Diffusion tensor imaging‐based machine learning for IDH wild‐type glioblastoma stratification to reveal the biological underpinning of radiomic features

INTRODUCTION: This study addresses the lack of systematic investigation into the prognostic value of hand‐crafted radiomic features derived from diffusion tensor imaging (DTI) in isocitrate dehydrogenase (IDH) wild‐type glioblastoma (GBM), as well as the limited understanding of the biological interpretation of individual DTI radiomic features and metrics. AIMS: To develop and validate a DTI‐based radiomic model for predicting prognosis in patients with IDH wild‐type GBM and reveal the biological underpinning of individual DTI radiomic features and metrics. RESULTS: The DTI‐based radiomic signature was an independent prognostic factor (p < 0.001). Incorporating the radiomic signature into a clinical model resulted in a radiomic‐clinical nomogram that predicted survival better than either the radiomic model or clinical model alone, with a better calibration and classification accuracy. Four categories of pathways (synapse, proliferation, DNA damage response, and complex cellular functions) were significantly correlated with the DTI‐based radiomic features and DTI metrics. CONCLUSION: The prognostic radiomic features derived from DTI are driven by distinct pathways involved in synapse, proliferation, DNA damage response, and complex cellular functions of GBM.