Yu Zhao

Microsatellite instability (MSI) has been approved as a pan-cancer biomarker for immune checkpoint blockade (ICB) therapy. However, current MSI identification methods are not available for all patients. We proposed an ensemble multiple instance deep learning model to predict microsatellite status based on histopathology images, and interpreted the pathomics-based model with multi-omics correlation. Methods: Two cohorts of patients were collected, including 429 from The Cancer Genome Atlas (TCGA-COAD) and 785 from an Asian colorectal cancer (CRC) cohort (Asian-CRC). We established the pathomics model, named Ensembled Patch Likelihood Aggregation (EPLA), based on two consecutive stages: patch-level prediction and WSI-level prediction. The initial model was developed and validated in TCGA-COAD, and then generalized in Asian-CRC through transfer learning. The pathological signatures extracted from the model were analyzed with genomic and transcriptomic profiles for model interpretation.

Multiple instance learning (MIL) is a typical weakly-supervised learning method where the label is associated with a bag of instances instead of a single instance. Despite extensive research over past years, effectively deploying MIL remains an open and challenging problem, especially when the commonly assumed standard multiple instance (SMI) assumption is not satisfied. In this paper, we propose a multiple instance learning method based on deep graph convolutional network and feature selection (FS-GCN-MIL) for histopathological image classification. The proposed method consists of three components, including instance-level feature extraction, instance-level feature selection, and bag-level classification. We develop a self-supervised learning mechanism to train the feature extractor based on a combination model of variational autoencoder and generative adversarial network (VAE-GAN). Additionally, we propose a novel instance-level feature selection method to select the discriminative instance features. Furthermore, we employ a graph convolutional network (GCN) for learning the bag-level representation and then performing the classification. We apply the proposed method in the prediction of lymph node metastasis using histopathological images of colorectal cancer. Experimental results demonstrate that the proposed method achieves superior performance compared to the state-of-the-art methods.

Accurate and automatic organ segmentation is critical for computer-aided analysis towards clinical decision support and treatment planning. State-of-the-art approaches have achieved remarkable segmentation accuracy on large organs, such as the liver and kidneys. However, most of these methods do not perform well on small organs, such as the pancreas, gallbladder, and adrenal glands, especially when lacking sufficient training data. This paper presents an automatic approach for small organ segmentation with limited training data using two cascaded steps-localization and segmentation. The localization stage involves the extraction of the region of interest after the registration of images to a common template and during the segmentation stage, a voxel-wise label map of the extracted region of interest is obtained and then transformed back to the original space. In the localization step, we propose to utilize a graph-based groupwise image registration method to build the template for registration so as to minimize the potential bias and avoid getting a fuzzy template. More importantly, a novel knowledge-aided convolutional neural network is proposed to improve segmentation accuracy in the second stage. This proposed network is flexible and can combine the effort of both deep learning and traditional methods, consequently achieving better segmentation relative to either of individual methods. The ISBI 2015 VISCERAL challenge dataset is used to evaluate the presented approach. Experimental results demonstrate that the proposed method outperforms cutting-edge deep learning approaches, traditional forest-based approaches, and multi-atlas approaches in the segmentation of small organs.