PurposeCells are building blocks for human physiology; consequently, understanding the way cells communicate, co-locate, and interrelate is essential to furthering our understanding of how the body functions in both health and disease. Hematoxylin and eosin (H&E) is the standard stain used in histological analysis of tissues in both clinical and research settings. Although H&E is ubiquitous and reveals tissue microanatomy, the classification and mapping of cell subtypes often require the use of specialized stains. The recent CoNIC Challenge focused on artificial intelligence classification of six types of cells on colon H&E but was unable to classify epithelial subtypes (progenitor, enteroendocrine, goblet), lymphocyte subtypes (B, helper T, cytotoxic T), and connective subtypes (fibroblasts). We propose to use inter-modality learning to label previously un-labelable cell types on H&E.ApproachWe took advantage of the cell classification information inherent in multiplexed immunofluorescence (MxIF) histology to create cell-level annotations for 14 subclasses. Then, we performed style transfer on the MxIF to synthesize realistic virtual H&E. We assessed the efficacy of a supervised learning scheme using the virtual H&E and 14 subclass labels. We evaluated our model on virtual H&E and real H&E.ResultsOn virtual H&E, we were able to classify helper T cells and epithelial progenitors with positive predictive values of 0.34±0.15 (prevalence 0.03±0.01) and 0.47±0.1 (prevalence 0.07±0.02), respectively, when using ground truth centroid information. On real H&E, we needed to compute bounded metrics instead of direct metrics because our fine-grained virtual H&E predicted classes had to be matched to the closest available parent classes in the coarser labels from the real H&E dataset. For the real H&E, we could classify bounded metrics for the helper T cells and epithelial progenitors with upper bound positive predictive values of 0.43±0.03 (parent class prevalence 0.21) and 0.94±0.02 (parent class prevalence 0.49) when using ground truth centroid information.ConclusionsThis is the first work to provide cell type classification for helper T and epithelial progenitor nuclei on H&E.
Understanding the way cells communicate, co-locate, and interrelate is essential to understanding human physiology. Hematoxylin and eosin (H&E) staining is ubiquitously available both for clinical studies and research. The Colon Nucleus Identification and Classification (CoNIC) Challenge has recently innovated on robust artificial intelligence labeling of six cell types on H&E stains of the colon. However, this is a very small fraction of the number of potential cell classification types. Specifically, the CoNIC Challenge is unable to classify epithelial subtypes (progenitor, endocrine, goblet), lymphocyte subtypes (B, helper T, cytotoxic T), or connective subtypes (fibroblasts, stromal). In this paper, we propose to use inter-modality learning to label previously un-labelable cell types on virtual H&E. We leveraged multiplexed immunofluorescence (MxIF) histology imaging to identify 14 subclasses of cell types. We performed style transfer to synthesize virtual H&E from MxIF and transferred the higher density labels from MxIF to these virtual H&E images. We then evaluated the efficacy of learning in this approach. We identified helper T and progenitor nuclei with positive predictive values of 0.34 ± 0.15 (prevalence 0.03 ± 0.01) and 0.47 ± 0.1 (prevalence 0.07 ± 0.02) respectively on virtual H&E. This approach represents a promising step towards automating annotation in digital pathology.
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.
The Gut Cell Atlas (GCA), an initiative funded by the Helmsley Charitable Trust, seeks to create a reference platform to understand the human gut, with a specific focus on Crohn’s disease. Although a primary focus of the GCA is on focusing on single-cell profiling, we seek to provide a framework to integrate other analyses on multimodality data such as electronic health record data, radiological images, and histology tissues/images. Herein, we use the research electronic data capture (REDCap) system as the central tool for a secure web application that supports protected health information (PHI) restricted access. Our innovations focus on addressing the challenges with tracking all specimens and biopsies, validating manual data entry at scale, and sharing organizational data across the group. We present a scalable, cross-platform barcode printing/record system that integrates with REDCap. The central informatics infrastructure to support our design is a tuple table to track longitudinal data entry and sample tracking. The current data collection (by December 2020) is illustrated with types and formats of the data that the system collects. We estimate that one terabyte is needed for data storage per patient study. Our proposed data sharing informatics system addresses the challenges with integrating physical sample tracking, large files, and manual data entry with REDCap.
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