Exploratory quantitative magnetic resonance imaging characterization of histopathologic subtype heterogeneity in...

Osteosarcoma is the most common primary malignant bone tumor in children and young adults and demonstrates substantial histopathologic heterogeneity that complicates diagnosis and treatment monitoring. Conventional imaging and biopsy may not adequately reflect whole-tumor biology because of spatial sampling limitations. Multiparametric magnetic resonance imaging (MRI), including dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI), provides quantitative biomarkers related to tumor vascularity and cellularity. The aim of this study was to evaluate the association between quantitative DCE-MRI parameters and apparent diffusion coefficient (ADC) values across osteosarcoma subtypes and to explore their role in reflecting histopathologic heterogeneity.

This retrospective exploratory study included 43 patients with histopathologically confirmed osteosarcoma who underwent pre-treatment 3.0-T MRI, including DCE-MRI and DWI, between January 2023 and February 2025. The cohort consisted of 17 osteoblastic, 9 fibroblastic, 6 chondroblastic, 5 giant cell-rich, 5 telangiectatic, and 1 extraskeletal osteosarcoma cases. Quantitative pharmacokinetic parameters (K^trans, K_ep, and V_e) were derived using the Tofts model, while ADC values were obtained from diffusion-weighted sequences. Inter-subtype differences were evaluated using the Kruskal-Wallis test and Dunn-Bonferroni post hoc analyses. Receiver operating characteristic (ROC) analysis and multivariable logistic regression were performed to assess diagnostic performance.

K^trans demonstrated the strongest discriminatory performance across osteosarcoma subtypes (H = 13.852, p = 0.017), with significantly higher values observed in chondroblastic compared with telangiectatic tumors. ROC analysis demonstrated good diagnostic performance of K^trans in identifying osteoblastic (area under the curve [AUC] = 0.806, 95% confidence interval [CI]: 0.652-0.960, p = 0.021) and chondroblastic (AUC = 0.775, 95% CI: 0.611-0.939, p = 0.033) subtypes. ADC values provided complementary information regarding tumor cellularity but demonstrated less consistent discriminatory performance. K_ep and V_e did not show statistically significant differences across subtypes.

Quantitative DCE-MRI parameters, particularly K^trans, demonstrated significant associations with osteosarcoma subtype heterogeneity and may reflect differences in tumor vascular permeability. Combined diffusion and perfusion imaging may provide complementary information for non-invasive characterization of osteosarcoma. However, these findings should be interpreted cautiously because of the exploratory design and limited subgroup sample sizes, and further validation in larger prospective multicenter studies is required.