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Objective To investigate the feasibility of magnetic resonance (MR) diffusion weighted imaging (DWI) for evaluation of radiotherapeutic effects on rabbit VX2 tumor model.Methods Sixteen New Zealand white rabbits received a subcutaneous implantation of VX2 tumor cdl suspension 0.5 mL (4× 107cells/mL) in their right thighs to set up tumor model. And 2 weeks later they were randomly divided into therapy group (Group T, n = 10) and control group (Group C, n = 6). Group T received radiotherapy at a single dose of 10 Gy. MR imaging (MRI) scan including short TI inversion recovery echo-planar imaging DWI, T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) sequences were performed 1 day prior to as well as 1 day, 2 days, 3 days and 7 days after radiotherapy. Group C received only MRI scan at the same time points without any treatment. MRI appearance on T2WI, T1WI, and DWI images was compared and tumor volume was calculated. Apparent diffusion coefficient (ADC) values of the tumor were evaluated in all cases. HE staining was used for pathological study.Results Necrosis (n = 8) and hemorrhage (n = 2) were seen gradually on T2WI and T1WI images of Group T after time point of day 2 after irradiation. In Group C, no obvious necrosis was found until day 7. There was no significant difference in tumor volume between the two groups before radiotherapy. After radiotherapy, tumors in Group T showed a gradual growth but not as obvious as Group C. There was a significant difference in tumor volume between the two groups from day 2 on (P < 0.05). ADC value changed dramatically right from the 1st day after radio-therapy in Group T [(0.99 ± 0.15) ×10-3 mm2/s for 1 day before radiotherapy, (1.23 ± 0.08) ×10-3 , (1.45 ± 0.07) ×10-3 , (1.63 ± 0.06) ×10-3 , and (2.02 ± 0.18) ×10-3 mm2/s for day 1, 2, 3, and 7]; and ADC value had no significant changes after radiotherapy in Group C except day 7 [(1.07 ± 0.08) ×10-3 mm2/s for 1 day before radiotherapy, (1.03 ± 0.04) ×10-3, (1.05 ± 0.02) ×10-3, (1.05 ± 0.05)×10-3 , and (0.95 ± 0.07)×10-3 mm2/s for day 1, 2, 3, and 7]. There was significant difference in ADC value between the two groups for each time point after radiotherapy (P < 0.01). Pathological study showed that the number of viable tumor cells in Group T decreased 1 day after radiotherapy, and the inflammatory cell infiltration was marked and almost all viable tumor cells disappeared by day 7 after radiotherapy. Conclusions DWI is a new promising technique for monitoring radiotherapy outcomes. ADC value may give a prior clue on physiological changes of radiotherapy before routine MRI could tell.