A Novel Generative Artificial Intelligence Method for Interference Study on Multiplex Brightfield Immunohistochemistry Images

Multiplex brightfield imaging offers the advantage of simultaneously analyzing multiple biomarkers on a single slide, as opposed to single biomarker labeling on multiple consecutive slides. To accurately analyze multiple biomarkers localized at the same cellular compartment, two representative biomarker sets were selected as assay models - cMET-PDL1-EGFR and CD8-LAG3-PDL1, where all three biomarkers can co-localize on the cell membrane. One of the most crucial preliminary stages for analyzing such assay is identifying each unique chromogen on individual cells. This is a challenging problem due to the co-localization of membrane stains from all the three biomarkers. It requires advanced color unmixing for creating the equivalent singleplex images from each triplex image for each biomarker. In this project, we developed a cycle-Generative Adversarial Network (cycle-GAN) method for unmixing the triplex images generated from the above-mentioned assays. Three different models were designed to generate the singleplex image for each of the three stains Tamra (purple), QM-Dabsyl (yellow) and Green. A notable novelty of our approach was that the input to the network were images in the optical density domain instead of conventionally used RGB images. The use of the optical density domain helped in reducing the blurriness of the synthetic singleplex images, which was often observed when the network was trained on RGB images. The cycle-GAN models were validated on 10,800 lung, gastric and colon images for the cMET-PDL1-EGFR assay and 3600 colon images for the CD8-LAG3-PDL1 assay. Visual as well as quantified assessments demonstrated that the proposed method is effective and efficient when compared with the manual reviewing results and is readily applicable to various multiplex assays.

Continual Learning for Tumor Classification in Histopathology Images

Recent years have seen great advancements in the development of deep learning models for histopathology image analysis in digital pathology applications, evidenced by the increasingly common deployment of these models in both research and clinical settings. Although such models have shown unprecedented performance in solving fundamental computational tasks in DP applications, they suffer from catastrophic forgetting when adapted to unseen data with transfer learning. With an increasing need for deep learning models to handle ever changing data distributions, including evolving patient population and new diagnosis assays, continual learning models that alleviate model forgetting need to be introduced in DP based analysis. However, to our best knowledge, there is no systematic study of such models for DP-specific applications. Here, we propose CL scenarios in DP settings, where histopathology image data from different sources/distributions arrive sequentially, the knowledge of which is integrated into a single model without training all the data from scratch. We then established an augmented dataset for colorectal cancer H&E classification to simulate shifts of image appearance and evaluated CL model performance in the proposed CL scenarios. We leveraged a breast tumor H&E dataset along with the colorectal cancer to evaluate CL from different tumor types. In addition, we evaluated CL methods in an online few-shot setting under the constraints of annotation and computational resources. We revealed promising results of CL in DP applications, potentially paving the way for application of these methods in clinical practice.