使用体素内不相干运动扩散加权磁共振成像和组织病理学对胃癌小鼠模型中的化疗反应进行评估。

Chemotherapy response evaluation in a mouse model of gastric cancer using intravoxel incoherent motion diffusion-weighted MRI and histopathology.

作者信息

Cheng Jin, Wang Yi, Zhang Chun-Fang, Wang He, Wu Wei-Zhen, Pan Feng, Hong Nan, Deng Jie

机构信息

Jin Cheng, Yi Wang, Wei-Zhen Wu, Feng Pan, Nan Hong, Department of Radiology, Peking University People's Hospital, Beijing 100044, China.

出版信息

World J Gastroenterol. 2017 Mar 21;23(11):1990-2001. doi: 10.3748/wjg.v23.i11.1990.

AIM

To determine the role of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) magnetic resonance imaging (MRI) using a bi-exponential model in chemotherapy response evaluation in a gastric cancer mouse model.

METHODS

Mice bearing MKN-45 human gastric adenocarcinoma xenografts were divided into four treated groups (TG1, 2, 3 and 4, = 5 in each group) which received Fluorouracil and Calcium Folinate and a control group (CG, = 7). DW-MRI scans with 14 b-values (0-1500 s/mm) were performed before and after treatment on days 3, 7, 14 and 21. Fast diffusion component (presumably pseudo-perfusion) parameters including the fast diffusion coefficient (D*) and fraction volume (), slow diffusion coefficient (D) and the conventional apparent diffusion coefficients (ADC) were calculated by fitting the IVIM model to the measured DW signals. The median changes from the baseline to each post-treatment time point for each measurement (ΔADC, ΔD* and Δ) were calculated. The differences in the median changes between the two groups were compared using the mixed linear regression model by the restricted maximum likelihood method shown as z values. Histopathological analyses including Ki-67, CD31, TUNEL and H&E were conducted in conjunction with the MRI scans. The median percentage changes were compared with the histopathological analyses between the pre- and post-treatment for each measurement.

RESULTS

Compared with the control group, D* in the treated group decreased significantly (ΔD*% = -30%, -34% and -20%, with z = -5.40, -4.18 and -1.95. = 0.0001, 0.0001 and 0.0244) and increased significantly (Δ% = 93%, 113% and 181%, with z = 4.63, 5.52, and 2.12, = 0.001, 0.0001 and 0.0336) on day 3, 7 and 14, respectively. Increases in ADC in the treated group were higher than those in the control group on days 3 and 14 (z = 2.44 and 2.40, = 0.0147 and = 0.0164).

CONCLUSION

Fast diffusion measurements derived from the bi-exponential IVIM model may be more sensitive imaging biomarkers than ADC to assess chemotherapy response in gastric adenocarcinoma.

目的

利用双指数模型的体素内不相干运动（IVIM）扩散加权（DW）磁共振成像（MRI）确定其在胃癌小鼠模型化疗反应评估中的作用。

方法

将携带MKN-45人胃腺癌异种移植瘤的小鼠分为四个治疗组（TG1、TG2、TG3和TG4，每组n = 5），给予氟尿嘧啶和亚叶酸钙，以及一个对照组（CG，n = 7）。在治疗前以及治疗后第3、7、14和21天进行具有14个b值（0 - 1500 s/mm²）的DW-MRI扫描。通过将IVIM模型拟合到测量的DW信号来计算快速扩散成分（可能是伪灌注）参数，包括快速扩散系数（D*）和分数体积（f）、慢速扩散系数（D）以及传统的表观扩散系数（ADC）。计算每次测量从基线到每个治疗后时间点的中位数变化（ΔADC、ΔD*和Δf）。使用限制最大似然法的混合线性回归模型比较两组中位数变化的差异，以z值表示。结合MRI扫描进行包括Ki-67、CD31、TUNEL和苏木精-伊红（H&E）染色的组织病理学分析。比较每次测量治疗前后组织病理学分析的中位数百分比变化。

结果

与对照组相比，治疗组的D在第3、7和14天显著降低（ΔD% = -30%、-34%和-20%，z = -5.40、-4.18和-1.95，P = 0.0001、0.0001和0.0244），f在第3、7和14天分别显著增加（Δf% = 93%、113%和181%，z = 4.63、5.52和2.12，P = 0.001、0.0001和0.0336）。治疗组在第3天和第14天ADC的增加高于对照组（z = 2.44和2.40，P = 0.0147和P = 0.0164）。