Nucleus subtype classification using inter-modality learning

Lucas W. Remedios, Shunxing Bao, Samuel W. Remedios, Ho Hin Lee, Leon Cai, Thomas Li, Ruining Deng, Can Cui, Jia Li, Qi Liu, Ken S. Lau, Joseph T. Roland, Mary K. Washington, Lori A. Coburn, Keith T. Wilson, Yuankai Huo, and Bennett A. Landman. “Nucleus Subtype Classification Using Inter-modality Learning.” Proceedings of SPIE Medical Imaging 2024: Digital and Computational Pathology, vol. 12933, 129330F, 2024, San Diego, California,

Understanding how cells communicate, co-locate, and interrelate is essential for grasping human physiology. Hematoxylin and eosin (H&E) staining is widely used in clinical studies and research. The Colon Nucleus Identification and Classification (CoNIC) Challenge recently advanced artificial intelligence to label six cell types on H&E stained colon tissues. However, this only covers a small fraction of potential cell classifications, missing various epithelial (progenitor, endocrine, goblet), lymphocyte (B cells, helper T cells, cytotoxic T cells), and connective tissue (fibroblasts, stromal) subtypes.

To address this limitation, the study proposes using inter-modality learning to label previously unclassifiable cell types on virtual H&E images. The researchers utilized multiplexed immunofluorescence (MxIF) histology imaging to identify 14 cell type subclasses. By performing style transfer, they synthesized virtual H&E images from MxIF and transferred the detailed labels from MxIF to these virtual H&E images. They then assessed the effectiveness of this learning approach.

The results demonstrated that helper T cells and progenitor cells could be identified 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 images. This method represents a promising step toward automating cell type annotation in digital pathology, significantly enhancing the capability to classify diverse cell types beyond current limitations.

Figure 1. We leveraged inter-modality learning to investigate identification of cells on virtual H&E staining that are traditionally viewed with specialized staining. The realistic quality of our virtual H&E holds at multiple scales (top row). Representative nuclei from each of our 14 classes in both virtual H&E and MxIF illustrate intensity and morphological variation across cell types (lower section). Green is used to denote the MxIF stain of interest, which is a different stain for each of the 14 cell types in this figure. While the signal to identify these classes of nuclei is present in MxIF, the nucleus classes are more difficult to distinguish on virtual H&E.