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.
Non-invasive prediction of Gleason Grade Group (GGG) in prostate cancer using multiparametric MRI (mpMRI) is clinically vital for reducing unnecessary biopsies. Existing GGG prediction methods face two major limitations. First, they often overlook non-image information critical for GGG prediction, including age, prostate-specific antigen (PSA), and expert priors embedded in radiology reports. Second, they tend to oversimplify GGG as flat categorical labels, failing to account for its intrinsic hierarchy of primary and secondary Gleason patterns. To this end, we propose a novel Knowledge-Driven Ordinal-Aware Learning (KOAL) framework with three synergistic modules. Specifically, the Clinical-Context Modulation (CCM) module uses clinical variables (e.g., age and PSA) to dynamically modulate discriminative image representations. The Knowledge-Guided Prototype Alignment (KGPA) module leverages an LLM to extract group-specific expert knowledge from training radiology reports and clinical guidelines, producing offline semantic anchors describing grade-specific radiological findings without requiring patient-specific reports at inference. Through prototype contrastive alignment, patient-specific mpMRI representations are matched with these anchors to promote pathology-aligned representation learning. The Hierarchical Ordinal-aware Constraints (HOC) module decouples primary and secondary Gleason pattern prediction and maps their probabilistic outputs to GGG via a Differentiable Bio-logic Mapping Layer (DBML), ensuring pathological grading consistency. Experiments on public PI-CAI and in-house datasets demonstrate that KOAL outperforms state-of-the-art methods. Code is available at: https://github.com/Gother-GZ/KOAL.