Automatic identification of chemical moieties.

In recent years, the prediction of quantum mechanical observables with machine learning methods has become increasingly popular. Message-passing neural networks (MPNNs) solve this task by constructing atomic representations, from which the properties of interest are predicted. Here, we introduce a method to automatically identify chemical moieties (molecular building blocks) from such representations, enabling a variety of applications beyond property prediction, which otherwise rely on expert knowledge. The required representation can either be provided by a pretrained MPNN, or be learned from scratch using only structural information. Beyond the data-driven design of molecular fingerprints, the versatility of our approach is demonstrated by enabling the selection of representative entries in chemical databases, the automatic construction of coarse-grained force fields, as well as the identification of reaction coordinates.

Analysis of Deep Convolutional Neural Networks Using Tensor Kernels and Matrix-Based Entropy.

Analyzing deep neural networks (DNNs) via information plane (IP) theory has gained tremendous attention recently to gain insight into, among others, DNNs' generalization ability. However, it is by no means obvious how to estimate the mutual information (MI) between each hidden layer and the input/desired output to construct the IP. For instance, hidden layers with many neurons require MI estimators with robustness toward the high dimensionality associated with such layers. MI estimators should also be able to handle convolutional layers while at the same time being computationally tractable to scale to large networks. Existing IP methods have not been able to study truly deep convolutional neural networks (CNNs). We propose an IP analysis using the new matrix-based Rényi's entropy coupled with tensor kernels, leveraging the power of kernel methods to represent properties of the probability distribution independently of the dimensionality of the data. Our results shed new light on previous studies concerning small-scale DNNs using a completely new approach. We provide a comprehensive IP analysis of large-scale CNNs, investigating the different training phases and providing new insights into the training dynamics of large-scale neural networks.

Discriminative multimodal learning via conditional priors in generative models.

Deep generative models with latent variables have been used lately to learn joint representations and generative processes from multi-modal data, which depict an object from different viewpoints. These two learning mechanisms can, however, conflict with each other and representations can fail to embed information on the data modalities. This research studies the realistic scenario in which all modalities and class labels are available for model training, e.g. images or handwriting, but where some modalities and labels required for downstream tasks are missing, e.g. text or annotations. We show, in this scenario, that the variational lower bound limits mutual information between joint representations and missing modalities. We, to counteract these problems, introduce a novel conditional multi-modal discriminative model that uses an informative prior distribution and optimizes a likelihood-free objective function that maximizes mutual information between joint representations and missing modalities. Extensive experimentation demonstrates the benefits of our proposed model, empirical results show that our model achieves state-of-the-art results in representative problems such as downstream classification, acoustic inversion, and image and annotation generation.

Deep-learning-derived input function in dynamic [18F]FDG PET imaging of mice.

Dynamic positron emission tomography and kinetic modeling play a critical role in tracer development research using small animals. Kinetic modeling from dynamic PET imaging requires accurate knowledge of an input function, ideally determined through arterial blood sampling. Arterial cannulation in mice, however, requires complex, time-consuming and terminal surgery, meaning that longitudinal studies are impossible. The aim of the current work was to develop and evaluate a non-invasive, deep-learning-based prediction model (DLIF) that directly takes the PET data as input to predict a usable input function. We first trained and evaluated the DLIF model on 68 [18F]Fluorodeoxyglucose mouse scans with image-derived targets using cross validation. Subsequently, we evaluated the performance of a trained DLIF model on an external dataset consisting of 8 mouse scans where the input function was measured by continuous arterial blood sampling. The results showed that the predicted DLIF and image-derived targets were similar, and the net influx rate constants following from Patlak modeling using DLIF as input function were strongly correlated to the corresponding values obtained using the image-derived input function. There were somewhat larger discrepancies when evaluating the model on the external dataset, which could be attributed to systematic differences in the experimental setup between the two datasets. In conclusion, our non-invasive DLIF prediction method may be a viable alternative to arterial blood sampling in small animal [18F]FDG imaging. With further validation, DLIF could overcome the need for arterial cannulation and allow fully quantitative and longitudinal experiments in PET imaging studies of mice.

Federated Partially Supervised Learning With Limited Decentralized Medical Images.

Data government has played an instrumental role in securing the privacy-critical infrastructure in the medical domain and has led to an increased need of federated learning (FL). While decentralization can limit the effectiveness of standard supervised learning, the impact of decentralization on partially supervised learning remains unclear. Besides, due to data scarcity, each client may have access to only limited partially labeled data. As a remedy, this work formulates and discusses a new learning problem federated partially supervised learning (FPSL) for limited decentralized medical images with partial labels. We study the impact of decentralized partially labeled data on deep learning-based models via an exemplar of FPSL, namely, federated partially supervised learning multi-label classification. By dissecting FedAVG, a seminal FL framework, we formulate and analyze two major challenges of FPSL and propose a simple yet robust FPSL framework, FedPSL, which addresses these challenges. In particular, FedPSL contains two modules, task-dependent model aggregation and task-agnostic decoupling learning, where the first module addresses the weight assignment and the second module improves the generalization ability of the feature extractor. We provide a comprehensive empirical understanding of FSPL under data scarcity with simulated experiments. The empirical results not only indicate that FPSL is an under-explored problem with practical value but also show that the proposed FedPSL can achieve robust performance against baseline methods on data challenges such as data scarcity and domain shifts. The findings of this study also pose a new research direction towards label-efficient learning on medical images.

ADNet++: A few-shot learning framework for multi-class medical image volume segmentation with uncertainty-guided feature refinement.

A major barrier to applying deep segmentation models in the medical domain is their typical data-hungry nature, requiring experts to collect and label large amounts of data for training. As a reaction, prototypical few-shot segmentation (FSS) models have recently gained traction as data-efficient alternatives. Nevertheless, despite the recent progress of these models, they still have some essential shortcomings that must be addressed. In this work, we focus on three of these shortcomings: (i) the lack of uncertainty estimation, (ii) the lack of a guiding mechanism to help locate edges and encourage spatial consistency in the segmentation maps, and (iii) the models' inability to do one-step multi-class segmentation. Without modifying or requiring a specific backbone architecture, we propose a modified prototype extraction module that facilitates the computation of uncertainty maps in prototypical FSS models, and show that the resulting maps are useful indicators of the model uncertainty. To improve the segmentation around boundaries and to encourage spatial consistency, we propose a novel feature refinement module that leverages structural information in the input space to help guide the segmentation in the feature space. Furthermore, we demonstrate how uncertainty maps can be used to automatically guide this feature refinement. Finally, to avoid ambiguous voxel predictions that occur when images are segmented class-by-class, we propose a procedure to perform one-step multi-class FSS. The efficiency of our proposed methodology is evaluated on two representative datasets for abdominal organ segmentation (CHAOS dataset and BTCV dataset) and one dataset for cardiac segmentation (MS-CMRSeg dataset). The results show that our proposed methodology significantly (one-sided Wilcoxon signed rank test, p<0.05) improves the baseline, increasing the overall dice score with +5.2, +5.1, and +2.8 percentage points for the CHAOS dataset, the BTCV dataset, and the MS-CMRSeg dataset, respectively.

A clinically motivated self-supervised approach for content-based image retrieval of CT liver images.

Deep learning-based approaches for content-based image retrieval (CBIR) of computed tomography (CT) liver images is an active field of research, but suffer from some critical limitations. First, they are heavily reliant on labeled data, which can be challenging and costly to acquire. Second, they lack transparency and explainability, which limits the trustworthiness of deep CBIR systems. We address these limitations by: (1) Proposing a self-supervised learning framework that incorporates domain-knowledge into the training procedure, and, (2) by providing the first representation learning explainability analysis in the context of CBIR of CT liver images. Results demonstrate improved performance compared to the standard self-supervised approach across several metrics, as well as improved generalization across datasets. Further, we conduct the first representation learning explainability analysis in the context of CBIR, which reveals new insights into the feature extraction process. Lastly, we perform a case study with cross-examination CBIR that demonstrates the usability of our proposed framework. We believe that our proposed framework could play a vital role in creating trustworthy deep CBIR systems that can successfully take advantage of unlabeled data.

Anomaly detection-inspired few-shot medical image segmentation through self-supervision with supervoxels.

Recent work has shown that label-efficient few-shot learning through self-supervision can achieve promising medical image segmentation results. However, few-shot segmentation models typically rely on prototype representations of the semantic classes, resulting in a loss of local information that can degrade performance. This is particularly problematic for the typically large and highly heterogeneous background class in medical image segmentation problems. Previous works have attempted to address this issue by learning additional prototypes for each class, but since the prototypes are based on a limited number of slices, we argue that this ad-hoc solution is insufficient to capture the background properties. Motivated by this, and the observation that the foreground class (e.g., one organ) is relatively homogeneous, we propose a novel anomaly detection-inspired approach to few-shot medical image segmentation in which we refrain from modeling the background explicitly. Instead, we rely solely on a single foreground prototype to compute anomaly scores for all query pixels. The segmentation is then performed by thresholding these anomaly scores using a learned threshold. Assisted by a novel self-supervision task that exploits the 3D structure of medical images through supervoxels, our proposed anomaly detection-inspired few-shot medical image segmentation model outperforms previous state-of-the-art approaches on two representative MRI datasets for the tasks of abdominal organ segmentation and cardiac segmentation.

Code-Aligned Autoencoders for Unsupervised Change Detection in Multimodal Remote Sensing Images.

Image translation with convolutional autoencoders has recently been used as an approach to multimodal change detection (CD) in bitemporal satellite images. A main challenge is the alignment of the code spaces by reducing the contribution of change pixels to the learning of the translation function. Many existing approaches train the networks by exploiting supervised information of the change areas, which, however, is not always available. We propose to extract relational pixel information captured by domain-specific affinity matrices at the input and use this to enforce alignment of the code spaces and reduce the impact of change pixels on the learning objective. A change prior is derived in an unsupervised fashion from pixel pair affinities that are comparable across domains. To achieve code space alignment, we enforce pixels with similar affinity relations in the input domains to be correlated also in code space. We demonstrate the utility of this procedure in combination with cycle consistency. The proposed approach is compared with the state-of-the-art machine learning and deep learning algorithms. Experiments conducted on four real and representative datasets show the effectiveness of our methodology.

Uncertainty-Aware Deep Ensembles for Reliable and Explainable Predictions of Clinical Time Series.

Deep learning-based support systems have demonstrated encouraging results in numerous clinical applications involving the processing of time series data. While such systems often are very accurate, they have no inherent mechanism for explaining what influenced the predictions, which is critical for clinical tasks. However, existing explainability techniques lack an important component for trustworthy and reliable decision support, namely a notion of uncertainty. In this paper, we address this lack of uncertainty by proposing a deep ensemble approach where a collection of DNNs are trained independently. A measure of uncertainty in the relevance scores is computed by taking the standard deviation across the relevance scores produced by each model in the ensemble, which in turn is used to make the explanations more reliable. The class activation mapping method is used to assign a relevance score for each time step in the time series. Results demonstrate that the proposed ensemble is more accurate in locating relevant time steps and is more consistent across random initializations, thus making the model more trustworthy. The proposed methodology paves the way for constructing trustworthy and dependable support systems for processing clinical time series for healthcare related tasks.

Uncertainty and interpretability in convolutional neural networks for semantic segmentation of colorectal polyps.

Colorectal polyps are known to be potential precursors to colorectal cancer, which is one of the leading causes of cancer-related deaths on a global scale. Early detection and prevention of colorectal cancer is primarily enabled through manual screenings, where the intestines of a patient is visually examined. Such a procedure can be challenging and exhausting for the person performing the screening. This has resulted in numerous studies on designing automatic systems aimed at supporting physicians during the examination. Recently, such automatic systems have seen a significant improvement as a result of an increasing amount of publicly available colorectal imagery and advances in deep learning research for object image recognition. Specifically, decision support systems based on Convolutional Neural Networks (CNNs) have demonstrated state-of-the-art performance on both detection and segmentation of colorectal polyps. However, CNN-based models need to not only be precise in order to be helpful in a medical context. In addition, interpretability and uncertainty in predictions must be well understood. In this paper, we develop and evaluate recent advances in uncertainty estimation and model interpretability in the context of semantic segmentation of polyps from colonoscopy images. Furthermore, we propose a novel method for estimating the uncertainty associated with important features in the input and demonstrate how interpretability and uncertainty can be modeled in DSSs for semantic segmentation of colorectal polyps. Results indicate that deep models are utilizing the shape and edge information of polyps to make their prediction. Moreover, inaccurate predictions show a higher degree of uncertainty compared to precise predictions.

Explaining decisions of deep neural networks used for fish age prediction.

Age-reading of fish otoliths (ear stones) is important for the sustainable management of fish resources. However, the procedure is challenging and requires experienced readers to carefully examine annual growth zones. In a recent study, convolutional neural networks (CNNs) have been demonstrated to perform reasonably well on automatically predicting fish age from otolith images. In the present study, we carefully investigate the prediction rule learned by such neural networks to provide insight into the features that identify certain fish age ranges. For this purpose, a recent technique for visualizing and analyzing the predictions of the neural networks was applied to different versions of the otolith images. The results indicate that supplementary knowledge about the internal structure improves the results for the youngest age groups, compared to using only the contour shape attribute of the otolith. However, the contour shape and size attributes are, in general, sufficient for older age groups. In addition, within specific age ranges we find that the network tends to focus on particular areas of the otoliths and that the most discriminating factors seem to be related to the central part and the outer edge of the otolith. Explaining age predictions from otolith images as done in this study will hopefully help build confidence in the potential of deep learning algorithms for automatic age prediction, as well as improve the quality of the age estimation.

Deep divergence-based approach to clustering.

A promising direction in deep learning research consists in learning representations and simultaneously discovering cluster structure in unlabeled data by optimizing a discriminative loss function. As opposed to supervised deep learning, this line of research is in its infancy, and how to design and optimize suitable loss functions to train deep neural networks for clustering is still an open question. Our contribution to this emerging field is a new deep clustering network that leverages the discriminative power of information-theoretic divergence measures, which have been shown to be effective in traditional clustering. We propose a novel loss function that incorporates geometric regularization constraints, thus avoiding degenerate structures of the resulting clustering partition. Experiments on synthetic benchmarks and real datasets show that the proposed network achieves competitive performance with respect to other state-of-the-art methods, scales well to large datasets, and does not require pre-training steps.

ConnNet: A Long-Range Relation-Aware Pixel-Connectivity Network for Salient Segmentation.

Salient segmentation aims to segment out attentiongrabbing regions, a critical yet challenging task and the foundation of many high-level computer vision applications. It requires semantic-aware grouping of pixels into salient regions and benefits from the utilization of global multi-scale contexts to achieve good local reasoning. Previous works often address it as two-class segmentation problems utilizing complicated multi-step procedures including refinement networks and complex graphical models. We argue that semantic salient segmentation can instead be effectively resolved by reformulating it as a simple yet intuitive pixel-pair based connectivity prediction task. Following the intuition that salient objects can be naturally grouped via semanticaware connectivity between neighboring pixels, we propose a pure Connectivity Net (ConnNet). ConnNet predicts connectivity probabilities of each pixel with its neighboring pixels by leveraging multi-level cascade contexts embedded in the image and long-range pixel relations. We investigate our approach on two tasks, namely salient object segmentation and salient instancelevel segmentation, and illustrate that consistent improvements can be obtained by modeling these tasks as connectivity instead of binary segmentation tasks for a variety of network architectures. We achieve state-of-the-art performance, outperforming or being comparable to existing approaches while reducing inference time due to our less complex approach.