Ricardo Donners

A. Candito, A. Dragan, R. Holbrey et al.

Background: Apparent Diffusion Coefficient (ADC) values and Total Diffusion Volume (TDV) from Whole-body diffusion-weighted MRI (WB-DWI) are recognized cancer imaging biomarkers. However, manual disease delineation for ADC and TDV measurements is unfeasible in clinical practice, demanding automation. As a first step, we propose an algorithm to generate fast and reproducible probability maps of the skeleton, adjacent internal organs (liver, spleen, urinary bladder, and kidneys), and spinal canal. Methods: We developed an automated deep-learning pipeline based on a 3D patch-based Residual U-Net architecture that localises and delineates these anatomical structures on WB-DWI. The algorithm was trained using "soft labels" (non-binary segmentations) derived from a computationally intensive atlas-based approach. For training and validation, we employed a multi-centre WB-DWI dataset comprising 532 scans from patients with Advanced Prostate Cancer (APC) or Multiple Myeloma (MM), with testing on 45 patients. Results: Our weakly-supervised deep learning model achieved an average dice score of 0.67 for whole skeletal delineation, 0.76 when excluding ribcage, 0.83 for internal organs, and 0.86 for spinal canal, with average surface distances below 3mm. Relative median ADC differences between automated and manual full-body delineations were below 10%. The model was 12x faster than the atlas-based registration algorithm (25 sec vs. 5 min). Two experienced radiologists rated the model's outputs as either "good" or "excellent" on test scans, with inter-reader agreement from fair to substantial (Gwet's AC1 = 0.27-0.72). Conclusion: The model offers fast, reproducible probability maps for localising and delineating body regions on WB-DWI, potentially enabling non-invasive imaging biomarker quantification to support disease staging and treatment response assessment.

Antonio Candito, Matthew D Blackledge, Richard Holbrey et al.

Quantitative assessment of treatment response in Advanced Prostate Cancer (APC) with bone metastases remains an unmet clinical need. Whole-Body Diffusion-Weighted MRI (WB-DWI) provides two response biomarkers: Total Diffusion Volume (TDV) and global Apparent Diffusion Coefficient (gADC). However, tracking post-treatment changes of TDV and gADC from manually delineated lesions is cumbersome and increases inter-reader variability. We developed a software to automate this process. 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 (N=118). Average 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 8.8% and 5%, respectively. Repeatability analysis showed coefficients of variation of 4.6% for log-TDV and 3.5% for median gADC, with intraclass correlation coefficients of 0.94 or higher. The software achieved 80.5% accuracy, 84.3% sensitivity, and 85.7% specificity in assessing response to treatment. Average computation time was 90s per scan.