Deep-Learning for Classification of Colorectal Polyps on Whole-Slide Images

Histopathological characterization of colorectal polyps is an important principle for determining the risk of colorectal cancer and future rates of surveillance for patients. This characterization is time-intensive, requires years of specialized training, and suffers from significant inter-observer and intra-observer variability. In this work, we built an automatic image-understanding method that can accurately classify different types of colorectal polyps in whole-slide histology images to help pathologists with histopathological characterization and diagnosis of colorectal polyps. The proposed image-understanding method is based on deep-learning techniques, which rely on numerous levels of abstraction for data representation and have shown state-of-the-art results for various image analysis tasks. Our image-understanding method covers all five polyp types (hyperplastic polyp, sessile serrated polyp, traditional serrated adenoma, tubular adenoma, and tubulovillous/villous adenoma) that are included in the US multi-society task force guidelines for colorectal cancer risk assessment and surveillance, and encompasses the most common occurrences of colorectal polyps. Our evaluation on 239 independent test samples shows our proposed method can identify the types of colorectal polyps in whole-slide images with a high efficacy (accuracy: 93.0%, precision: 89.7%, recall: 88.3%, F1 score: 88.8%). The presented method in this paper can reduce the cognitive burden on pathologists and improve their accuracy and efficiency in histopathological characterization of colorectal polyps, and in subsequent risk assessment and follow-up recommendations

Translating AI to digital pathology workflow: Dealing with scarce data and high variation by minimising complexities in data and models

The recent conversion to digital pathology using Whole Slide Images (WSIs) from conventional pathology opened the doors for Artificial Intelligence (AI) in pathology workflow. The recent interests in machine learning and deep learning have gained a high interest in medical image processing. However, WSIs differ from generic medical images. WSIs are complex images which can reveal various information to support different diagnosis varying from cancer to unknown underlying conditions which were not discovered in other medical investigations. These investigations require expert knowledge spending a long time for investigations, applying different stains to the WSIs, and comparing the WSIs. Differences in WSI differentiate general machine learning methods that are applied for medical image processing. Co-analysing multistained WSIs, high variation of the WSIs from different sites, and lack of labelled data are the main key interest areas that directly influence in developing machine learning models that support pathologists in their investigations. However, most of the state-ofthe- art machine learning approaches cannot be applied in the general clinical workflow without using high compute power, expert knowledge, and time. Therefore, this thesis explores avenues to translate the highly computational and time intensive model to a clinical workflow. Co-analysing multi-stained WSIs require registering differently stained WSI together. In order to get a high precision in the registration exploring nonrigid and rigid transformation is required. The non-rigid transformation requires complex deep learning approaches. Using super-convergence on a small Convolutional Neural Network model it is possible to achieve high precision compared to larger auto-encoders and other state-of-the-art models. High variation of the WSIs from different sites heavily effect machine learning models in their predictions. The thesis presents an approach of using a pre-trained model by using only a small number of samples from the new site. Therefore, re-training larger deep learning models are not required which saves expert time for re-labelling and computational power. Finally, lack of labelled data is one of the main issues in training any supervised machine learning or deep learning model. Using a Generative Adversarial Networks (GAN) is an approach which can be easily implemented to avoid this issue. However, GANs are time and computationally expensive. These are not applicable in a general clinical workflow. Therefore, this thesis presents an approach using a simpler GANthat can generate accurate sample labelled data. The synthetic data are used to train classifier and the thesis demonstrates that the predictive model can generate higher accuracy in the test environment. This thesis demonstrates that machine learning and deep learning models can be applied to a clinical workflow, without exploiting expert time and high computing power

Artificial intelligence in digital pathology: a diagnostic test accuracy systematic review and meta-analysis

Ensuring diagnostic performance of AI models before clinical use is key to the safe and successful adoption of these technologies. Studies reporting AI applied to digital pathology images for diagnostic purposes have rapidly increased in number in recent years. The aim of this work is to provide an overview of the diagnostic accuracy of AI in digital pathology images from all areas of pathology. This systematic review and meta-analysis included diagnostic accuracy studies using any type of artificial intelligence applied to whole slide images (WSIs) in any disease type. The reference standard was diagnosis through histopathological assessment and / or immunohistochemistry. Searches were conducted in PubMed, EMBASE and CENTRAL in June 2022. We identified 2976 studies, of which 100 were included in the review and 48 in the full meta-analysis. Risk of bias and concerns of applicability were assessed using the QUADAS-2 tool. Data extraction was conducted by two investigators and meta-analysis was performed using a bivariate random effects model. 100 studies were identified for inclusion, equating to over 152,000 whole slide images (WSIs) and representing many disease types. Of these, 48 studies were included in the meta-analysis. These studies reported a mean sensitivity of 96.3% (CI 94.1-97.7) and mean specificity of 93.3% (CI 90.5-95.4) for AI. There was substantial heterogeneity in study design and all 100 studies identified for inclusion had at least one area at high or unclear risk of bias. This review provides a broad overview of AI performance across applications in whole slide imaging. However, there is huge variability in study design and available performance data, with details around the conduct of the study and make up of the datasets frequently missing. Overall, AI offers good accuracy when applied to WSIs but requires more rigorous evaluation of its performance.Comment: 26 pages, 5 figures, 8 tables + Supplementary material

Automatic recognition of different types of acute leukaemia using peripheral blood cell images

[eng] Clinical pathologists have learned to identify morphological qualitative features to characterise the different normal cells, as well as the abnormal cell types whose presence in peripheral blood is the evidence of serious haematological diseases. A drawback of visual morphological analysis is that is time consuming, requires well-trained personnel and is prone to intra-observer variability, which is particularly true when dealing with blast cells. Indeed, subtle interclass morphological differences exist for leukaemia types, which turns into low specificity scores in the routine screening. They are well-known the difficulties that clinical pathologists have in the discrimination among different blasts and the subjectivity associated with their morphological recognition. The general objective of this thesis is the automatic recognition of different types of blast cells circulating in peripheral blood in acute leukaemia using digital image processing and machine learning techniques. In order to accomplish this objective, this thesis starts with a discrimination among normal mononuclear cells, reactive lymphocytes and three types of leukemic cells using traditional machine learning techniques and hand-crafted features obtained from cell segmentation. In the second part of the thesis, a new predictive system designed with two serially connected convolutional neural networks is developed for the diagnosis of acute leukaemia. This system was proved to distinguish neoplastic (leukaemia) and non-neoplastic (infections) diseases, as well as recognise the leukaemia lineage. Furthermore, it was evaluated for its integration in a real-clinical setting. This thesis also contributes in advancing the state of the art of the automatic recognition of acute leukaemia by providing a more realistic approach which reflects the real-life complexity of acute leukaemia diagnosis

Histological classification of canine and feline lymphoma using a modular approach based on deep learning and advanced image processing

Histopathological examination of tissue samples is essential for identifying tumor malignancy and the diagnosis of different types of tumor. In the case of lymphoma classification, nuclear size of the neoplastic lymphocytes is one of the key features to differentiate the different subtypes. Based on the combination of artificial intelligence and advanced image processing, we provide a workflow for the classification of lymphoma with regards to their nuclear size (small, intermediate, and large). As the baseline for our workflow testing, we use a Unet++ model trained on histological images of canine lymphoma with individually labeled nuclei. As an alternative to the Unet++, we also used a publicly available pre-trained and unmodified instance segmentation model called Stardist to demonstrate that our modular classification workflow can be combined with different types of segmentation models if they can provide proper nuclei segmentation. Subsequent to nuclear segmentation, we optimize algorithmic parameters for accurate classification of nuclear size using a newly derived reference size and final image classification based on a pathologists-derived ground truth. Our image classification module achieves a classification accuracy of up to 92% on canine lymphoma data. Compared to the accuracy ranging from 66.67 to 84% achieved using measurements provided by three individual pathologists, our algorithm provides a higher accuracy level and reproducible results. Our workflow also demonstrates a high transferability to feline lymphoma, as shown by its accuracy of up to 84.21%, even though our workflow was not optimized for feline lymphoma images. By determining the nuclear size distribution in tumor areas, our workflow can assist pathologists in subtyping lymphoma based on the nuclei size and potentially improve reproducibility. Our proposed approach is modular and comprehensible, thus allowing adaptation for specific tasks and increasing the users’ trust in computer-assisted image classification

Case-based similar image retrieval for weakly annotated large histopathological images of malignant lymphoma using deep metric learning

In the present study, we propose a novel case-based similar image retrieval (SIR) method for hematoxylin and eosin (H&E)-stained histopathological images of malignant lymphoma. When a whole slide image (WSI) is used as an input query, it is desirable to be able to retrieve similar cases by focusing on image patches in pathologically important regions such as tumor cells. To address this problem, we employ attention-based multiple instance learning, which enables us to focus on tumor-specific regions when the similarity between cases is computed. Moreover, we employ contrastive distance metric learning to incorporate immunohistochemical (IHC) staining patterns as useful supervised information for defining appropriate similarity between heterogeneous malignant lymphoma cases. In the experiment with 249 malignant lymphoma patients, we confirmed that the proposed method exhibited higher evaluation measures than the baseline case-based SIR methods. Furthermore, the subjective evaluation by pathologists revealed that our similarity measure using IHC staining patterns is appropriate for representing the similarity of H&E-stained tissue images for malignant lymphoma