Generalizing imaging biomarker repeatability studies using Bayesian inference: Applications in detecting heterogeneous treatment response in whole-body diffusion-weighted MRI of metastatic prostate cancer

The assessment of imaging biomarkers is critical for advancing precision medicine and improving disease characterization. Despite the availability of methods to derive disease heterogeneity metrics in imaging studies, a robust framework for evaluating measurement uncertainty remains underdeveloped. To address this gap, we propose a novel Bayesian framework to assess the precision of disease heterogeneity measures in biomarker studies. Our approach extends traditional methods for evaluating biomarker precision by providing greater flexibility in statistical assumptions and enabling the analysis of biomarkers beyond univariate or multivariate normally-distributed variables. Using Hamiltonian Monte Carlo sampling, the framework supports both, for example, normally-distributed and Dirichlet-Multinomial distributed variables, enabling the derivation of posterior distributions for biomarker parameters under diverse model assumptions. Designed to be broadly applicable across various imaging modalities and biomarker types, the framework builds a foundation for generalizing reproducible and objective biomarker evaluation. To demonstrate utility, we apply the framework to whole-body diffusion-weighted MRI (WBDWI) to assess heterogeneous therapeutic responses in metastatic bone disease. Specifically, we analyze data from two patient studies investigating treatments for metastatic castrate-resistant prostate cancer (mCRPC). Our results reveal an approximately 70% response rate among individual tumors across both studies, objectively characterizing differential responses to systemic therapies and validating the clinical relevance of the proposed methodology. This Bayesian framework provides a powerful tool for advancing biomarker research across diverse imaging-based studies while offering valuable insights into specific clinical applications, such as mCRPC treatment response.

Signal-based AI-driven software solution for automated quantification of metastatic bone disease and treatment response assessment using Whole-Body Diffusion-Weighted MRI (WB-DWI) biomarkers in Advanced Prostate Cancer

We developed an AI-driven software solution to quantify metastatic bone disease from WB-DWI scans. Core technologies include: (i) a weakly-supervised Residual U-Net model generating a skeleton probability map to isolate bone; (ii) a statistical framework for WB-DWI intensity normalisation, obtaining a signal-normalised b=900s/mm^2 (b900) image; and (iii) a shallow convolutional neural network that processes outputs from (i) and (ii) to generate a mask of suspected bone lesions, characterised by higher b900 signal intensity due to restricted water diffusion. This mask is applied to the gADC map to extract TDV and gADC statistics. We tested the tool using expert-defined metastatic bone disease delineations on 66 datasets, assessed repeatability of imaging biomarkers (N=10), and compared software-based response assessment with a construct reference standard based on clinical, laboratory and imaging assessments (N=118). Dice score between manual and automated delineations was 0.6 for lesions within pelvis and spine, with an average surface distance of 2mm. Relative differences for log-transformed TDV (log-TDV) and median gADC were below 9% and 5%, respectively. Repeatability analysis showed coefficients of variation of 4.57% for log-TDV and 3.54% for median gADC, with intraclass correlation coefficients above 0.9. The software achieved 80.5% accuracy, 84.3% sensitivity, and 85.7% specificity in assessing response to treatment compared to the construct reference standard. Computation time generating a mask averaged 90 seconds per scan. Our software enables reproducible TDV and gADC quantification from WB-DWI scans for monitoring metastatic bone disease response, thus providing potentially useful measurements for clinical decision-making in APC patients.