# Apparent Diffusion Coefficient and Native T1 Mapping Histogram Analyses Reveal Tumor Proliferation and Microenvironment in Neuroblastoma Xenografts

## TL;DR

This study shows that MRI techniques can reveal tumor growth and environment in neuroblastoma, offering non-invasive insights for treatment.

## Contribution

The study demonstrates that ADC and T1 mapping can capture complementary aspects of neuroblastoma biology non-invasively.

## Key findings

- ADC values were negatively correlated with tumor cell proliferation after FDR correction.
- T1 mapping features were positively correlated with collagen content after FDR correction.
- Combining ADC and T1 mapping provides complementary information about tumor biology.

## Abstract

Neuroblastoma is a common childhood cancer, and understanding how it grows and interacts with its surrounding environment is important for developing better treatments. Magnetic resonance imaging (MRI) can provide detailed information about tumors without surgery, but it is still unclear which MRI measurements best reflect tumor activity and structure. In high-risk neuroblastoma, upfront surgery is rarely performed, and neoadjuvant chemotherapy is often required, making direct correlation between imaging and biopsy challenging. In this exploratory preclinical study, we used advanced MRI techniques, including apparent diffusion coefficient (ADC) and native T1 mapping, in a mouse model of neuroblastoma to explore how these imaging measures relate to tumor proliferation and microenvironment. We found that ADC values were negatively related to tumor cell growth, whereas T1 mapping features were positively related to collagen content after false discovery rate correction. These findings provide preliminary evidence that combining ADC and T1 mapping can capture complementary aspects of neuroblastoma biology. The complementary information derived from ADC and T1 mapping may contribute to noninvasive assessment of tumor aggressiveness, extracellular remodeling, and risk stratification, providing a methodological foundation for future diagnostic and prognostic applications in clinical neuroblastoma imaging.

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 ADC10Percentile (r = −0.397, adjusted p = 0.032), ADC90Percentile (r = −0.394, adjusted p = 0.032), ADCmaximum (r = −0.362, adjusted p = 0.048), ADCmean (r = −0.421, adjusted p = 0.032), ADCmedian (r = −0.422, adjusted p = 0.032), ADCminimum (r = −0.390, adjusted p = 0.032), and ADCrootmeansquared (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.