Generative T2-FLAIR mismatch sign in glioma: Optimizing phenotype augmentation for isocitrate dehydrogenase mutation prediction

This study investigated the effects of feature augmentation, which uses generated images with specific imaging features, on the performance of isocitrate dehydrogenase (IDH) mutation prediction models in gliomas. A total of 598 patients were included from our institution (310 training, 152 internal test) and the Cancer Genome Atlas (136 external test). Score-based diffusion models were used to generate T2-weighted, FLAIR, and contrast-enhanced T1-weighted image triplets. Three neuroradiologists independently assessed visual Turing tests and various morphological features. Multivariable logistic regression models were developed using real images, random augmented data, and feature-augmented datasets. While random augmentation yielded models with AUCs comparable to real image-based models, it led to reduced specificity, particularly in the external test set (specificity: 83.2% vs. 73.0%, P  = .013). In contrast, feature-augmented models maintained stable diagnostic performance; however, when more than 70% of training images included synthetic T2-FLAIR mismatch signs, AUC decreased in the external test set (AUC: 0.905–0.906 for ≤ 70%; 0.902–0.876 for ≥ 80%). These findings highlight the value of phenotype-specific augmentation for IDH prediction, while emphasizing the need to optimize augmentation proportion to avoid performance degradation.