Interpretable Segmentation of Amyloid-βStained Whole Slide Images of Brain Tissue

Neurodegenerative disease pathologies have been reported in both grey matter (GM) and white matter (WM) with different density distributions, an automated separation of GM/WM would be extremely advantageous for aiding in neuropathologic deep phenotyping. Standard segmentation methods typically involve manual annotations, where a trained researcher traces the delineation of GM/WM in ultra-high-resolution Whole Slide Images (WSIs). This method can be time-consuming and subjective, preventing the analysis of large amounts of WSIs at scale. This paper proposes an automated segmentation pipeline combining a Convolutional Neural Network (CNN) module for segmenting GM/WM regions and a post-processing module to remove artifacts/residues of tissues as well as generate XML annotations that can be visualized via Aperio ImageScope. First, we investigate two baseline models for medical image segmentation: FCN, and U-Net. Then we propose a patch-based approach, ResNet-Patch, to classify the GM/WM/background regions. In addition, we integrate a Neural Conditional Random Field (NCRF) module, ResNet-NCRF, to model and incorporate the spatial correlations among neighboring patches. Although their mechanisms are greatly different, both U-Net and ResNet-Patch/ResNet-NCRF achieve Intersection over Union (IoU) of more than 90% in GM and more than 80% in WM, while ResNet-Patch achieves 1% superior to U-Net with lower variance among various WSIs. ResNet-NCRF further improves the IoU by 3% for WM compared to ResNet-Patch before post-processing. We also apply gradient-weighted class activation mapping (Grad-CAM) to interpret the segmentation masks and provide relevant explanations and insights.