Enhancing PET/CT Radiomics Robustness Through Graph Signal Processing

Background/Objectives: Prostate cancer (PCa) frequently metastasizes to bone, leading to severe clinical complications and reduced quality of life. Accurate and robust imaging-based characterization of bone lesions is therefore critical for diagnosis and treatment planning. Radiomics has emerged as a powerful tool for extracting quantitative information from medical images; however, classical radiomics features are often affected by inter-scanner variability, segmentation dependence, and limited ability to describe lesions with complex biological heterogeneity. This study aims to introduce a translational graph-based radiomics approach designed to extract novel quantitative descriptors with improved robustness and clinical reliability. Methods: A graph representation was derived from segmented Positron Emission Tomography/Computed Tomography (PET/CT) bone lesions by generating a point cloud followed by Delaunay triangulation to preserve geometric information. Graph signal processing techniques were applied to extract three classes of features: orientation, connectivity, and transform-based descriptors. The dataset included PET/CT scans from 50 PCa patients acquired using two different scanners, comprising 92 bone lesions classified as benign or malignant. Correlation analysis with classical radiomics features was performed to assess information redundancy. Robustness against batch effects and segmentation variability was evaluated. Classification performance was tested using Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) models based on proposed features, classical features, and their combination. Results: The proposed features captured non-redundant information compared to classical radiomics and demonstrated superior robustness to scanner-related batch effects and segmentation variability. In classification tasks, models using the proposed features consistently outperformed those based on classical radiomics. Using LDA, the proposed features achieved a mean balanced accuracy of 69.68% and a mean Area Under the Curve (AUC) of 72.14%. With SVM, they achieved a mean balanced accuracy of 65.16% and a mean AUC of 66.49%, exceeding the performance of classical and combined feature sets. Conclusions: This study presents a translational graph-based radiomics framework that extends beyond conventional methodologies, improving robustness and diagnostic performance. The proposed approach shows promise as an integrative tool for more reliable PET/CT-based characterization of bone lesions in prostate cancer.