LYSTO: The Lymphocyte Assessment Hackathon and Benchmark Dataset

We introduce LYSTO, the Lymphocyte Assessment Hackathon, which was held in conjunction with the MICCAI 2019 Conference in Shenzen (China). The competition required participants to automatically assess the number of lymphocytes, in particular T-cells, in histopathological images of colon, breast, and prostate cancer stained with CD3 and CD8 immunohistochemistry. Differently from other challenges setup in medical image analysis, LYSTO participants were solely given a few hours to address this problem. In this paper, we describe the goal and the multi-phase organization of the hackathon; we describe the proposed methods and the on-site results. Additionally, we present post-competition results where we show how the presented methods perform on an independent set of lung cancer slides, which was not part of the initial competition, as well as a comparison on lymphocyte assessment between presented methods and a panel of pathologists. We show that some of the participants were capable to achieve pathologist-level performance at lymphocyte assessment. After the hackathon, LYSTO was left as a lightweight plug-and-play benchmark dataset on grand-challenge website, together with an automatic evaluation platform. LYSTO has supported a number of research in lymphocyte assessment in oncology. LYSTO will be a long-lasting educational challenge for deep learning and digital pathology, it is available at https://lysto.grand-challenge.org/.

Nuclear Segmentation and Classification: On Color & Compression Generalization

Since the introduction of digital and computational pathology as a field, one of the major problems in the clinical application of algorithms has been the struggle to generalize well to examples outside the distribution of the training data. Existing work to address this in both pathology and natural images has focused almost exclusively on classification tasks. We explore and evaluate the robustness of the 7 best performing nuclear segmentation and classification models from the largest computational pathology challenge for this problem to date, the CoNIC challenge. We demonstrate that existing state-of-the-art (SoTA) models are robust towards compression artifacts but suffer substantial performance reduction when subjected to shifts in the color domain. We find that using stain normalization to address the domain shift problem can be detrimental to the model performance. On the other hand, neural style transfer is more consistent in improving test performance when presented with large color variations in the wild.

Stain-Robust Mitotic Figure Detection for MIDOG 2022 Challenge

The detection of mitotic figures from different scanners/sites remains an important topic of research, owing to its potential in assisting clinicians with tumour grading. The MItosis DOmain Generalization (MIDOG) 2022 challenge aims to test the robustness of detection models on unseen data from multiple scanners and tissue types for this task. We present a short summary of the approach employed by the TIA Centre team to address this challenge. Our approach is based on a hybrid detection model, where mitotic candidates are segmented, before being refined by a deep learning classifier. Cross-validation on the training images achieved the F1-score of 0.816 and 0.784 on the preliminary test set, demonstrating the generalizability of our model to unseen data from new scanners.

TIAger: Tumor-Infiltrating Lymphocyte Scoring in Breast Cancer for the TiGER Challenge

The quantification of tumor-infiltrating lymphocytes (TILs) has been shown to be an independent predictor for prognosis of breast cancer patients. Typically, pathologists give an estimate of the proportion of the stromal region that contains TILs to obtain a TILs score. The Tumor InfiltratinG lymphocytes in breast cancER (TiGER) challenge, aims to assess the prognostic significance of computer-generated TILs scores for predicting survival as part of a Cox proportional hazards model. For this challenge, as the TIAger team, we have developed an algorithm to first segment tumor vs. stroma, before localising the tumor bulk region for TILs detection. Finally, we use these outputs to generate a TILs score for each case. On preliminary testing, our approach achieved a tumor-stroma weighted Dice score of 0.791 and a FROC score of 0.572 for lymphocytic detection. For predicting survival, our model achieved a C-index of 0.719. These results achieved first place across the preliminary testing leaderboards of the TiGER challenge.

Deep Feature based Cross-slide Registration

Cross-slide image analysis provides additional information by analysing the expression of different biomarkers as compared to a single slide analysis. Slides stained with different biomarkers are analysed side by side which may reveal unknown relations between the different biomarkers. During the slide preparation, a tissue section may be placed at an arbitrary orientation as compared to other sections of the same tissue block. The problem is compounded by the fact that tissue contents are likely to change from one section to the next and there may be unique artefacts on some of the slides. This makes registration of each section to a reference section of the same tissue block an important pre-requisite task before any cross-slide analysis. We propose a deep feature based registration (DFBR) method which utilises data-driven features to estimate the rigid transformation. We adopted a multi-stage strategy for improving the quality of registration. We also developed a visualisation tool to view registered pairs of WSIs at different magnifications. With the help of this tool, one can apply a transformation on the fly without the need to generate transformed source WSI in a pyramidal form. We compared the performance of data-driven features with that of hand-crafted features on the COMET dataset. Our approach can align the images with low registration errors. Generally, the success of non-rigid registration is dependent on the quality of rigid registration. To evaluate the efficacy of the DFBR method, the first two steps of the ANHIR winner's framework are replaced with our DFBR to register challenge provided image pairs. The modified framework produce comparable results to that of challenge winning team.

Deep Learning based Prediction of MSI in Colorectal Cancer via Prediction of the Status of MMR Markers

An accurate diagnosis and profiling of tumour are critical to the best treatment choices for cancer patients. In addition to the cancer type and its aggressiveness, molecular heterogeneity also plays a vital role in treatment selection. MSI or MMR deficiency is one of the well-studied aberrations in terms of molecular changes. Colorectal cancer patients with MMR deficiency respond well to immunotherapy, hence assessment of the relevant molecular markers can assist clinicians in making optimal treatment selections for patients. Immunohistochemistry is one of the ways for identifying these molecular changes which requires additional sections of tumour tissue. Introduction of automated methods that can predict MSI or MMR status from a target image without the need for additional sections can substantially reduce the cost associated with it. In this work, we present our work on predicting MSI status in a two-stage process using a single target slide either stained with CK818 or H\&E. First, we train a multi-headed convolutional neural network model where each head is responsible for predicting one of the MMR protein expressions. To this end, we perform registration of MMR slides to the target slide as a pre-processing step. In the second stage, statistical features computed from the MMR prediction maps are used for the final MSI prediction. Our results demonstrate that MSI classification can be improved on incorporating fine-grained MMR labels in comparison to the previous approaches in which coarse labels (MSI/MSS) are utilised.

Handcrafted Histological Transformer (H2T): Unsupervised Representation of Whole Slide Images

Diagnostic, prognostic and therapeutic decision-making of cancer in pathology clinics can now be carried out based on analysis of multi-gigapixel tissue images, also known as whole-slide images (WSIs). Recently, deep convolutional neural networks (CNNs) have been proposed to derive unsupervised WSI representations; these are attractive as they rely less on expert annotation which is cumbersome. However, a major trade-off is that higher predictive power generally comes at the cost of interpretability, posing a challenge to their clinical use where transparency in decision-making is generally expected. To address this challenge, we present a handcrafted framework based on deep CNN for constructing holistic WSI-level representations. Building on recent findings about the internal working of the Transformer in the domain of natural language processing, we break down its processes and handcraft them into a more transparent framework that we term as the Handcrafted Histological Transformer or H2T. Based on our experiments involving various datasets consisting of a total of 5,306 WSIs, the results demonstrate that H2T based holistic WSI-level representations offer competitive performance compared to recent state-of-the-art methods and can be readily utilized for various downstream analysis tasks. Finally, our results demonstrate that the H2T framework can be up to 14 times faster than the Transformer models.

CoNIC: Colon Nuclei Identification and Counting Challenge 2022

Nuclear segmentation, classification and quantification within Haematoxylin & Eosin stained histology images enables the extraction of interpretable cell-based features that can be used in downstream explainable models in computational pathology (CPath). However, automatic recognition of different nuclei is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intra-class variability. To help drive forward research and innovation for automatic nuclei recognition in CPath, we organise the Colon Nuclei Identification and Counting (CoNIC) Challenge. The challenge encourages researchers to develop algorithms that perform segmentation, classification and counting of nuclei within the current largest known publicly available nuclei-level dataset in CPath, containing around half a million labelled nuclei. Therefore, the CoNIC challenge utilises over 10 times the number of nuclei as the previous largest challenge dataset for nuclei recognition. It is important for algorithms to be robust to input variation if we wish to deploy them in a clinical setting. Therefore, as part of this challenge we will also test the sensitivity of each submitted algorithm to certain input variations.

FedDropoutAvg: Generalizable federated learning for histopathology image classification

Federated learning (FL) enables collaborative learning of a deep learning model without sharing the data of participating sites. FL in medical image analysis tasks is relatively new and open for enhancements. In this study, we propose FedDropoutAvg, a new federated learning approach for training a generalizable model. The proposed method takes advantage of randomness, both in client selection and also in federated averaging process. We compare FedDropoutAvg to several algorithms in an FL scenario for real-world multi-site histopathology image classification task. We show that with FedDropoutAvg, the final model can achieve performance better than other FL approaches and closer to a classical deep learning model that requires all data to be shared for centralized training. We test the trained models on a large dataset consisting of 1.2 million image tiles from 21 different centers. To evaluate the generalization ability of the proposed approach, we use held-out test sets from centers whose data was used in the FL and for unseen data from other independent centers whose data was not used in the federated training. We show that the proposed approach is more generalizable than other state-of-the-art federated training approaches. To the best of our knowledge, ours is the first study to use a randomized client and local model parameter selection procedure in a federated setting for a medical image analysis task.