Antonio Candito

Objective . 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. Approach . 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 = 900 s 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 , defined as multidisciplinary consensus based on ⩾12 months of imaging, clinical, and laboratory follow-up ( N = 118). Main results . Average dice score between manual and automated delineations was 0.6 for lesions within pelvis and spine, with an average surface distance of 2 mm. 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 90 s per scan. Significance . 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.

(1) Background: We assessed the test–re-test repeatability of radiomics in metastatic castration-resistant prostate cancer (mCPRC) bone disease on whole-body diffusion-weighted (DWI) and T1-weighted Dixon MRI. (2) Methods: In 10 mCRPC patients, 1.5 T MRI, including DWI and T1-weighted gradient-echo Dixon sequences, was performed twice on the same day. Apparent diffusion coefficient (ADC) and relative fat-fraction-percentage (rFF%) maps were calculated. Per study, up to 10 target bone metastases were manually delineated on DWI and Dixon images. All 106 radiomic features included in the Pyradiomics toolbox were derived for each target volume from the ADC and rFF% maps. To account for inter- and intra-patient measurement repeatability, the log-transformed individual target measurements were fitted to a hierarchical model, represented as a Bayesian network. Repeatability measurements, including the intraclass correlation coefficient (ICC), were derived. Feature ICCs were compared with mean ADC and rFF ICCs. (3) Results: A total of 65 DWI and 47 rFF% targets were analysed. There was no significant bias for any features. Pairwise correlation revealed fifteen ADC and fourteen rFF% feature sub-groups, without specific patterns between feature classes. The median intra-patient ICC was generally higher than the inter-patient ICC. Features that describe extremes in voxel values (minimum, maximum, range, skewness, and kurtosis) showed generally lower ICCs. Several mostly shape-based texture features were identified, which showed high inter- and intra-patient ICCs when compared with the mean ADC or mean rFF%, respectively. (4) Conclusions: Pyradiomics texture features of mCRPC bone metastases varied greatly in inter- and intra-patient repeatability. Several features demonstrated good repeatability, allowing for further exploration as diagnostic parameters in mCRPC bone disease.

Background: Whole-Body Diffusion-Weighted Imaging (WBDWI) is an established technique for staging and evaluating treatment response in patients with multiple myeloma (MM) and advanced prostate cancer (APC). However, WBDWI scans show inter- and intra-patient intensity signal variability. This variability poses challenges in accurately quantifying bone disease, tracking changes over follow-up scans, and developing automated tools for bone lesion delineation. Here, we propose a novel automated pipeline for inter-station, inter-scan image signal standardisation on WBDWI that utilizes robust segmentation of the spinal canal through deep learning. Methods: We trained and validated a supervised 2D U-Net model to automatically delineate the spinal canal (both the spinal cord and surrounding cerebrospinal fluid, CSF) in an initial cohort of 40 patients who underwent WBDWI for treatment response evaluation (80 scans in total). Expert-validated contours were used as the target standard. The algorithm was further semi-quantitatively validated on four additional datasets (three internal, one external, 207 scans total) by comparing the distributions of average apparent diffusion coefficient (ADC) and volume of the spinal cord derived from a two-component Gaussian mixture model of segmented regions. Our pipeline subsequently standardises WBDWI signal intensity through two stages: (i) normalisation of signal between imaging stations within each patient through histogram equalisation of slices acquired on either side of the station gap, and (ii) inter-scan normalisation through histogram equalisation of the signal derived within segmented spinal canal regions. This approach was semi-quantitatively validated in all scans available to the study (N = 287). Results: The test dice score, precision, and recall of the spinal canal segmentation model were all above 0.87 when compared to manual delineation. The average ADC for the spinal cord (1.7 × 10⁻³ mm²/s) showed no significant difference from the manual contours. Furthermore, no significant differences were found between the average ADC values of the spinal cord across the additional four datasets. The signal-normalised, high-b-value images were visualised using a fixed contrast window level and demonstrated qualitatively better signal homogeneity across scans than scans that were not signal-normalised. Conclusion: Our proposed intensity signal WBDWI normalisation pipeline successfully harmonises intensity values across multi-centre cohorts. The computational time required is less than 10 s, preserving contrast-to-noise and signal-to-noise ratios in axial diffusion-weighted images. Importantly, no changes to the clinical MRI protocol are expected, and there is no need for additional reference MRI data or follow-up scans.

Objectives: To assess the repeatability of quantitative multiparametric whole-body MRI (mpWB-MRI) parameters in advanced prostate cancer (APC) bone metastases. Methods: 1.5T MRI was performed twice on the same day in 10 APC patients. MpWB-MRI-included diffusion weighted imaging (DWI) and T₁-weighted gradient-echo 2-point Dixon sequences. ADC and relative fat-fraction percentage (rFF%) maps were calculated, respectively. A radiologist delineated up to 10 target bone metastases per study. Means of ADC, b900 signal intensity(SI), normalised b900 SI, rFF% and maximum diameter (MD) for each target lesion and overall parameter averages across all targets per patient were recorded. The total disease volume (tDV in ml) was manually delineated on b900 images and mean global (g)ADC was derived. Bland-Altman analyses were performed with calculation of 95% repeatability coefficients (RC). Results: Seventy-three individual targets (median MD 26 mm) were included. Lesion mean ADC RC was 12.5%, mean b900 SI RC 137%, normalised mean b900 SI RC 110%, rFF% RC 3.2 and target MD RC 5.5 mm (16.3%). Patient target lesion average mean ADC RC was 6.4%, b900 SI RC 104% and normalised mean b900 SI RC 39.6%. Target average rFF% RC was 1.8, average MD RC 1.3 mm (4.8%). tDV segmentation RC was 6.4% and mean gADC RC 5.3%. Conclusions: APC bone metastases’ ADC, rFF% and maximum diameter, tDV and gADC show good repeatability. Advances in knowledge: APC bone metastases’ mean ADC and rFF% measurements of single lesions and global disease volumes are repeatable, supporting their potential role as quantitative biomarkers in metastatic bone disease.