An ai-based coordinate system elucidates radiogenomic heterogeneity of glioblastoma via deep learning and manifold embeddings

Abstract PURPOSE There is evidence that molecular heterogeneity of glioblastoma is associated with heterogeneity of MR imaging signatures. Modern machine learning models, such as deep neural networks, provide a tool for capturing such complex relationships in high-dimensional datasets. This study leverages recent advances in visualizing neural networks to construct a radiogenomics coordinate system whose axes reflect the expression of imaging signatures of genetic mutations commonly found in glioblastoma. METHODS Multi-parametric MRI (mpMRI) scans (T1, T1-Gd, T2, T2-FLAIR, DSC, DTI) of 254 subjects with glioblastoma were retrospectively collected. Radiomics features, including histograms, morphologic and textural descriptors, were derived. Genetic markers were obtained through next generation sequencing (NGS) panel. A multi-label classification deep neural network was trained for predicting mutation status in key driver genes, EGFR, PTEN, NF1, TP53 and RB1. We utilized a nonlinear manifold learning method called Intensive Principal Component Analysis (InPCA), to visualize the output probability distributions from the trained model. The first three principal components (PCs) were selected for constructing the coordinate system. RESULTS The axes derived from InPCA analysis were associated with molecular pathways known to be implicated in glioblastoma: (1) Increasing values of PC1 were associated with primary involvement of P53 then RB1 then MAPK then RTK/PI3K; (2) Increasing values of PC2 were associated with primary involvement of RTK then RB1/P53/MAPK then PI3K; (3) Increasing values of PC3 were associated with primary involvement of MAPK then RB1/P53/RTK/PI3K. Imaging features significantly associated with each of three PCs (p< 0.05) were identified by Pearson correlation analysis. CONCLUSION Deep learning followed by nonlinear manifold embedding identifies a radiogenomics coordinate system spanned by three components which were associated with different molecular pathways of glioblastoma. The heterogeneity of radiogenomic signatures captured by this coordinate system offers in vivo biomarkers of the molecular heterogeneity of glioblastoma.