Functional MRI and Tumor Vasculature Correlation in Ewing Sarcoma Xenografts: A Prospective Study Based on MRI-Pathology Co-Alignment.

Abstract

Background: Limited studies have evaluated vascular markers of Ewing sarcoma (ES) using MRI.

Purpose: To explore the correlation between tumor vascular markers and MRI perfusion parameters in ES xenografts based on MRI-pathology co-alignment.

Study type: Prospective.

Animal model: Thirty-four ES xenograft models were established in female athymic nude mice using the human-derived A673 cell line.

Field strength/sequence: 3 T MRI, T₁-weighted (T1w) with fast spin echo sequence, T2w with fast recovery fast spin echo sequence, intravoxel incoherent motion (IVIM) with echo-planar diffusion-weighted sequence, and dynamic contrast-enhanced MRI (DCE-MRI) with the liver acquisition with volume acceleration sequence.

Assessment: IVIM parameters (D, D*, and f), DCE-MRI semiquantitative parameters (maximum slope of increase [MSI], contrast-enhancement ratio [CER], and initial area under the gadolinium curve [iAUGC]), and DCE-MRI quantitative parameters (K_trans, K_ep, and V_e). The expression of vascular endothelial growth factor (VEGF), microvessel density (MVD), and vascular mimicry (VM) was evaluated by immunohistochemical staining.

Statistical tests: Intraclass correlation coefficient (ICC), bootstrap resampling, Fisher's Z transformation, Pearson or Spearman correlation analysis, receiver operating characteristic curve (ROC) analysis, and DeLong's test. p < 0.05 was considered statistically significant.

Results: K_trans, K_ep, f, and D* values showed significant correlations with VEGF (r = 0.697, 0.630, 0.781, 0.695, respectively). D*, f, K_trans, MSI, and CER values showed significant correlations with MVD (r = 0.42, 0.554, 0.486, 0.461, 0.416, respectively). D and f values showed significant correlations with VM (r = -0.552, 0.384, respectively). K_trans, f, D*, and K_ep values were good diagnostics in distinguishing between high- and low-expression groups of VEGF (AUC = 0.833-0.954). D* and D values were good diagnostics in distinguishing between high- and low-expression groups of MVD and VM (AUC = 0.727, 0.739, respectively).

Data conclusion: IVIM and DCE-MRI can be utilized to assess tumor vasculature in ES xenografts.

Evidence level: 1.

Technical efficacy: Stage 3.