Brief Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 21, 2013; 19(47): 9092-9103
Published online Dec 21, 2013. doi: 10.3748/wjg.v19.i47.9092
Separate calculation of DW-MRI in assessing therapeutic effect in liver tumors in rats
Feng Chen, Frederik De Keyzer, Yuan-Bo Feng, Marlein Miranda Cona, Jie Yu, Guy Marchal, Raymond Oyen, Yi-Cheng Ni
Feng Chen, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Feng Chen, Frederik De Keyzer, Yuan-Bo Feng, Marlein Miranda Cona, Jie Yu, Guy Marchal, Raymond Oyen, Yi-Cheng Ni, Theragnostic Laboratory, Department of Imaging and Pathology, University Hospital, University of Leuven, Herestraat 49, Bus 7003, 3000 Leuven, Belgium
Author contributions: All the authors substantially contributed to conception and design, acquisition of data, or analysis and interpretation of data, drafting the article or revising it critically for important intellectual content, and final approval of the version to be published; Chen F, Feng YB, Yu J and Ni YC conducted animal experiments; Chen F and Keyzer FD performed statistical analyses.
Supported by National Natural Science Foundation of China, No. 30670603
Correspondence to: Feng Chen, MD, PhD, Deputy Director, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. chenfengbe@aliyun.com
Telephone: +86-571-87236587 Fax: +86-571-87236587
Received: July 31, 2013
Revised: October 19, 2013
Accepted: November 3, 2013
Published online: December 21, 2013
Processing time: 173 Days and 18.7 Hours
Abstract

AIM: To explore whether the antitumor effect of a vascular disrupting agent (VDA) would be enhanced by combining with an antiangiogenic agent, and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging (DW-MRI).

METHODS: Thirty-seven rats with implanted liver tumors were randomized into the following three groups: (1) ZD6126, a kind of VDA; (2) ZDTHA, ZD6126 in combination with an antiangiogenic, thalidomide; and (3) control. Morphological DW-MRI were performed and quantified before, 4 h and 2 d after treatment. The apparent diffusion coefficient (ADC) values were calculated separately for low b values (ADClow), high b values (ADChigh) and all b values (ADCall). The tissue perfusion contribution, ADCperf, was calculated as ADClow-ADChigh. Imaging findings were finally verified by histopathology.

RESULTS: The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis. In addition to delaying tumor growth, ZDTHA caused tumor necrosis in an additive manner, which was verified by HE staining. Although both ADChigh and ADCall in the ZD6126 and ZDTHA groups were significantly higher compared to those in the control group on day 2, the entire tumor ADChigh of ZDTHA was even higher than that of ZD6126, but the significant difference was not observed for ADCall between ZDTHA and ZD6126. This indicated that the perfusion insensitive ADChigh values calculated from high b value images performed significantly better than ADCall for the monitoring of tumor necrosis on day 2. The perfusion sensitive ADCperf derived from ADClow by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126, compared to the ADClow at 4 h. The ADCperf could provide valuable perfusion information from DW-MRI data.

CONCLUSION: The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126 and thalidomide for solid tumors.

Keywords: Diffusion weighted imaging; Magnetic resonance imaging; Therapeutic assessment; Liver tumor; Rats; Vascular disrupting agent; Antiangiogenic agent; Animal model; Rodents

Core tip: The combination therapy with ZD6126 and thalidomide significantly delayed liver tumor growth due to synergistic effects by inducing cumulative tumor necrosis in rodents. The apparent diffusion coefficient (ADC)high performed significantly better than ADCall for the monitoring of tumor necrosis on day 2. The ADCperf could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126, compared to the ADClow. The ADCperf could provide valuable perfusion information from diffusion weighted magnetic resonance imaging data.