[Evaluation of tumor vascular normalization in colorectal cancer mouse mode induced by recombinant human endostatin by intravoxel incoherent motion diffusion-weighted magnetic resonance imaging].

Objective To evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES). Methods The CT26 colorectal cancer xenograft model of BALB/c mice were established and divided into rhES group and control group, with 20 mice in each group. The mice of rhES group were intravenously injected with rhES 5 mg·kg-1·d-1 once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9% saline. 5 mice of rhES group and control group were randomly selected to perform IVIM-DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM-DWI were recorded, including true diffusion coefficient(D), pseudo-diffusion coefficient (D*) and perfusion fraction (f). Meanwhile, microvessel density (MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results The tumor volumes of control group and rhES group before treatment were (154.42±24.65) mm3 and (174.24±28.27)mm3, respectively, without statistically significant difference (P=0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group (all P 0.05). The D* values of the rhES group were (10.940±2.834)×10-3mm2/s and (12.940±2.801)×10-3mm2/s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10-3mm2/s and (7.898±1.603)×10-3mm2/s of control group (P<0.05). Moreover, compared with control group, the D* value of rhES group was significantly lower in day 12 (6.848±1.460)×10-3mm2/s vs (9.950±2.596)×10-3mm2/s, (P<0.05). The f value of rhES group in day 8 was (0.226±0.021)%, significantly higher than (0.178±0.016)% of control group (P<0.01). The MVD of rhES group was significantly lower than that of control group (P<0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment (all P<0.05). In addition, we found D* value of IVIM-DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.354, r=0.555, r=0.559, all P<0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion (r=-0.391, r=0.538, r=0.315, all P<0.05). Conclusions IVIM-DWI MRI can effectively evaluate the vascular normalization in rhES-induced CT26 colorectal tumor.The parameters D* and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time. Key words: Colorectal neoplasms; Intravoxel incoherent motion; Diffusion magnetic resonance imaging; Vascular normalization; Recombinant human endostatin; Angiogenesis