Graph-Radiomic Learning (GrRAiL) Descriptor to Characterize Imaging Heterogeneity in Confounding Tumor Pathologies

A significant challenge in solid tumors is reliably distinguishing confounding pathologies from malignant neoplasms on routine imaging. While radiomics methods seek surrogate markers of lesion heterogeneity on CT/MRI, many aggregate features across the region of interest (ROI) and miss complex spatial relationships among varying intensity compositions. We present a new Graph-Radiomic Learning (GrRAiL) descriptor for characterizing intralesional heterogeneity (ILH) on clinical MRI scans. GrRAiL (1) identifies clusters of sub-regions using per-voxel radiomic measurements, then (2) computes graph-theoretic metrics to quantify spatial associations among clusters. The resulting weighted graphs encode higher-order spatial relationships within the ROI, aiming to reliably capture ILH and disambiguate confounding pathologies from malignancy. To assess efficacy and clinical feasibility, GrRAiL was evaluated in n=947 subjects spanning three use cases: differentiating tumor recurrence from radiation effects in glioblastoma (GBM; n=106) and brain metastasis (n=233), and stratifying pancreatic intraductal papillary mucinous neoplasms (IPMNs) into no+low vs high risk (n=608). In a multi-institutional setting, GrRAiL consistently outperformed state-of-the-art baselines - Graph Neural Networks (GNNs), textural radiomics, and intensity-graph analysis. In GBM, cross-validation (CV) and test accuracies for recurrence vs pseudo-progression were 89% and 78% with >10% test-accuracy gains over comparators. In brain metastasis, CV and test accuracies for recurrence vs radiation necrosis were 84% and 74% (>13% improvement). For IPMN risk stratification, CV and test accuracies were 84% and 75%, showing >10% improvement.