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Data-driven Nucleus Subclassification on Colon H&E using Style-transferred Digital Pathology

Abstract

Understanding the way cells communicate, co-locate, and interrelate is essential to furthering our understanding of how the body functions. H&E is widely available, however, cell subtyping often requires expert knowledge and the use of specialized stains. To reduce the annotation burden, AI has been proposed for the classification of cells on H&E. For example, the recent Colon Nucleus Identification and Classification (CoNIC) Challenge focused on labeling 6 cell types on H&E of the colon. However, the CoNIC Challenge was unable to classify epithelial subtypes (progenitor, enteroendocrine, goblet), lymphocyte subtypes (B, helper T, cytotoxic T), and connective subtypes (fibroblasts). We use inter-modality learning to label previously un-labelable cell types on H&E. We take advantage of multiplexed immunofluorescence (MxIF) histology to label 14 cell subclasses. We performed style transfer on the same MxIF tissues to synthesize realistic virtual H&E which we paired with the MxIF-derived cell subclassification labels. We evaluated the efficacy of using a supervised learning scheme where the input was realistic-quality virtual H&E and the labels were MxIF-derived cell subclasses. We assessed our model on private virtual H&E and public real H&E. On virtual H&E, we were able to classify helper T cells and epithelial progenitors with positive predictive values of 0.34±0.150.34 \pm 0.15 (prevalence 0.03±0.010.03 \pm 0.01) and 0.47±0.10.47 \pm 0.1 (prevalence 0.07±0.020.07 \pm 0.02) respectively, when using ground truth centroid information. On real H&E we could classify helper T cells and epithelial progenitors with upper bound positive predictive values of 0.43±0.030.43 \pm 0.03 (parent class prevalence 0.21) and 0.94±0.020.94 \pm 0.02 (parent class prevalence 0.49) when using ground truth centroid information. This is the first work to provide cell type classification for helper T and epithelial progenitor nuclei on H&E.

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