arXiv subjects

Shan E Ahmed Raza

Publications and source records attributed to Shan E Ahmed Raza.

At least 37 records · Page 2Linked to original sources

arXiv2023

Domain Generalization in Computational Pathology: Survey and Guidelines

Deep learning models have exhibited exceptional effectiveness in Computational Pathology (CPath) by tackling intricate tasks across an array of histology image analysis applications. Nevertheless, the presence of out-of-distribution data (stemming from a multitude of sources such as disparate imaging devices and diverse tissue preparation methods) can cause \emph{domain shift} (DS). DS decreases the generalization of trained models to unseen datasets with slightly different data distributions, prompting the need for innovative \emph{domain generalization} (DG) solutions. Recognizing the potential of DG methods to significantly influence diagnostic and prognostic models in cancer studies and clinical practice, we present this survey along with guidelines on achieving DG in CPath. We rigorously define various DS types, systematically review and categorize existing DG approaches and resources in CPath, and provide insights into their advantages, limitations, and applicability. We also conduct thorough benchmarking experiments with 28 cutting-edge DG algorithms to address a complex DG problem. Our findings suggest that careful experiment design and CPath-specific Stain Augmentation technique can be very effective. However, there is no one-size-fits-all solution for DG in CPath. Therefore, we establish clear guidelines for detecting and managing DS depending on different scenarios. While most of the concepts, guidelines, and recommendations are given for applications in CPath, we believe that they are applicable to most medical image analysis tasks as well.

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arXiv2023

Mitosis Detection, Fast and Slow: Robust and Efficient Detection of Mitotic Figures

Counting of mitotic figures is a fundamental step in grading and prognostication of several cancers. However, manual mitosis counting is tedious and time-consuming. In addition, variation in the appearance of mitotic figures causes a high degree of discordance among pathologists. With advances in deep learning models, several automatic mitosis detection algorithms have been proposed but they are sensitive to {\em domain shift} often seen in histology images. We propose a robust and efficient two-stage mitosis detection framework, which comprises mitosis candidate segmentation ({\em Detecting Fast}) and candidate refinement ({\em Detecting Slow}) stages. The proposed candidate segmentation model, termed \textit{EUNet}, is fast and accurate due to its architectural design. EUNet can precisely segment candidates at a lower resolution to considerably speed up candidate detection. Candidates are then refined using a deeper classifier network, EfficientNet-B7, in the second stage. We make sure both stages are robust against domain shift by incorporating domain generalization methods. We demonstrate state-of-the-art performance and generalizability of the proposed model on the three largest publicly available mitosis datasets, winning the two mitosis domain generalization challenge contests (MIDOG21 and MIDOG22). Finally, we showcase the utility of the proposed algorithm by processing the TCGA breast cancer cohort (1,125 whole-slide images) to generate and release a repository of more than 620K mitotic figures.

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arXiv2023

A Fully Automated and Explainable Algorithm for the Prediction of Malignant Transformation in Oral Epithelial Dysplasia

Oral epithelial dysplasia (OED) is a premalignant histopathological diagnosis given to lesions of the oral cavity. Its grading suffers from significant inter-/intra- observer variability, and does not reliably predict malignancy progression, potentially leading to suboptimal treatment decisions. To address this, we developed a novel artificial intelligence algorithm that can assign an Oral Malignant Transformation (OMT) risk score, based on histological patterns in the in Haematoxylin and Eosin stained whole slide images, to quantify the risk of OED progression. The algorithm is based on the detection and segmentation of nuclei within (and around) the epithelium using an in-house segmentation model. We then employed a shallow neural network fed with interpretable morphological/spatial features, emulating histological markers. We conducted internal cross-validation on our development cohort (Sheffield; n = 193 cases) followed by independent validation on two external cohorts (Birmingham and Belfast; n = 92 cases). The proposed OMTscore yields an AUROC = 0.74 in predicting whether an OED progresses to malignancy or not. Survival analyses showed the prognostic value of our OMTscore for predicting malignancy transformation, when compared to the manually-assigned WHO and binary grades. Analysis of the correctly predicted cases elucidated the presence of peri-epithelial and epithelium-infiltrating lymphocytes in the most predictive patches of cases that transformed (p < 0.0001). This is the first study to propose a completely automated algorithm for predicting OED transformation based on interpretable nuclear features, whilst being validated on external datasets. The algorithm shows better-than-human-level performance for prediction of OED malignant transformation and offers a promising solution to the challenges of grading OED in routine clinical practice.

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arXiv2023

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/.

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arXiv2023

CoNIC Challenge: Pushing the Frontiers of Nuclear Detection, Segmentation, Classification and Counting

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery.

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arXiv2023

Consistency Regularisation in Varying Contexts and Feature Perturbations for Semi-Supervised Semantic Segmentation of Histology Images

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.

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arXiv2023

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.

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arXiv2022

One Model is All You Need: Multi-Task Learning Enables Simultaneous Histology Image Segmentation and Classification

The recent surge in performance for image analysis of digitised pathology slides can largely be attributed to the advances in deep learning. Deep models can be used to initially localise various structures in the tissue and hence facilitate the extraction of interpretable features for biomarker discovery. However, these models are typically trained for a single task and therefore scale poorly as we wish to adapt the model for an increasing number of different tasks. Also, supervised deep learning models are very data hungry and therefore rely on large amounts of training data to perform well. In this paper, we present a multi-task learning approach for segmentation and classification of nuclei, glands, lumina and different tissue regions that leverages data from multiple independent data sources. While ensuring that our tasks are aligned by the same tissue type and resolution, we enable meaningful simultaneous prediction with a single network. As a result of feature sharing, we also show that the learned representation can be used to improve the performance of additional tasks via transfer learning, including nuclear classification and signet ring cell detection. As part of this work, we train our developed Cerberus model on a huge amount of data, consisting of over 600K objects for segmentation and 440K patches for classification. We use our approach to process 599 colorectal whole-slide images from TCGA, where we localise 377 million, 900K and 2.1 million nuclei, glands and lumina, respectively and make the results available to the community for downstream analysis.

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arXiv2022

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.

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arXiv2022

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.

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arXiv2022

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. These biomarker stained slides are analysed side by side, revealing unknown relations between them. 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 produces comparable results to that of challenge winning team.

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arXiv2022

Deep Learning based Prediction of MSI using MMR Markers in Colorectal Cancer

The accurate diagnosis and molecular profiling of colorectal cancers are critical for planning the best treatment options for patients. Microsatellite instability (MSI) or mismatch repair (MMR) status plays a vital role in appropriate treatment selection, has prognostic implications and is used to investigate the possibility of patients having underlying genetic disorders (Lynch syndrome). NICE recommends that all CRC patients should be offered MMR/MSI testing. Immunohistochemistry is commonly used to assess MMR status with subsequent molecular testing performed as required. This incurs significant extra costs and requires additional resources. The introduction of automated methods that can predict MSI or MMR status from a target image could substantially reduce the cost associated with MMR testing. Unlike previous studies on MSI prediction involving training a CNN using coarse labels (MSI vs Microsatellite Stable (MSS)), we have utilised fine-grain MMR labels for training purposes. In this paper, we present our work on predicting MSI status in a two-stage process using a single target slide either stained with CK8/18 or H&E. First, we trained a multi-headed convolutional neural network model where each head was responsible for predicting one of the MMR protein expressions. To this end, we performed the registration of MMR stained slides to the target slide as a pre-processing step. In the second stage, statistical features computed from the MMR prediction maps were used for the final MSI prediction. Our results demonstrated that MSI classification can be improved by incorporating fine-grained MMR labels in comparison to the previous approaches in which only coarse labels were utilised.

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arXiv2021

Lizard: A Large-Scale Dataset for Colonic Nuclear Instance Segmentation and Classification

The development of deep segmentation models for computational pathology (CPath) can help foster the investigation of interpretable morphological biomarkers. Yet, there is a major bottleneck in the success of such approaches because supervised deep learning models require an abundance of accurately labelled data. This issue is exacerbated in the field of CPath because the generation of detailed annotations usually demands the input of a pathologist to be able to distinguish between different tissue constructs and nuclei. Manually labelling nuclei may not be a feasible approach for collecting large-scale annotated datasets, especially when a single image region can contain thousands of different cells. However, solely relying on automatic generation of annotations will limit the accuracy and reliability of ground truth. Therefore, to help overcome the above challenges, we propose a multi-stage annotation pipeline to enable the collection of large-scale datasets for histology image analysis, with pathologist-in-the-loop refinement steps. Using this pipeline, we generate the largest known nuclear instance segmentation and classification dataset, containing nearly half a million labelled nuclei in H&E stained colon tissue. We have released the dataset and encourage the research community to utilise it to drive forward the development of downstream cell-based models in CPath.

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arXiv2021

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.

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arXiv2021

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.

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arXiv2021

Semantic annotation for computational pathology: Multidisciplinary experience and best practice recommendations

Recent advances in whole slide imaging (WSI) technology have led to the development of a myriad of computer vision and artificial intelligence (AI) based diagnostic, prognostic, and predictive algorithms. Computational Pathology (CPath) offers an integrated solution to utilize information embedded in pathology WSIs beyond what we obtain through visual assessment. For automated analysis of WSIs and validation of machine learning (ML) models, annotations at the slide, tissue and cellular levels are required. The annotation of important visual constructs in pathology images is an important component of CPath projects. Improper annotations can result in algorithms which are hard to interpret and can potentially produce inaccurate and inconsistent results. Despite the crucial role of annotations in CPath projects, there are no well-defined guidelines or best practices on how annotations should be carried out. In this paper, we address this shortcoming by presenting the experience and best practices acquired during the execution of a large-scale annotation exercise involving a multidisciplinary team of pathologists, ML experts and researchers as part of the Pathology image data Lake for Analytics, Knowledge and Education (PathLAKE) consortium. We present a real-world case study along with examples of different types of annotations, diagnostic algorithm, annotation data dictionary and annotation constructs. The analyses reported in this work highlight best practice recommendations that can be used as annotation guidelines over the lifecycle of a CPath project.

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arXiv2021

A digital score of tumour-associated stroma infiltrating lymphocytes predicts survival in head and neck squamous cell carcinoma

The infiltration of T-lymphocytes in the stroma and tumour is an indication of an effective immune response against the tumour, resulting in better survival. In this study, our aim is to explore the prognostic significance of tumour-associated stroma infiltrating lymphocytes (TASILs) in head and neck squamous cell carcinoma (HNSCC) through an AI based automated method. A deep learning based automated method was employed to segment tumour, stroma and lymphocytes in digitally scanned whole slide images of HNSCC tissue slides. The spatial patterns of lymphocytes and tumour-associated stroma were digitally quantified to compute the TASIL-score. Finally, prognostic significance of the TASIL-score for disease-specific and disease-free survival was investigated with the Cox proportional hazard analysis. Three different cohorts of Haematoxylin & Eosin (H&E) stained tissue slides of HNSCC cases (n=537 in total) were studied, including publicly available TCGA head and neck cancer cases. The TASIL-score carries prognostic significance (p=0.002) for disease-specific survival of HNSCC patients. The TASIL-score also shows a better separation between low- and high-risk patients as compared to the manual TIL scoring by pathologists for both disease-specific and disease-free survival. A positive correlation of TASIL-score with molecular estimates of CD8+ T cells was also found, which is in line with existing findings. To the best of our knowledge, this is the first study to automate the quantification of TASIL from routine H&E slides of head and neck cancer. Our TASIL-score based findings are aligned with the clinical knowledge with the added advantages of objectivity, reproducibility and strong prognostic value. A comprehensive evaluation on large multicentric cohorts is required before the proposed digital score can be adopted in clinical practice.

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arXiv2020

HydraMix-Net: A Deep Multi-task Semi-supervised Learning Approach for Cell Detection and Classification

Semi-supervised techniques have removed the barriers of large scale labelled set by exploiting unlabelled data to improve the performance of a model. In this paper, we propose a semi-supervised deep multi-task classification and localization approach HydraMix-Net in the field of medical imagining where labelling is time consuming and costly. Firstly, the pseudo labels are generated using the model's prediction on the augmented set of unlabelled image with averaging. The high entropy predictions are further sharpened to reduced the entropy and are then mixed with the labelled set for training. The model is trained in multi-task learning manner with noise tolerant joint loss for classification localization and achieves better performance when given limited data in contrast to a simple deep model. On DLBCL data it achieves 80\% accuracy in contrast to simple CNN achieving 70\% accuracy when given only 100 labelled examples.

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