypoxia, and could be used to noninvasively evaluate hypoxia during tumor treatment.
authors.affiliation: Department of Radiology, Shanghai First People's Hospital, Shanghai Jiao Tong University Shanghai 200080, China ; Department of Radiology, Feinberg School of Medicine, Northwestern University Chicago, IL 60611, USA.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Radiology, Shanghai First People's Hospital, Shanghai Jiao Tong University Shanghai 200080, China ; Department of Radiology, Zhangjiagang First People's Hospital Zhangjiagang 215600, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of The Thyroid Gland and Breast Surgery, Department of Surgery, Zhangjiagang First People's Hospital Zhangjiagang 215600, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Geng
authors.affiliation: Dengfeng People's Hospital Zhengzhou 452470, China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Ultrasound, General Hospital of Lanzhou Military Region Lanzhou 730050, China.
authors.forename: Ruiling
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Radiology, General Hospital of Lanzhou Military Region Lanzhou 730050, China.
authors.forename: Yuedong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Histology and Embryology, Xiangya School of Medicine, Central South University Changsha 410013, China.
authors.forename: Qiben
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Radiology, Feinberg School of Medicine, Northwestern University Chicago, IL 60611, USA.
authors.forename: Zhuoli
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Shanghai First People's Hospital, Shanghai Jiao Tong University Shanghai 200080, China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
keywords: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); VX2 tumor; hypoxia; imaging biomarker; rabbits; semi-quantitative analysis