Apparent Diffusion Coefficient and Native T1 Mapping Histogram Analyses Reveal Tumor Proliferation and...

Objectives: This exploratory preclinical study aimed to compare the correlations of apparent diffusion coefficient (ADC) and native T1 mapping histogram features with tumor cell proliferation, microvessel density (MVD), and extracellular matrix composition in neuroblastoma xenografts. Methods: Neuroblastoma xenografts (n = 42) were established by subcutaneously injecting three MYCN-amplified/non-amplified human neuroblastoma cell lines (IMR-32, SK-N-BE(2), and SH-SY5Y; n = 14 per group) into female immunodeficient BALB/c-nude mice. Once tumors reached a diameter within the range of 12-15 mm, native T1 mapping and diffusion-weighted imaging were performed using a 3.0T clinical MRI scanner. Tumor cell proliferation and MVD were assessed via immunohistochemical Ki-67 staining and CD31 staining, respectively. Collagen fibers were visualized using Masson staining to calculate the collagen volume fraction (CVF). Pearson correlation coefficients with false discovery rate (FDR) correction were used to evaluate their associations. Results: Significant negative correlations were observed between Ki-67 expression and multiple ADC values after FDR correction, including ADC_10Percentile (r = -0.397, adjusted p = 0.032), ADC_90Percentile (r = -0.394, adjusted p = 0.032), ADC_maximum (r = -0.362, adjusted p = 0.048), ADC_mean (r = -0.421, adjusted p = 0.032), ADC_median (r = -0.422, adjusted p = 0.032), ADC_minimum (r = -0.390, adjusted p = 0.032), and ADC_{rootmeansquared} (r = -0.419, adjusted p = 0.032). In contrast, multiple T1 mapping features showed significant positive correlations with CVF (adjusted p < 0.05). Conclusions: ADC and T1 mapping provide complementary insights into tumor proliferation and extracellular matrix composition in neuroblastoma. These preclinical findings support further research to validate their potential clinical utility.