Heterogeneity-Aware Deep Learning for Tumour Classification from Multiparametric MRI

Intra-tumoural heterogeneity (ITH) reflects spatial variation in tumour biology and is an important determinant of tumour behaviour, prognosis, and treatment response. Radiomics and deep learning have shown promise for tumour classification from multiparametric MRI (mp-MRI), but radiomics relies on handcrafted features, while most deep learning methods use whole-tumour representations or manually defined sub-regions, limiting scalable modelling of tumour heterogeneity. We propose a Heterogeneity-Aware Deep Learning Classification (HA-DLC) framework that explicitly models imaging-derived tumour sub-regions for lesion-type diagnosis and molecular-status prediction. HA-DLC consists of: (1) a Heterogeneous Sub-region Generation (HSG) module that produces initial pseudo-labelled sub-regions via unsupervised clustering, followed by Cross-Patient Sub-region Alignment (CPSA), which maps cluster-derived regions to a shared label space using soft assignments; and (2) a Dual-Stream Feature Extraction (DSFE) module that integrates local heterogeneity-aware features with global tumour representations. Given the initial clustering masks, CPSA, segmentation, feature extraction, and classification are jointly optimized end-to-end using soft-target segmentation and classification objectives. We evaluate HA-DLC on the LLD-MMRI2023 liver lesion dataset and the RSNA-ASNR-MICCAI 2021 Radiogenomic Brain Tumour dataset. HA-DLC consistently outperforms state-of-the-art radiomics and deep learning baselines, demonstrating the value of cross-patient sub-region alignment and dual-stream heterogeneity modelling for tumour classification from mp-MRI.