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.

Cross-modality Attention-based Multimodal Fusion for Non-small Cell Lung Cancer (NSCLC) Patient Survival Prediction

Cancer prognosis and survival outcome predictions are crucial for therapeutic response estimation and for stratifying patients into various treatment groups. Medical domains concerned with cancer prognosis are abundant with multiple modalities, including pathological image data and non-image data such as genomic information. To date, multimodal learning has shown potential to enhance clinical prediction model performance by extracting and aggregating information from different modalities of the same subject. This approach could outperform single modality learning, thus improving computer-aided diagnosis and prognosis in numerous medical applications. In this work, we propose a cross-modality attention-based multimodal fusion pipeline designed to integrate modality-specific knowledge for patient survival prediction in non-small cell lung cancer (NSCLC). Instead of merely concatenating or summing up the features from different modalities, our method gauges the importance of each modality for feature fusion with cross-modality relationship when infusing the multimodal features. Compared with single modality, which achieved c-index of 0.5772 and 0.5885 using solely tissue image data or RNA-seq data, respectively, the proposed fusion approach achieved c-index 0.6587 in our experiment, showcasing the capability of assimilating modality-specific knowledge from varied modalities.

Weakly Supervised Multi-Task Learning for Cell Detection and Segmentation

Cell detection and segmentation is fundamental for all downstream analysis of digital pathology images. However, obtaining the pixel-level ground truth for single cell segmentation is extremely labor intensive. To overcome this challenge, we developed an end-to-end deep learning algorithm to perform both single cell detection and segmentation using only point labels. This is achieved through the combination of different task orientated point label encoding methods and a multi-task scheduler for training. We apply and validate our algorithm on PMS2 stained colon rectal cancer and tonsil tissue images. Compared to the state-of-the-art, our algorithm shows significant improvement in cell detection and segmentation without increasing the annotation efforts.