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.

An Interpretable Deep Learning Framework for Discovery and Clinical Validation of Deep Radiomic Signatures in Tumor Classification

Imaging signatures are quantitative features extracted from medical images that provide clinically meaningful information for tumor diagnosis, characterization, prognosis, and treatment planning. Although deep learning has shown great potential for imaging signature discovery, its limited interpretability remains a major barrier to clinical adoption. Existing approaches often achieve high predictive performance but provide little biological insight into the identified signatures. We propose a unified framework for interpretable imaging signature discovery by integrating deep learning based segmentation, explainable classification, and radiomic analysis. A robust segmentation model is first used to accurately delineate tumors, followed by a Grad-CAM guided pipeline that identifies diagnostically important regions as candidate imaging signatures. A mutual information based adaptive thresholding strategy enables patient-specific signature extraction. The resulting signatures are validated using a downstream deep learning classification model, while radiomic features extracted from the signature regions are evaluated with traditional machine learning models and interpreted using SHAP to identify the most discriminative biomarkers. The proposed framework is evaluated on the public BUSI breast ultrasound, KiTS renal CT, and BraTS brain tumor datasets, as well as a private UF Health renal CT cohort. Compared with conventional whole-tumor radiomics, the proposed signature-based approach achieves improved discriminative performance while providing greater biological interpretability. By converting deep learning attention into reproducible quantitative imaging biomarkers, this framework offers an interpretable and reproducible solution for non-invasive tumor characterization and imaging biomarker discovery.

A Novel Machine Learning Approach for Central Nervous System Tumor Classification from DNA Methylation

NA methylation profiling has become a powerful approach for central nervous system (CNS) tumor classification, yet important challenges remain regarding cross-cohort transferability, methodological correctness, and robust multiclass evaluation. In this work, we propose a novel and methodologically rigorous machine-learning approach for methylation-based CNS tumor classification that combines Sparse Random Projection for dimensionality reduction with multinomial logistic regression for classification. We evaluate the proposed approach in the same general experimental setting established by a widely used reference classifier. On the 2,801-sample reference cohort, our method achieves a mean accuracy of 96\% under stratified 3-fold cross-validation. On the independent 1,104-sample clinical evaluation cohort, it reaches 86\% accuracy at the 91-class level and 93\% when predictions are evaluated at the methylation class family level. These results improve upon the corresponding state-of-the-art reference figures of 82\% class-level concordance and 88\% family-level concordance, yielding absolute gains of approximately 4 and 5 percentage points, respectively. This improvement is clinically relevant: in a diagnostic setting, a 5-point increase in correct tumor classification can directly affect cancer subtype assignment and, in turn, influence treatment selection and downstream clinical decision-making. Our results show that the proposed model, grounded in stronger methodological practice in machine learning, consistently outperforms the previous state of the art across evaluation settings and can materially improve the reliability of CNS tumor classification.