Dual-modality imaging of immunofluorescence and imaging mass cytometry for high-resolution whole slide imaging with accurate single-cell segmentation
- 1. Department of Biomedical Engineering and Computational Biology Program, Oregon Health and Science University
- 2. Early Cancer Institute, University of Cambridge, Cambridge, UK
- 3. Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK
- 4. Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR, USA
- 5. Department of Biomedical Engineering and Computational Biology Program, Oregon Health and Science University, Portland, OR, USA
Description
Imaging mass cytometry (IMC) is a powerful multiplexed tissue imaging technology that allows simultaneous detection of more than 30 makers on a single slide. It has been increasingly used for single-cell based spatial phenotyping in a wide range of samples. However, it only acquires a small, rectangle field of view (FOV) with a low image resolution that hinders downstream analysis. Here, we reported a highly practical dual-modality imaging method that combines high-resolution immunofluorescence (IF) and high-dementional IMC on the same tissue slide. Our computational pipeline uses the whole slide image (WSI) of IF as spatial reference, integrates small FOV IMC into a WSI of IMC. The high-resolution IF images enable accurate single-cell segmentation to extract robust high-dimensional IMC features for downstream analysis. We applied this method in esophageal adenocarcinoma of different stages, identified the single-cell pathology landscape via reconstruction of WSI IMC images and demonstrated the advantage of the dual-modality imaging strategy.