Computer-aided analysis of biological images typically requires extensive training on large-scale annotated datasets, which is not viable in many situations. In this paper we present GAN-DL, a Discriminator Learner based on the StyleGAN2 architecture, which we employ for self-supervised image representation learning in the case of fluorescent biological images. We show that Wasserstein Generative Adversarial Networks combined with linear Support Vector Machines enable high-throughput compound screening based on raw images. We demonstrate this by classifying active and inactive compounds tested for the inhibition of SARS-CoV-2 infection in VERO and HRCE cell lines. In contrast to previous methods, our deep learning based approach does not require any annotation besides the one that is normally collected during the sample preparation process. We test our technique on the RxRx19a Sars-CoV-2 image collection. The dataset consists of fluorescent images that were generated to assess the ability of regulatory-approved or in late-stage clinical trials compound to modulate the in vitro infection from SARS-CoV-2 in both VERO and HRCE cell lines. We show that our technique can be exploited not only for classification tasks, but also to effectively derive a dose response curve for the tested treatments, in a self-supervised manner. Lastly, we demonstrate its generalization capabilities by successfully addressing a zero-shot learning task, consisting in the categorization of four different cell types of the RxRx1 fluorescent images collection.
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Automatic medical image segmentation plays a critical role in scientific research and medical care. Existing high-performance deep learning methods typically rely on large training datasets with high-quality manual annotations, which are difficult to obtain in many clinical applications. Here, we introduce Annotation-effIcient Deep lEarning (AIDE), an open-source framework to handle imperfect training datasets. Methodological analyses and empirical evaluations are conducted, and we demonstrate that AIDE surpasses conventional fully-supervised models by presenting better performance on open datasets possessing scarce or noisy annotations. We further test AIDE in a real-life case study for breast tumor segmentation. Three datasets containing 11,852 breast images from three medical centers are employed, and AIDE, utilizing 10% training annotations, consistently produces segmentation maps comparable to those generated by fully-supervised counterparts or provided by independent radiologists. The 10-fold enhanced efficiency in utilizing expert labels has the potential to promote a wide range of biomedical applications.
Annotating cancerous regions in whole-slide images (WSIs) of pathology samples plays a critical role in clinical diagnosis, biomedical research, and machine learning algorithms development. However, generating exhaustive and accurate annotations is labor-intensive, challenging, and costly. Drawing only coarse and approximate annotations is a much easier task, less costly, and it alleviates pathologists' workload. In this paper, we study the problem of refining these approximate annotations in digital pathology to obtain more accurate ones. Some previous works have explored obtaining machine learning models from these inaccurate annotations, but few of them tackle the refinement problem where the mislabeled regions should be explicitly identified and corrected, and all of them require a - often very large - number of training samples. We present a method, named Label Cleaning Multiple Instance Learning (LC-MIL), to refine coarse annotations on a single WSI without the need of external training data. Patches cropped from a WSI with inaccurate labels are processed jointly with a MIL framework, and a deep-attention mechanism is leveraged to discriminate mislabeled instances, mitigating their impact on the predictive model and refining the segmentation. Our experiments on a heterogeneous WSI set with breast cancer lymph node metastasis, liver cancer, and colorectal cancer samples show that LC-MIL significantly refines the coarse annotations, outperforming the state-of-the-art alternatives, even while learning from a single slide. These results demonstrate the LC-MIL is a promising, lightweight tool to provide fine-grained annotations from coarsely annotated pathology sets.
Drug Discovery is a fundamental and ever-evolving field of research. The design of new candidate molecules requires large amounts of time and money, and computational methods are being increasingly employed to cut these costs. Machine learning methods are ideal for the design of large amounts of potential new candidate molecules, which are naturally represented as graphs. Graph generation is being revolutionized by deep learning methods, and molecular generation is one of its most promising applications. In this paper, we introduce a sequential molecular graph generator based on a set of graph neural network modules, which we call MG^2N^2. At each step, a node or a group of nodes is added to the graph, along with its connections. The modular architecture simplifies the training procedure, also allowing an independent retraining of a single module. Sequentiality and modularity make the generation process interpretable. The use of graph neural networks maximizes the information in input at each generative step, which consists of the subgraph produced during the previous steps. Experiments of unconditional generation on the QM9 and Zinc datasets show that our model is capable of generalizing molecular patterns seen during the training phase, without overfitting. The results indicate that our method is competitive, and outperforms challenging baselines for unconditional generation.
The key challenge in learning dense correspondences lies in the lack of ground-truth matches for real image pairs. While photometric consistency losses provide unsupervised alternatives, they struggle with large appearance changes, which are ubiquitous in geometric and semantic matching tasks. Moreover, methods relying on synthetic training pairs often suffer from poor generalisation to real data. We propose Warp Consistency, an unsupervised learning objective for dense correspondence regression. Our objective is effective even in settings with large appearance and view-point changes. Given a pair of real images, we first construct an image triplet by applying a randomly sampled warp to one of the original images. We derive and analyze all flow-consistency constraints arising between the triplet. From our observations and empirical results, we design a general unsupervised objective employing two of the derived constraints. We validate our warp consistency loss by training three recent dense correspondence networks for the geometric and semantic matching tasks. Our approach sets a new state-of-the-art on several challenging benchmarks, including MegaDepth, RobotCar and TSS. Code and models will be released at //github.com/PruneTruong/DenseMatching.
Deep supervised learning has achieved great success in the last decade. However, its deficiencies of dependence on manual labels and vulnerability to attacks have driven people to explore a better solution. As an alternative, self-supervised learning attracts many researchers for its soaring performance on representation learning in the last several years. Self-supervised representation learning leverages input data itself as supervision and benefits almost all types of downstream tasks. In this survey, we take a look into new self-supervised learning methods for representation in computer vision, natural language processing, and graph learning. We comprehensively review the existing empirical methods and summarize them into three main categories according to their objectives: generative, contrastive, and generative-contrastive (adversarial). We further investigate related theoretical analysis work to provide deeper thoughts on how self-supervised learning works. Finally, we briefly discuss open problems and future directions for self-supervised learning. An outline slide for the survey is provided.
Contrastive learning (CL) is a popular technique for self-supervised learning (SSL) of visual representations. It uses pairs of augmentations of unlabeled training examples to define a classification task for pretext learning of a deep embedding. Despite extensive works in augmentation procedures, prior works do not address the selection of challenging negative pairs, as images within a sampled batch are treated independently. This paper addresses the problem, by introducing a new family of adversarial examples for constrastive learning and using these examples to define a new adversarial training algorithm for SSL, denoted as CLAE. When compared to standard CL, the use of adversarial examples creates more challenging positive pairs and adversarial training produces harder negative pairs by accounting for all images in a batch during the optimization. CLAE is compatible with many CL methods in the literature. Experiments show that it improves the performance of several existing CL baselines on multiple datasets.
A key requirement for the success of supervised deep learning is a large labeled dataset - a condition that is difficult to meet in medical image analysis. Self-supervised learning (SSL) can help in this regard by providing a strategy to pre-train a neural network with unlabeled data, followed by fine-tuning for a downstream task with limited annotations. Contrastive learning, a particular variant of SSL, is a powerful technique for learning image-level representations. In this work, we propose strategies for extending the contrastive learning framework for segmentation of volumetric medical images in the semi-supervised setting with limited annotations, by leveraging domain-specific and problem-specific cues. Specifically, we propose (1) novel contrasting strategies that leverage structural similarity across volumetric medical images (domain-specific cue) and (2) a local version of the contrastive loss to learn distinctive representations of local regions that are useful for per-pixel segmentation (problem-specific cue). We carry out an extensive evaluation on three Magnetic Resonance Imaging (MRI) datasets. In the limited annotation setting, the proposed method yields substantial improvements compared to other self-supervision and semi-supervised learning techniques. When combined with a simple data augmentation technique, the proposed method reaches within 8% of benchmark performance using only two labeled MRI volumes for training, corresponding to only 4% (for ACDC) of the training data used to train the benchmark.
In this paper, we describe how to apply image-to-image translation techniques to medical blood smear data to generate new data samples and meaningfully increase small datasets. Specifically, given the segmentation mask of the microscopy image, we are able to generate photorealistic images of blood cells which are further used alongside real data during the network training for segmentation and object detection tasks. This image data generation approach is based on conditional generative adversarial networks which have proven capabilities to high-quality image synthesis. In addition to synthesizing blood images, we synthesize segmentation mask as well which leads to a diverse variety of generated samples. The effectiveness of the technique is thoroughly analyzed and quantified through a number of experiments on a manually collected and annotated dataset of blood smear taken under a microscope.
We address the problem of segmenting 3D multi-modal medical images in scenarios where very few labeled examples are available for training. Leveraging the recent success of adversarial learning for semi-supervised segmentation, we propose a novel method based on Generative Adversarial Networks (GANs) to train a segmentation model with both labeled and unlabeled images. The proposed method prevents over-fitting by learning to discriminate between true and fake patches obtained by a generator network. Our work extends current adversarial learning approaches, which focus on 2D single-modality images, to the more challenging context of 3D volumes of multiple modalities. The proposed method is evaluated on the problem of segmenting brain MRI from the iSEG-2017 and MRBrainS 2013 datasets. Significant performance improvement is reported, compared to state-of-art segmentation networks trained in a fully-supervised manner. In addition, our work presents a comprehensive analysis of different GAN architectures for semi-supervised segmentation, showing recent techniques like feature matching to yield a higher performance than conventional adversarial training approaches. Our code is publicly available at //github.com/arnab39/FewShot_GAN-Unet3D
Surgical data science is a new research field that aims to observe all aspects and factors of the patient treatment process in order to provide the right assistance to the right person at the right time. Due to the breakthrough successes of deep learning-based solutions for automatic image annotation, the availability of reference annotations for algorithm training is becoming a major bottleneck in the field. The purpose of this paper was to investigate the concept of self-supervised learning to address this issue. Our approach is guided by the hypothesis that unlabeled video data can be used to learn a representation of the target domain that boosts the performance of state-of-the-art machine learning algorithms when used for pre-training. Essentially, this method involves an auxiliary task that requires training with unlabeled endoscopic video data from the target domain to initialize a convolutional neural network (CNN) for the target task. In this paper, we propose to undertake a re-colorization of medical images with generative adversarial network (GAN)-based architecture as an auxiliary task. A variant of the method involves a second pre-training step based on labeled data for the target task from a related domain. We have validated both variants using medical instrument segmentation as the target task. The proposed approach can be used to radically reduce the manual annotation effort involved in training CNNs. Compared to the baseline approach of generating annotated data from scratch, our method decreases exploratively the number of labeled images by up to 60% without sacrificing performance. Our method also outperforms alternative methods for CNN pre-training, such as pre-training on publicly available non-medical (COCO) or medical data (MICCAI endoscopic vision challenge 2017) using the target task (in this instance: segmentation).
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