An Interpretable Deep Learning Framework for Discovery and Clinical Validation of Deep Radiomic Signatures in Tumor Classification
For clinicians and researchers in medical imaging, this framework addresses the interpretability barrier of deep learning in imaging signature discovery, enabling more trustworthy and biologically meaningful tumor characterization.
The paper proposes an interpretable deep learning framework that integrates segmentation, explainable classification, and radiomic analysis to discover and validate imaging signatures for tumor classification. On three public and one private dataset, the signature-based approach outperforms conventional whole-tumor radiomics in discriminative performance while providing greater biological interpretability.
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.