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使用半定量动态对比增强磁共振成像参数评估肿瘤缺氧:在兔颌面VX2模型中的临床前可行性研究

Using semi-quantitative dynamic contrast-enhanced magnetic resonance imaging parameters to evaluate tumor hypoxia: a preclinical feasibility study in a maxillofacial VX2 rabbit model.

作者信息

Zheng Linfeng, Li Yujie, Geng Feng, Zheng Sujuan, Yan Ruiling, Han Yuedong, Wang Qiben, Zhang Zhuoli, Zhang Guixiang

机构信息

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.

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.

出版信息

Am J Transl Res. 2015 Mar 15;7(3):535-47. eCollection 2015.

PMID:26045893
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4448193/
Abstract

PURPOSE

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.

摘要

目的

在兔颌面VX2肿瘤模型中,探讨半定量动态对比增强磁共振成像(DCE-MRI)参数评估肿瘤缺氧的可行性。

方法

8只新西兰兔接种VX2细胞溶液,建立兔颌面VX2肿瘤模型。采用1.5T磁共振扫描仪行DCE-MRI检查,计算并分析半定量DCE-MRI参数,即最大强化率(MER)和强化斜率(SLE)。兔肿瘤标本行苏木精-伊红(HE)染色、匹莫硝唑(PIMO)及血管内皮生长因子(VEGF)免疫组化(IHC)染色,计算PIMO面积分数和VEGF IHC评分。采用Spearman等级相关分析进行统计学分析。

结果

8个VX2肿瘤的MER值为1.1321.773(1.406±0.258),与相应的PIMO面积分数呈负相关(p=0.0000002),与匹配的VEGF IHC评分无显著相关性(p=0.578)。8个VX2肿瘤的SLE值为0.01980.0532 s-1(0.030±0.011 s-1)。相关分析显示,SLE与相应的VEGF IHC评分呈正相关(p=0.0149)。然而,SLE与匹配的PIMO面积分数无相关性(p=0.662)。除肿瘤血管相邻区域外,VEGF阳性染色分布主要与PIMO加合物区域重叠。

结论

DCE-MRI的半定量参数MER和SLE能够可靠地测量肿瘤缺氧情况,可用于肿瘤治疗期间缺氧情况的无创评估。