Abstract 6185: Generative AI for virtual HE-staining of whole slide images of unstained breast cancer tissue

Abstract Introduction Hematoxylin and eosin (HE) is the standard stain used in histology to make tissue visible to the human eye by highlighting certain cellular and tissue structures, and it is a technique that is widely used in the diagnosis of cancer and other pathologies. Chemical staining, however, is irreversible, making the tissue unusable for subsequent measurements, such as spatial transcriptomics. Here we utilize generative AI method based on pix2pix image-to-image translation to generate virtual HE-staining for whole slide images (WSIs) acquired of unstained tissue with brightfield microscopy and perform a thorough histological evaluation for the feasibility in breast cancer diagnostics. Materials and Methods We optimized sample preparation and imaging setup for virtual staining purposes, and developed a custom generative adversarial network architecture for learning the virtual staining from paires samples of unstained and H&E stained tissue. Here, we focus on the utility of virtual staining in breast cancer diagnostics, using a set of breast cancer samples for acquiring whole slide images from unstained tissue before H&E staining and from reference H&E stained tissue after chemical staining. Hold-out set of sample pairs are left for validation, allowing us to evaluate the virtual staining performance for a vast array of tissue components and to examine the potential shortcomings in staining reproduction. We use a comprehensive set of quantitative metrics both on pixel and object level to evaluate virtual staining quality. In addition, we perform thorough visual evaluation of histological feasibility by histology experts to examine the computational staining. Results We demonstrate that by careful optimization of both sample preparation and imaging workflow, as well as the computational methods, generative adversarial networks can be used for virtual staining of whole slide images of breast cancer tissue acquired from unstained tissue using regular bright field microscopy. We analyzed the virtual staining performance quantitatively and visually, and highlight the potential of the method through successful cases and demonstrate the applicability in breast cancer diagnostics, as well as discuss the challenges and shortcomings of virtual staining for clinical samples. Conclusions We demonstrate the potential of virtual HE staining for clinical histopathology of breast cancer tissue. Notably, our virtual staining based on generative AI shows promise towards more sustainable and streamlined sample processing and staining process in digital pathology. Citation Format: Leena Latonen, Umair Khan, Sonja Koivukoski, Johan Hartman, Pekka Ruusuvuori. Generative AI for virtual HE-staining of whole slide images of unstained breast cancer tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6185.