Multiresolution semantic segmentation of biological structures in digital histopathology.

Purpose: Semantic segmentation in high-resolution, histopathology whole slide images (WSIs) is an important fundamental task in various pathology applications. Convolutional neural networks (CNN) are the state-of-the-art approach for image segmentation. A patch-based CNN approach is often employed because of the large size of WSIs; however, segmentation performance is sensitive to the field-of-view and resolution of the input patches, and balancing the trade-offs is challenging when there are drastic size variations in the segmented structures. We propose a multiresolution semantic segmentation approach, which is capable of addressing the threefold trade-off between field-of-view, computational efficiency, and spatial resolution in histopathology WSIs. Approach: We propose a two-stage multiresolution approach for semantic segmentation of histopathology WSIs of mouse lung tissue and human placenta. In the first stage, we use four different CNNs to extract the contextual information from input patches at four different resolutions. In the second stage, we use another CNN to aggregate the extracted information in the first stage and generate the final segmentation masks. Results: The proposed method reported 95.6%, 92.5%, and 97.1% in our single-class placenta dataset and 97.1%, 87.3%, and 83.3% in our multiclass lung dataset for pixel-wise accuracy, mean Dice similarity coefficient, and mean positive predictive value, respectively. Conclusions: The proposed multiresolution approach demonstrated high accuracy and consistency in the semantic segmentation of biological structures of different sizes in our single-class placenta and multiclass lung histopathology WSI datasets. Our study can potentially be used in automated analysis of biological structures, facilitating the clinical research in histopathology applications.

Automated detection of microscopic placental features indicative of maternal vascular malperfusion using machine learning.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) and fetal growth restriction (FGR) are common obstetrical complications, often with pathological features of maternal vascular malperfusion (MVM) in the placenta. Currently, clinical placental pathology methods involve a manual visual examination of histology sections, a practice that can be resource-intensive and demonstrates moderate-to-poor inter-pathologist agreement on diagnostic outcomes, dependant on the degree of pathologist sub-specialty training. METHODS: This study aims to apply machine learning (ML) feature extraction methods to classify digital images of placental histopathology specimens, collected from cases of HDP [pregnancy induced hypertension (PIH), preeclampsia (PE), PE + FGR], normotensive FGR, and healthy pregnancies, according to the presence or absence of MVM lesions. 159 digital images were captured from histological placental specimens, manually scored for MVM lesions (MVM- or MVM+) and used to develop a support vector machine (SVM) classifier model, using features extracted from pre-trained ResNet18. The model was trained with data augmentation and shuffling, with the performance assessed for patch-level and image-level classification through measurements of accuracy, precision, and recall using confusion matrices. RESULTS: The SVM model demonstrated accuracies of 70 % and 79 % for patch-level and image-level MVM classification, respectively, with poorest performance observed on images with borderline MVM presence, as determined through post hoc observation. DISCUSSION: The results are promising for the integration of ML methods into the placental histopathological examination process. Using this study as a proof-of-concept will lead our group and others to carry ML models further in placental histopathology.

Fully automated estimation of the mean linear intercept in histopathology images of mouse lung tissue.

Purpose: The mean linear intercept (MLI) score is a common metric for quantification of injury in lung histopathology images. The automated estimation of the MLI score is a challenging task because it requires accurate segmentation of different biological components of the lung tissue. Therefore, the most widely used approaches for MLI quantification are based on manual/semi-automated assessment of lung histopathology images, which can be expensive and time-consuming. We describe a fully automated pipeline for MLI estimation, which is capable of producing results comparable to human raters. Approach: We use a convolutional neural network based on U-Net architecture to segment the diagnostically relevant tissue segments in the whole slide images (WSI) of the mouse lung tissue. The proposed method extracts multiple field-of-view (FOV) images from the tissue segments and screen the FOV images, rejecting images based on presence of certain biological structures (i.e., blood vessels and bronchi). We used color slicing and region growing for segmentation of different biological structures in each FOV image. Results: The proposed method was tested on ten WSIs from mice and compared against the scores provided by three human raters. In segmenting the relevant tissue segments, our method obtained a mean accuracy, Dice coefficient, and Hausdorff distance of 98.34%, 98.22%, and 109.68 µ m , respectively. Our proposed method yields a mean precision, recall, and F 1 -score of 93.37%, 83.47%, and 87.87%, respectively, in screening of FOV images. There was substantial agreement found between the proposed method and the manual scores (Fleiss Kappa score of 0.76). The mean difference between the calculated MLI score between the automated method and average rater's score was 2.33 ± 4.13 ( 4.25 % ± 5.67 % ). Conclusion: The proposed pipeline for automated calculation of the MLI score demonstrates high consistency and accuracy with human raters and can be a potential replacement for manual/semi-automated approaches in the field.