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Predicting Crohn’s disease severity in the colon using mixed cell nucleus density from pseudo labels

Posted by on Thursday, December 1, 2022 in Big Data, Crohn's disease, Deep Learning.

Lucas W. Remedios, Shunxing Bao, Cailey I. Kerley, Leon Y. Cai, François Rheault, Ruining Deng, Can Cui, Sophie Chiron, Ken S. Lau, Joseph T. Roland, Mary K. Washington, Lori A. Coburn, Keith T. Wilson, Yuankai Huo, Bennett A. Landman (2023). Predicting Crohn’s disease severity in the colon using mixed cell nucleus density from pseudo labels. SPIE Medical Imaging : Digital and Computational Pathology 2023.

Full text: NIHMSID

Abstract

Crohn’s disease (CD) is a debilitating inflammatory bowel disease with no known cure. Computational analysis of hematoxylin and eosin (H&E) stained colon biopsy whole slide images (WSIs) from CD patients provides the opportunity to discover unknown and complex relationships between tissue cellular features and disease severity. While there have been works using cell nuclei-derived features for predicting slide-level traits, this has not been performed on CD H&E WSIs for classifying normal tissue from CD patients vs active CD and assessing slide label-predictive performance while using both separate and combined information from pseudo-segmentation labels of nuclei from neutrophils, eosinophils, epithelial cells, lymphocytes, plasma cells, and connective cells. We used 413 WSIs of CD patient biopsies and calculated normalized histograms of nucleus density for the six cell classes for each WSI. We used a support vector machine to classify the truncated singular value decomposition representations of the normalized histograms as normal or active CD with four-fold cross-validation in rounds where nucleus types were first compared individually, the best was selected, and further types were added each round. We found that neutrophils were the most predictive individual nucleus type, with an AUC of 0.92 ± 0.0003 on the withheld test set. Adding information improved cross-validation performance for the first two rounds and on the withheld test set for the first three rounds, though performance metrics did not increase substantially beyond when neutrophils were used alone.

UMAP of the normalized histogram representation of WSI neutrophil density for the entire dataset. All patches in this figure depict the 256 × 256 pixel CLAM patch with the maximum neutrophil density from the corresponding WSI. The UMAP displayed with patches depicts more clearly visible crypts and tissue edges in the normal cluster max patches than the active disease cluster (A). The UMAP displayed with circle markers highlights the separability of the two classes (B). Example patches are shown with their predicted neutrophil segmentation in green (C, D, E, F). Looking deep into the normal cluster, expected patches (C) and active disease outliers (D) show tissue edges and few segmented neutrophils. In the active disease cluster, expected patches (E) and normal tissue CD outliers (F) both show a larger number of segmented neutrophils, with fewer tissue edges visible (F).
UMAP of the normalized histogram representation of WSI neutrophil density for the entire dataset. All patches in this figure depict the 256 × 256 pixel CLAM patch with the maximum neutrophil density from the corresponding WSI. The UMAP displayed with patches depicts more clearly visible crypts and tissue edges in the normal cluster max patches than the active disease cluster (A). The UMAP displayed with circle markers highlights the separability of the two classes (B). Example patches are shown with their predicted neutrophil segmentation in green (C, D, E, F). Looking deep into the normal cluster, expected patches (C) and active disease outliers (D) show tissue edges and few segmented neutrophils. In the active disease cluster, expected patches (E) and normal tissue CD outliers (F) both show a larger number of segmented neutrophils, with fewer tissue edges visible (F).