Matthew Blackledge

Reza Kalantar, Sebastian Curcean, Jessica M Winfield et al.

T2-weighted magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) are essential components for cervical cancer diagnosis. However, combining these channels for training deep learning models are challenging due to misalignment of images. Here, we propose a novel multi-head framework that uses dilated convolutions and shared residual connections for separate encoding of multiparametric MRI images. We employ a residual U-Net model as a baseline, and perform a series of architectural experiments to evaluate the tumor segmentation performance based on multiparametric input channels and feature encoding configurations. All experiments were performed using a cohort including 207 patients with locally advanced cervical cancer. Our proposed multi-head model using separate dilated encoding for T2W MRI, and combined b1000 DWI and apparent diffusion coefficient (ADC) images achieved the best median Dice coefficient similarity (DSC) score, 0.823 (95% confidence interval (CI), 0.595-0.797), outperforming the conventional multi-channel model, DSC 0.788 (95% CI, 0.568-0.776), although the difference was not statistically significant (p>0.05). We investigated channel sensitivity using 3D GRAD-CAM and channel dropout, and highlighted the critical importance of T2W and ADC channels for accurate tumor segmentations. However, our results showed that b1000 DWI had a minor impact on overall segmentation performance. We demonstrated that the use of separate dilated feature extractors and independent contextual learning improved the model's ability to reduce the boundary effects and distortion of DWI, leading to improved segmentation performance. Our findings can have significant implications for the development of robust and generalizable models that can extend to other multi-modal segmentation applications.

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.

Konstantinos Zormpas-Petridis, Henrik Failmezger, Ioannis Roxanis et al.

The spectacular response observed in clinical trials of immunotherapy in patients with previously uncurable Melanoma, a highly aggressive form of skin cancer, calls for a better understanding of the cancer-immune interface. Computational pathology provides a unique opportunity to spatially dissect such interface on digitised pathological slides. Accurate cellular classification is a key to ensure meaningful results, but is often challenging even with state-of-art machine learning and deep learning methods. We propose a hierarchical framework, which mirrors the way pathologists perceive tumour architecture and define tumour heterogeneity to improve cell classification methods that rely solely on cell nuclei morphology. The SLIC superpixel algorithm was used to segment and classify tumour regions in low resolution H&E-stained histological images of melanoma skin cancer to provide a global context. Classification of superpixels into tumour, stroma, epidermis and lumen/white space, yielded a 97.7% training set accuracy and 95.7% testing set accuracy in 58 whole-tumour images of the TCGA melanoma dataset. The superpixel classification was projected down to high resolution images to enhance the performance of a single cell classifier, based on cell nuclear morphological features, and resulted in increasing its accuracy from 86.4% to 91.6%. Furthermore, a voting scheme was proposed to use global context as biological a priori knowledge, pushing the accuracy further to 92.8%. This study demonstrates how using the global spatial context can accurately characterise the tumour microenvironment and allow us to extend significantly beyond single-cell morphological classification.