Fractal Dimension of High-Risk Neuroblastoma Vascularity in MRI Is Associated with Chemotherapy Response and Event-Free Survival

Purpose To assess therapeutic and prognostic implications of perfusion characterization by fractal analysis using routine MRI in high-risk primary neuroblastomas and to establish a pathophysiologic connection between vascularity phenotype, perfusion imaging characteristics, and treatment response. Materials and Methods In a retrospective cohort study across 30 centers, MRI data of patients with high-risk neuroblastoma (June 2005-February 2021) were collected at the time point of diagnosis (TP1) and after induction chemotherapy before surgery (TP2), with data split into separate discovery (single-center) and validation cohorts (29 centers). Fractal analysis was performed on contrast-enhanced, fat-saturated, T1-weighted sequences at both time points to obtain voxel-wise local fractal dimension (FD) maps for predicting volumetric tumor response. The association of global FD with event-free survival (EFS) was assessed using a Cox proportional hazards model. Additionally, FD was calculated from CD34-stained endothelium in selected histologic tumor samples. Accuracy of response prediction, prognostic value for EFS, and correlation between FD of immunohistochemical vascularity and MRI-derived perfusion were also evaluated. Results In 73 patients (median age, 3 years [IQR, 3]; 39 male patients; discovery cohort, <i>n</i> = 36; validation cohort, <i>n</i> = 37), local FD maps helped predict volumetric tumor response to induction chemotherapy between TP1 and TP2 with good accuracy (root mean squared error, 47.78 mL; <i>R</i>² = 0.94; <i>P</i> < .001), visualizing intratumor high perfusion complexity in areas with low response potential. In multivariate Cox proportional hazards modeling, <i>MYCN</i> status (hazard ratio, 2.30; 95% CI: 1.16, 4.55; <i>P</i> = .017) and global FD at TP2 (hazard ratio, 0.65; 95% CI: 0.47, 0.88; <i>P</i> = .006) were significantly associated with EFS. Complexity of both CD34-immunohistochemical microvascularity (1.23 ± 0.09 [SD] to 1.44 ± 0.07, <i>P</i> < .001) and MRI perfusion (3.40 ± 0.04 to 3.53 ± 0.07, <i>P</i> < .001) increased throughout induction chemotherapy. Conclusion Fractal analysis of MRI-derived perfusion complexity was associated with spatial heterogeneity of chemotherapy response and stratified prognosis in <i>MYCN</i> nonamplified high-risk neuroblastoma, supporting its potential as an imaging biomarker linked to microvascular architecture. German Clinical Trial Registry: DRKS00023442 <b>Keywords:</b> Pediatrics, MR-Imaging, Nervous-Peripheral, Fractal Analysis, Tissue Characterization, Tumor Response <i>Supplemental material is available for this article.</i> © RSNA, 2025.