Semantic segmentation of various tissue and nuclei types in histology images is fundamental to many downstream tasks in the area of computational pathology (CPath). In recent years, Deep Learning (DL) methods have been shown to perform well on segmentation tasks but DL methods generally require a large amount of pixel-wise annotated data. Pixel-wise annotation sometimes requires expert's knowledge and time which is laborious and costly to obtain. In this paper, we present a consistency based semi-supervised learning (SSL) approach that can help mitigate this challenge by exploiting a large amount of unlabelled data for model training thus alleviating the need for a large annotated dataset. However, SSL models might also be susceptible to changing context and features perturbations exhibiting poor generalisation due to the limited training data. We propose an SSL method that learns robust features from both labelled and unlabelled images by enforcing consistency against varying contexts and feature perturbations. The proposed method incorporates context-aware consistency by contrasting pairs of overlapping images in a pixel-wise manner from changing contexts resulting in robust and context invariant features. We show that cross-consistency training makes the encoder features invariant to different perturbations and improves the prediction confidence. Finally, entropy minimisation is employed to further boost the confidence of the final prediction maps from unlabelled data. We conduct an extensive set of experiments on two publicly available large datasets (BCSS and MoNuSeg) and show superior performance compared to the state-of-the-art methods.

Automatic tissue classification is a fundamental task in computational pathology for profiling tumor micro-environments. Deep learning has advanced tissue classification performance at the cost of significant computational power. Shallow networks have also been end-to-end trained using direct supervision however their performance degrades because of the lack of capturing robust tissue heterogeneity. Knowledge distillation has recently been employed to improve the performance of the shallow networks used as student networks by using additional supervision from deep neural networks used as teacher networks. In the current work, we propose a novel knowledge distillation algorithm to improve the performance of shallow networks for tissue phenotyping in histology images. For this purpose, we propose multi-layer feature distillation such that a single layer in the student network gets supervision from multiple teacher layers. In the proposed algorithm, the size of the feature map of two layers is matched by using a learnable multi-layer perceptron. The distance between the feature maps of the two layers is then minimized during the training of the student network. The overall objective function is computed by summation of the loss over multiple layers combination weighted with a learnable attention-based parameter. The proposed algorithm is named as Knowledge Distillation for Tissue Phenotyping (KDTP). Experiments are performed on five different publicly available histology image classification datasets using several teacher-student network combinations within the KDTP algorithm. Our results demonstrate a significant performance increase in the student networks by using the proposed KDTP algorithm compared to direct supervision-based training methods.

Estimating over-amplification of human epidermal growth factor receptor 2 (HER2) on invasive breast cancer is regarded as a significant predictive and prognostic marker. We propose a novel deep reinforcement learning (DRL)-based model that treats immunohistochemical (IHC) scoring of HER2 as a sequential learning task. For a given image tile sampled from multi-resolution giga-pixel whole slide image (WSI), the model learns to sequentially identify some of the diagnostically relevant regions of interest (ROIs) by following a parameterized policy. The selected ROIs are processed by recurrent and residual convolution networks to learn the discriminative features for different HER2 scores and predict the next location, without requiring to process all the sub-image patches of a given tile for predicting the HER2 score, mimicking the histopathologist who would not usually analyze every part of the slide at the highest magnification. The proposed model incorporates a task-specific regularization term and inhibition of return mechanism to prevent the model from revisiting the previously attended locations. We evaluated our model on two IHC datasets: a publicly available dataset from the HER2 scoring challenge contest and another dataset consisting of WSIs of gastroenteropancreatic neuroendocrine tumor sections stained with Glo1 marker. We demonstrate that the proposed model outperforms other methods based on state-of-the-art deep convolutional networks. To the best of our knowledge, this is the first study using DRL for IHC scoring and could potentially lead to wider use of DRL in the domain of computational pathology reducing the computational burden of the analysis of large multi-gigapixel histology images.