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Register a new userDeepSMILE: Self-supervised heterogeneity-aware multiple instance learning for DNA damage response defect classification directly from H&E whole-slide images
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We propose a Deep learning-based weak label learning method for analysing whole slide images (WSIs) of Hematoxylin and Eosin (H&E) stained tumorcells not requiring pixel-level or tile-level annotations using Self-supervised pre-training and heterogeneity-aware deep Multiple Instance LEarning (DeepSMILE). We apply DeepSMILE to the task of Homologous recombination deficiency (HRD) and microsatellite instability (MSI) prediction. We utilize contrastive self-supervised learning to pre-train a feature extractor on histopathology tiles of cancer tissue. Additionally, we use variability-aware deep multiple instance learning to learn the tile feature aggregation function while modeling tumor heterogeneity. Compared to state-of-the-art genomic label classification methods, DeepSMILE improves classification performance for HRD from $70.43pm4.10%$ to $83.79pm1.25%$ AUC and MSI from $78.56pm6.24%$ to $90.32pm3.58%$ AUC in a multi-center breast and colorectal cancer dataset, respectively. These improvements suggest we can improve genomic label classification performance without collecting larger datasets. In the future, this may reduce the need for expensive genome sequencing techniques, provide personalized therapy recommendations based on widely available WSIs of cancer tissue, and improve patient care with quicker treatment decisions - also in medical centers without access to genome sequencing resources.
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Multiple instance learning (MIL) is the preferred approach for whole slide image classification. However, most MIL approaches do not exploit the interdependencies of tiles extracted from a whole slide image, which could provide valuable cues for classification. This paper presents a novel MIL approach that exploits the spatial relationship of tiles for classifying whole slide images. To do so, a sparse map is built from tiles embeddings, and is then classified by a sparse-input CNN. It obtained state-of-the-art performance over popular MIL approaches on the classification of cancer subtype involving 10000 whole slide images. Our results suggest that the proposed approach might (i) improve the representation learning of instances and (ii) exploit the context of instance embeddings to enhance the classification performance. The code of this work is open-source at {github censored for review}.
Ovarian cancer is the most lethal cancer of the female reproductive organs. There are $5$ major histological subtypes of epithelial ovarian cancer, each with distinct morphological, genetic, and clinical features. Currently, these histotypes are determined by a pathologists microscopic examination of tumor whole-slide images (WSI). This process has been hampered by poor inter-observer agreement (Cohens kappa $0.54$-$0.67$). We utilized a textit{two}-stage deep transfer learning algorithm based on convolutional neural networks (CNN) and progressive resizing for automatic classification of epithelial ovarian carcinoma WSIs. The proposed algorithm achieved a mean accuracy of $87.54%$ and Cohens kappa of $0.8106$ in the slide-level classification of $305$ WSIs; performing better than a standard CNN and pathologists without gynecology-specific training.
Deep Learning-based computational pathology algorithms have demonstrated profound ability to excel in a wide array of tasks that range from characterization of well known morphological phenotypes to predicting non-human-identifiable features from histology such as molecular alterations. However, the development of robust, adaptable, and accurate deep learning-based models often rely on the collection and time-costly curation large high-quality annotated training data that should ideally come from diverse sources and patient populations to cater for the heterogeneity that exists in such datasets. Multi-centric and collaborative integration of medical data across multiple institutions can naturally help overcome this challenge and boost the model performance but is limited by privacy concerns amongst other difficulties that may arise in the complex data sharing process as models scale towards using hundreds of thousands of gigapixel whole slide images. In this paper, we introduce privacy-preserving federated learning for gigapixel whole slide images in computational pathology using weakly-supervised attention multiple instance learning and differential privacy. We evaluated our approach on two different diagnostic problems using thousands of histology whole slide images with only slide-level labels. Additionally, we present a weakly-supervised learning framework for survival prediction and patient stratification from whole slide images and demonstrate its effectiveness in a federated setting. Our results show that using federated learning, we can effectively develop accurate weakly supervised deep learning models from distributed data silos without direct data sharing and its associated complexities, while also preserving differential privacy using randomized noise generation.
The rapidly emerging field of computational pathology has the potential to enable objective diagnosis, therapeutic response prediction and identification of new morphological features of clinical relevance. However, deep learning-based computational pathology approaches either require manual annotation of gigapixel whole slide images (WSIs) in fully-supervised settings or thousands of WSIs with slide-level labels in a weakly-supervised setting. Moreover, whole slide level computational pathology methods also suffer from domain adaptation and interpretability issues. These challenges have prevented the broad adaptation of computational pathology for clinical and research purposes. Here we present CLAM - Clustering-constrained attention multiple instance learning, an easy-to-use, high-throughput, and interpretable WSI-level processing and learning method that only requires slide-level labels while being data efficient, adaptable and capable of handling multi-class subtyping problems. CLAM is a deep-learning-based weakly-supervised method that uses attention-based learning to automatically identify sub-regions of high diagnostic value in order to accurately classify the whole slide, while also utilizing instance-level clustering over the representative regions identified to constrain and refine the feature space. In three separate analyses, we demonstrate the data efficiency and adaptability of CLAM and its superior performance over standard weakly-supervised classification. We demonstrate that CLAM models are interpretable and can be used to identify well-known and new morphological features. We further show that models trained using CLAM are adaptable to independent test cohorts, cell phone microscopy images, and biopsies. CLAM is a general-purpose and adaptable method that can be used for a variety of different computational pathology tasks in both clinical and research settings.
The application of deep learning to pathology assumes the existence of digital whole slide images of pathology slides. However, slide digitization is bottlenecked by the high cost of precise motor stages in slide scanners that are needed for position information used for slide stitching. We propose GloFlow, a two-stage method for creating a whole slide image using optical flow-based image registration with global alignment using a computationally tractable graph-pruning approach. In the first stage, we train an optical flow predictor to predict pairwise translations between successive video frames to approximate a stitch. In the second stage, this approximate stitch is used to create a neighborhood graph to produce a corrected stitch. On a simulated dataset of video scans of WSIs, we find that our method outperforms known approaches to slide-stitching, and stitches WSIs resembling those produced by slide scanners.
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