Intratumoral Heterogeneity of Fibrosarcoma Xenograft Models: Whole-Tumor Histogram Analysis of DWI and IVIM

Abstract

Rational and objective: To explore the correlations of histogram parameters from diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) with the heterogeneous features in a nude mouse model of fibrosarcoma.

Materials and methods: A total of 44 fibrosarcoma xenograft models were established by inoculating HT-1080 cells on the right thigh of mice and subjected tumors to DWI and IVIM imaging with 3.0 T MRI. Whole-tumor histogram parameters were calculated on apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Heterogeneous features, including necrosis rate, cell density, Ki-67 labeling index (LI), and microvascular density (MVD) were measured. Intraclass correlation coefficients (ICC), Pearson or Spearman correlation tests, and receiver operating characteristics (ROC) were performed.

Results: The 90th percentile, skewness and kurtosis of ADC and D histograms showed correlations with necrosis rate, and the highest correlation coefficient was found for D_90th (r = 0.485). ADC and D histogram parameters showed correlations with cell density and Ki-67 LI; D_90th showed the highest correlation coefficient with cell density (r = -0.504); and D_median showed the most significant correlation with Ki-67 LI (r = -0.525). D*_skewness, D*_kurtosis, D*_90th, f_mean, and f_median showed correlations with MVD. ADC_90th, ADC_skewness, ADC_kurtosis, D_90th, and D_skewness showed significant differences between the low necrosis and high necrosis groups, and the combination model showed the best diagnostic ability (AUC = 0.882), with 97% sensitivity, and 72.7% specificity.

Conclusion: Whole-tumor histogram parameters of DWI and IVIM were correlated with heterogeneous features in nude murine models of fibrosarcoma.

Keywords: Fibrosarcoma; Heterogeneous; Histogram; Magnetic resonance imaging; Mice.