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Original Article
A study of IVIM-DWI in the treatment of ultra-early changes of transplanted tumor in nude mice
XU Xiao-shuang  MA Rong  ZHANG Dong  SHI Chang-zheng  XIA Ming-han  XING Hui-jie  CHEN Min-feng  LUO Liang-ping 

DOI:10.12015/issn.1674-8034.2017.10.009.


[Abstract] Objective: To monitor the treatment of ultra-early changes in liver subcutaneous transplanted tumor in nude mice with new vascular disrupting agent, A64, using the IVIM-DWI technique and to investigate the correlation between the ultra-early pathological and physiological changes in tumor and the IVIM parameters after A64 treatment.Materials and Methods: Twenty-two liver subcutaneous transplanted tumor models of nude mice were established, and randomly divided into MR examination group and parallel pathology group, and injected with A64 (2 μmol/kg) from the caudal vein of nude mice. The MR examination group (n=10) received the intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) at five time points: baseline time, at 1 h, 2 h, 4 h and 24 h after injection; the D, D* and f values were measured dynamically; and all mice were executed at 24 h to obtain the tumor samples. 3 mice in the parallel pathology group (n=12) were executed at the baseline time, 1 h, 2 h, 4 h and 24 h after injection, respectively, to obtain the tumor sample at the corresponding time point, among which the 3 mice at 24 h were randomly selected from all the executed mice in the experimental group at 24 h. The tumor samples were treated with the routine HE and CD31 immunohistochemical staining.Results: Compared with that at the baseline level, D value continued to decline at 1 h and 2 h, began to rise at 4 h and returned to the baseline level at 24 h; D* and f values continued to decline within 4 h, and rose at 24 h. But the change in f value was not as significant as that in D* value. At 1-2 h after injection of A64, the shape abnormality of tumor vessels, lumen stenosis and occlusion, destruction and tumor necrosis occurred, leading to the decreased number of tumor vessels and proliferated tumor angiogenesis, and the value returned to over baseline level at 4 h.The variation trend of D* and f values was similar to that of CD31-IOD. There were statistically significant differences (P=0.000,0.000,0.005, 0.000) in the D, D*, f and CD31 integrated option density (CD31-IOD) at each time point.Conclusion: Among the IVIM-DWI parameters, D, D* and f can dynamically monitor and quantitatively evaluate the ultra-early effect of A64 on liver subcutaneous transplanted tumor in nude mice. And the changes in D, D* and f values are closely related to the pathology and CD31.
[Keywords] Vascular disruping agent;Intravoxel incoherent motion;Magnetic resonance imaging;Rats;Animal experimentation

XU Xiao-shuang Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China

MA Rong Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China

ZHANG Dong Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China

SHI Chang-zheng Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China

XIA Ming-han Department of Pathology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China

XING Hui-jie Institute of Laboratory Animal, Jinan University, Guangzhou 510632, China

CHEN Min-feng College of Pharmacy, Jinan University, Guangzhou 510632, China

LUO Liang-ping* Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China

*Correspondence to: Luo LP, E-mail: tluolp@jnu.edu.cn

Conflicts of interest   None.

Received  2017-07-04
Accepted  2017-09-06
DOI: 10.12015/issn.1674-8034.2017.10.009
DOI:10.12015/issn.1674-8034.2017.10.009.

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