A correlation study between intravoxel incoherent motion MRI and histopathology in a hepatocellular carcinoma tumor model

Objective: To explore the correlations between intravoxel incoherent motion (IVIM) parameters measured at different time points and histopathological markers in an orthotopic xenograft hepatocellular carcinoma (HCC) nude mice model. Methods: A total of 40 HCC orthotopic bearing mouse models were established. When they grew to 21 days, 10 HCC-bearing mice were randomly selected as the baseline group (Group A) by a numeric table method. Then the rest mice were randomly selected on the 28 th day, 35 th day, and 42 nd day of the growth by using the same method, 10 each for B, C, and D groups, respectively. All mice underwent MR IVIM study and apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D^*) and perfusion fraction (f) were measured. After the MRI scanning, the tumors were removed for pathological examination. The necrosis score (NF), tumor size and microvessel density (MVD) were calculated. The IVIM parameters were compared among these 4 groups by Kruskal-Wallis H test and the correlations between these IVIM parameters and histological features were studied with Spearman rank correlation test. Results: One tumor in each of C and D groups was excluded because f values of IVIM were close to zero. There were significant differences found in ADC and D among all the 4 groups (P < 0.05). However, no difference was found in D^* and f (P > 0.05). Compared with the baseline (group A), ADC decreased significantly at 7 and 14 days, whilst D decreased significantly at 7 days. The differences in tumor size, MVD and NF between the 4 groups were statistically significant. Compared with the baseline, the tumor size and NF significantly increased at 7, 14 and 21 days, and MVD increased at 14 and 21 days. Significantly positive correlations were demonstrated between ADC and MVD, NF (r = 0.461 and 0.442, P < 0.05), between D and MVD, NF (r = 0.568 and 0.519, P < 0.05) after exclusion of the data from the baseline. The parameter f from all the time points including the baseline was positively correlated with histological MVD and NF (r = 0.590 and 0.458, P < 0.05). Conclusion: IVIM parameters may reflect the intratumoral vascularity, tumor cell proliferation and necrosis of HCC, and they are correlated with the pathological indicators. (authors)