Unveiling the biological side of PET-derived biomarkers: a simulation-based approach applied to PDAC assessment.

Purpose Radiomics has revolutionized clinical research by enabling objective measurements of imaging-derived biomarkers. However, the true potential of radiomics necessitates a comprehensive understanding of the biological basis of extracted features to serve as a clinical decision support. In this work, we propose an end-to-end framework for the in silico simulation of [18F]FLT PET imaging process in Pancreatic Ductal Adenocarcinoma, accounting for the biological characterization of tissues (including perfusion and fibrosis) on tracer delivery. We thus establish a direct association between radiomics features and the underlying biological properties of tissues.Methods We considered 4 immunohistochemically stained Whole Slide Images of pancreatic tissue of one healthy control and three patients with PDAC and/or precursor lesions. From marker-specific images, tissue-depending diffusivity properties were estimated and computational domains were built to simulate the [18F]FLT spatial-temporal uptake exploiting Partial Differential Equations and Finite Elements Method. Consequently, we simulated the imaging process obtaining surrogated PET images for the considered patients, and we performed image-derived features extraction from PET images to be mapped with biological properties via correlation estimation.Results The framework captured the phenotypic differences and generated Time Activity Curves reflecting the underlying tissue composition. Image-derived biomarkers were ranked in view of their association with biological characteristics of the tissue, unveiling their molecular correlative. Moreover, we showed that the proposed pipeline could serve as a digital phantom to optimize the image acquisition for lesion detection.Conclusions This innovative framework holds the potential to enhance interpretability and reliability of radiomics, fostering the adoption in personalized nuclear medicine and patient care.