Deep-learning methods for computational pathology require either manual annotation of gigapixel whole-slide images (WSIs) or large datasets of WSIs with slide-level labels and typically suffer from poor domain adaptation and interpretability. Here we report an interpretable weakly supervised deep-learning method for data-efficient WSI processing and learning that only requires slide-level labels. The method, which we named clustering-constrained-attention multiple-instance learning (CLAM), uses attention-based learning to identify subregions of high diagnostic value to accurately classify whole slides and instance-level clustering over the identified representative regions to constrain and refine the feature space. By applying CLAM to the subtyping of renal cell carcinoma and non-small-cell lung cancer as well as the detection of lymph node metastasis, we show that it can be used to localize well-known morphological features on WSIs without the need for spatial labels, that it overperforms standard weakly supervised classification algorithms and that it is adaptable to independent test cohorts, smartphone microscopy and varying tissue content.

Data-efficient and weakly supervised computational pathology on whole-slide images.

Annotating videos is cumbersome, expensive and not scalable. Yet, many strong video models still rely on manually annotated data. With the recent introduction of the HowTo100M dataset, narrated videos now offer the possibility of learning video representations without manual supervision. In this work we propose a new learning approach, MIL-NCE, capable of addressing mis- alignments inherent in narrated videos. With this approach we are able to learn strong video representations from scratch, without the need for any manual annotation. We evaluate our representations on a wide range of four downstream tasks over eight datasets: action recognition (HMDB-51, UCF-101, Kinetics-700), text-to- video retrieval (YouCook2, MSR-VTT), action localization (YouTube-8M Segments, CrossTask) and action segmentation (COIN). Our method outperforms all published self-supervised approaches for these tasks as well as several fully supervised baselines.

/pdf/end-to-end-learning-of-visual-representations-from-uncurated-1x45g7p9jo.pdf

End-to-End Learning of Visual Representations From Uncurated Instructional Videos

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.

pdf/data-efficient-and-weakly-supervised-computational-pathology-59gcyo4nge.pdf

Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images

Not-so-supervised: A survey of semi-supervised, multi-instance, and transfer learning in medical image analysis

The goal of domain generalization algorithms is to predict well on distributions different from those seen during training While a myriad of domain generalization algorithms exist, inconsistencies in experimental conditions -- datasets, architectures, and model selection criteria -- render fair and realistic comparisons difficult In this paper, we are interested in understanding how useful domain generalization algorithms are in realistic settings As a first step, we realize that model selection is non-trivial for domain generalization tasks Contrary to prior work, we argue that domain generalization algorithms without a model selection strategy should be regarded as incomplete Next, we implement DomainBed, a testbed for domain generalization including seven multi-domain datasets, nine baseline algorithms, and three model selection criteria We conduct extensive experiments using DomainBed and find that, when carefully implemented, empirical risk minimization shows state-of-the-art performance across all datasets Looking forward, we hope that the release of DomainBed, along with contributions from fellow researchers, will streamline reproducible and rigorous research in domain generalization

In Search of Lost Domain Generalization

Multiple instance learning (MIL) is a variation of supervised learning where a single class label is assigned to a bag of instances. In this paper, we state the MIL problem as learning the Bernoulli distribution of the bag label where the bag label probability is fully parameterized by neural networks. Furthermore, we propose a neural network-based permutation-invariant aggregation operator that corresponds to the attention mechanism. Notably, an application of the proposed attention-based operator provides insight into the contribution of each instance to the bag label. We show empirically that our approach achieves comparable performance to the best MIL methods on benchmark MIL datasets and it outperforms other methods on a MNIST-based MIL dataset and two real-life histopathology datasets without sacrificing interpretability.

/pdf/attention-based-deep-multiple-instance-learning-2wobm70rej.pdf

Attention-based Deep Multiple Instance Learning

We consider the problem of domain generalization, namely, how to learn representations given data from a set of domains that generalize to data from a previously unseen domain. We propose the Domain Invariant Variational Autoencoder (DIVA), a generative model that tackles this problem by learning three independent latent subspaces, one for the domain, one for the class, and one for any residual variations. We highlight that due to the generative nature of our model we can also incorporate unlabeled data from known or previously unseen domains. To the best of our knowledge this has not been done before in a domain generalization setting. This property is highly desirable in fields like medical imaging where labeled data is scarce. We experimentally evaluate our model on the rotated MNIST benchmark and a malaria cell images dataset where we show that (i) the learned subspaces are indeed complementary to each other, (ii) we improve upon recent works on this task and (iii) incorporating unlabelled data can boost the performance even further.

DIVA: Domain Invariant Variational Autoencoders

Self-supervised learning in vision-language processing exploits semantic alignment between imaging and text modalities. Prior work in biomedical VLP has mostly relied on the alignment of single image and report pairs even though clinical notes commonly refer to prior images. This does not only introduce poor alignment between the modalities but also a missed opportunity to exploit rich self-supervision through existing temporal content in the data. In this work, we explicitly account for prior images and reports when available during both training and fine-tuning. Our approach, named BioViL-T, uses a CNN-Transformer hybrid multi-image encoder trained jointly with a text model. It is designed to be versatile to arising challenges such as pose variations and missing input images across time. The resulting model excels on downstream tasks both in single- and multi-image setups, achieving state-of-the-art performance on (I) progression classification, (II) phrase grounding, and (III) report generation, whilst offering consistent improvements on disease classification and sentence-similarity tasks. We release a novel multi-modal temporal benchmark dataset, MS-CXR-T, to quantify the quality of vision-language representations in terms of temporal semantics. Our experimental results show the advantages of incorporating prior images and reports to make most use of the data.

Learning to Exploit Temporal Structure for Biomedical Vision-Language Processing

We consider the problem of domain generalization, namely, how to learn representations given data from a set of domains that generalize to data from a previously unseen domain. We propose the domain invariant VAE (DIVA), a generative model that tackles this problem by learning three independent latent subspaces, one for the class, one for the domain and one for the object itself. In addition, we highlight that due to the generative nature of our model we can also incorporate unlabeled data from known or previously unseen domains. This property is highly desirable in fields like medical imaging where labeled data is scarce. We experimentally evaluate our model on the rotated MNIST benchmark where we show that (i) the learned subspaces are indeed complementary to each other, (ii) we improve upon recent works on this task and (iii) incorporating unlabelled data can boost the performance even further. © Deep Generative Models for Highly Structured Data, DGS@ICLR 2019 Workshop.All right reserved.

/pdf/diva-domain-invariant-variational-autoencoders-3vstc2h5kt.pdf

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Attention-based Deep Multiple Instance Learning

Attention-based Deep Multiple Instance Learning

DIVA: Domain Invariant Variational Autoencoders

Learning to Exploit Temporal Structure for Biomedical Vision-Language Processing

DIVA: Domain Invariant Variational Autoencoders