Recent advances in computational and algorithmic power are evolving the field of medical imaging rapidly. In cancer research, many new directions are sought to characterize patients with additional imaging features derived from radiology and pathology images. The emerging field of Computational Pathology targets the high-throughput extraction and analysis of the spatial distribution of cells from digital histopathology images. The associated morphological and architectural features allow researchers to quantify and characterize new imaging biomarkers for cancer diagnosis, prognosis, and treatment decisions. However, while the image feature space grows, exploration and analysis become more difficult and ineffective. There is a need for dedicated interfaces for interactive data manipulation and visual analysis of computational pathology and clinical data. For this purpose, we present IIComPath, a visual analytics approach that enables clinical researchers to formulate hypotheses and create computational pathology pipelines involving cohort construction, spatial analysis of image-derived features, and cohort analysis. We demonstrate our approach through use cases that investigate the prognostic value of current diagnostic features and new computational pathology biomarkers.

Abstract The usage of deep learning models for tagging input data has increased over the past years because of their accuracy and high‐performance. A successful application is to score sleep stages. In this scenario, models are trained to predict the sleep stages of individuals. Although their predictive accuracy is high, there are still mis classifications that prevent doctors from properly diagnosing sleep‐related disorders. This paper presents a system that allows users to explore the output of deep learning models in a real‐life scenario to spot and analyze faulty predictions. These can be corrected by users to generate a sequence of sleep stages to be examined by doctors. Our approach addresses a real‐life scenario with absence of ground truth. It differs from others in that our goal is not to improve the model itself, but to correct the predictions it provides. We demonstrate that our approach is effective in identifying faulty predictions and helping users to fix them in the proposed use case.

Abstract Process mining enables organizations to analyze data about their (business) processes. Visualization is key to gaining insight into these processes and the associated data. Process visualization requires a high‐quality graph layout that intuitively represents the semantics of the process. Process analysis additionally requires interactive filtering to explore the process data and process graph. The ideal process visualization therefore provides a high‐quality, intuitive layout and preserves the mental map of the user during the visual exploration. The current industry standard used for process visualization does not satisfy either of these requirements. In this paper, we propose a novel layout algorithm for processes based on the Sugiyama framework. Our approach consists of novel ranking and order constraint algorithms and a novel crossing minimization algorithm. These algorithms make use of the process data to compute stable, high‐quality layouts. In addition, we use phased animation to further improve mental map preservation. Quantitative and qualitative evaluations show that our approach computes layouts of higher quality and preserves the mental map better than the industry standard. Additionally, our approach is substantially faster, especially for graphs with more than 250 edges.

We propose a novel type of low distortion radial embedding which focuses on one specific entity and its closest neighbors. Our embedding preserves near-exact distances to the focus entity and aims to minimize distortion between the other entities. We present an interactive exploration tool SolarView which places the focus entity at the center of a "solar system" and embeds its neighbors guided by concentric circles. SolarView provides an implementation of our novel embedding and several state-of-the-art dimensionality reduction and embedding techniques, which we adapted to our setting in various ways. We experimentally evaluated our embedding and compared it to these state-of-the-art techniques. The results show that our embedding competes with these techniques and achieves low distortion in practice. Our method performs particularly well when the visualization, and hence the embedding, adheres to the solar system design principle of our application. Nonetheless-as with all dimensionality reduction techniques-the distortion may be high. We leverage interaction techniques to give clear visual cues that allow users to accurately judge distortion. We illustrate the use of SolarView by exploring the high-dimensional metric space of bibliographic entity similarities.

The analysis of interaction between movement trajectories is of interest for various domains when movement of multiple objects is concerned. Interaction often includes a delayed response, making it difficult to detect interaction with current methods that compare movement at specific time intervals. We propose analyses and visualizations, on a local and global scale, of delayed movement responses, where an action is followed by a reaction over time, on trajectories recorded simultaneously. We developed a novel approach to compute the global delay in subquadratic time using a fast Fourier transform (FFT). Central to our local analysis of delays is the computation of a matching between the trajectories in a so-called delay space. It encodes the similarities between all pairs of points of the trajectories. In the visualization, the edges of the matching are bundled into patches, such that shape and color of a patch help to encode changes in an interaction pattern. To evaluate our approach experimentally, we have implemented it as a prototype visual analytics tool and have applied the tool on three bidimensional data sets. For this we used various measures to compute the delay space, including the directional distance, a new similarity measure, which captures more complex interactions by combining directional and spatial characteristics. We compare matchings of various methods computing similarity between trajectories. We also compare various procedures to compute the matching in the delay space, specifically the Fréchet distance, dynamic time warping (DTW), and edit distance (ED). Finally, we demonstrate how to validate the consistency of pairwise matchings by computing matchings between more than two trajectories.

Interactions between trajectories need to be analyzed in various domains to gain insight into movement patterns. Such interactions often take place with some delayed response. We propose an approach to analyze and visualize delayed responses on two trajectories recorded simultaneously and with the same sampling rate. Central to our approach is the computation of a matching between the trajectories in a so-called delay space. We also introduce a new similarity measure between trajectories, which combines directional and spatial characteristics. To evaluate our approach experimentally, we have implemented it as a prototype visual analytics tool and have applied the tool on two datasets.

Abstract Node grouping is a common way of adding structure and information to networks that aids their interpretation. However, certain networks benefit from the grouping of links instead of nodes. Link communities, for example, are a form of link groups that describe high‐quality overlapping node communities. There is a conceptual gap between node groups and link groups that poses an interesting visualization challenge. We introduce the Dual Adjacency Matrix to bridge this gap. This matrix combines node and link group techniques via a generalization that also enables it to be coordinated with a node‐link‐contour diagram. These methods have been implemented in a prototype that we evaluated with an information scientist and neuroscientist via interviews and prototype walk‐throughs. We demonstrate this prototype with the analysis of a trade network and an fMRI correlation network.

Magnetic resonance diffusion tensor imaging (DTI) measures diffusion of water molecules and is used to characterize orientation of white matter fibers and connectivity of neurological structures. Segmentation and visualization of DT images is challenging, because of low data quality and complexity of anatomical structures. In this paper, we propose an interactive segmentation approach, based on a hierarchical representation of the input DT image through a tree structure. The tree is obtained by successively merging watershed regions, based on the morphological waterfall approach, hence the name watershed tree. Region merging is done according to a combined similarity and homogeneity criterion. We introduce filters that work on the proposed tree representation, and that enable region-based attribute filtering of DTI data. Linked views between the visualizations of the simplified DT image and the tree enable a user to visually explore both data and tree at interactive rates. The coupling of filtering, semiautomatic segmentation by labeling nodes in the tree, and various interaction mechanisms support the segmentation task. Our method is robust against noise, which we demonstrate on synthetic and real DTI data.

Progressive algorithms are algorithms that, on the way to computing a complete solution to the problem at hand, output intermediate solutions that approximate the complete solution increasingly well. We present a framework for analyzing such algorithms, and develop efficient progressive algorithms for two geometric problems: computing the convex hull of a planar point set, and finding popular places in a set of trajectories.

We present an algorithmic framework for criteria-based segmentation of trajectories that can efficiently process a large class of criteria. Criteria-based segmentation is the problem of subdividing a trajectory into a small number of parts such that each part satisfies a global criterion. Our framework can handle criteria that are stable, in the sense that these do not change their validity along the trajectory very often. This includes both increasing and decreasing monotone criteria. Our framework takes O(n log n) time for preprocessing and computation, where n is the number of data points. It surpasses the two previous algorithmic frameworks on criteria-based segmentation, which could only handle decreasing monotone criteria, or had a quadratic running time, respectively. Furthermore, we develop an efficient data structure for interactive parameter selection, and provide mechanisms to improve the exact position of break points in the segmentation. We demonstrate and evaluate our framework by performing case studies on real-world data sets.

BACKGROUND: Biological networks have a growing importance for the interpretation of high-throughput "omics" data. Integrative network analysis makes use of statistical and combinatorial methods to extract smaller subnetwork modules, and performs enrichment analysis to annotate the modules with ontology terms or other available knowledge. This process results in an annotated module, which retains the original network structure and includes enrichment information as a set system. A major bottleneck is a lack of tools that allow exploring both network structure of extracted modules and its annotations. RESULTS: This paper presents a visual analysis approach that targets small modules with many set-based annotations, and which displays the annotations as contours on top of a node-link diagram. We introduce an extension of self-organizing maps to lay out nodes, links, and contours in a unified way. An implementation of this approach is freely available as the Cytoscape app eXamine CONCLUSIONS: eXamine accurately conveys small and annotated modules consisting of several dozens of proteins and annotations. We demonstrate that eXamine facilitates the interpretation of integrative network analysis results in a guided case study. This study has resulted in a novel biological insight regarding the virally-encoded G-protein coupled receptor US28.

Abstract We present Kelp Diagrams, a novel method to depict set relations over points, i.e., elements with predefined positions. Our method creates schematic drawings and has been designed to take aesthetic quality, efficiency, and effectiveness into account. This is achieved by a routing algorithm, which links elements that are part of the same set by constructing minimum cost paths over a tangent visibility graph. There are two styles of Kelp Diagrams to depict overlapping sets, a nested and a striped style, each with its own strengths and weaknesses. We compare Kelp Diagrams with two existing methods and show that our approach provides a more consistent and clear depiction of both element locations and their set relations.

We present a novel technique-Compressed Adjacency Matrices-for visualizing gene regulatory networks. These directed networks have strong structural characteristics: out-degrees with a scale-free distribution, in-degrees bound by a low maximum, and few and small cycles. Standard visualization techniques, such as node-link diagrams and adjacency matrices, are impeded by these network characteristics. The scale-free distribution of out-degrees causes a high number of intersecting edges in node-link diagrams. Adjacency matrices become space-inefficient due to the low in-degrees and the resulting sparse network. Compressed adjacency matrices, however, exploit these structural characteristics. By cutting open and rearranging an adjacency matrix, we achieve a compact and neatly-arranged visualization. Compressed adjacency matrices allow for easy detection of subnetworks with a specific structure, so-called motifs, which provide important knowledge about gene regulatory networks to domain experts. We summarize motifs commonly referred to in the literature, and relate them to network analysis tasks common to the visualization domain. We show that a user can easily find the important motifs in compressed adjacency matrices, and that this is hard in standard adjacency matrix and node-link diagrams. We also demonstrate that interaction techniques for standard adjacency matrices can be used for our compressed variant. These techniques include rearrangement clustering, highlighting, and filtering.

Abstract We propose visual analytics techniques to support concurrent comparison of hundreds of cumulatively weighted instances of a single hierarchy. This includes a node‐link representation of the hierarchy where nodes depict the weights of all instances with high‐density heat maps that are grouped and aligned to ease cross‐referencing. Hierarchy exploration is facilitated by smoothly animated expansion and collapse of its branches. Detailed information about hierarchy structure, weights, and meta‐data is provided by secondary linked visualizations. These techniques have been implemented in a prototype tool, in which the computational analysis concerns have been strictly separated from the visualization concerns. The analysis algorithms are extensible via a script engine. We discuss the effectiveness of our techniques for the visual analytic process of microbe community profiling experts.

Abstract Summary: SpotXplore is a plugin for Cytoscape for extraction and visualization of differentially expressed subnetworks (hotspots) from gene networks. The hotspot-based visualization approach enables interactive exploration of regulatory interactions in differentially expressed gene sets, and it allows a researcher to explore gene expression in direct relation to the affected cellular gene network. The hotspots provide a view beyond the commonly used metabolic pathways and gene ontologies. Availability: http://www.win.tue.nl/∼mwestenb/spotxplore/ Contact: [email protected] Supplementary information: Example data and user manual are available at SpotXplore's web site.

We present an application for integrated visualization of gene expression data from time series experiments in gene regulation networks and metabolic networks. Such integration is necessary, since it provides the link between the measurements at the transcriptional level and the observable characteristics of an organism at the functional level. Our application can (i) visualize the data from time series experiments in the context of a regulatory network and a metabolic network; (ii) identify and visualize active regulatory subnetworks from the gene expression data; (iii) perform a statistical test to identify and subsequently visualize affected metabolic subnetworks. Initial results show that our integrated approach speeds up data analysis, and that it can reproduce results of a traditional approach that involves many manual and time-consuming steps.

Abstract DNA microarrays are used to measure the expression levels of thousands of genes simultaneously. In a time series experiment, the gene expressions are measured as a function of time. We present an application for integrated visualization of genome expression and network dynamics in both regulatory networks and metabolic pathways. Integration of these two levels of cellular processes is necessary, since it provides the link between the measurements at the transcriptional level (gene expression levels approximated from microarray data) and the phenotype (the observable characteristics of an organism) at the functional and behavioral level. The integration requires visualization approaches besides traditional clustering and statistical analysis methods. Our application can (i) visualize the data from time series experiments in the context of a regulatory network and KEGG metabolic pathways; (ii) identify and visualize active regulatory subnetworks from the gene expression data; (iii) perform a statistical test to identify and subsequently visualize pathways that are affected by differentially expressed genes. We present a case study, which demonstrates that our approach and application both facilitates and speeds up data analysis tremendously in comparison to a more traditional approach that involves many manual, laborious, and error‐prone steps.

The Max-Tree designed for morphological attribute filtering in image processing, is a data structure in which the nodes represent connected components for all threshold levels in a data set. Attribute filters compute some attribute describing the shape or size of each connected component and then decide which components to keep or to discard. In this paper, we augment the basic Max-Tree data structure such that interactive volumetric filtering and visualization becomes possible. We introduce extensions that allow (1) direct, splatting-based, volume rendering; (2) representation of the Max-Tree on graphics hardware; and (3) fast active cell selection for isosurface generation. In all three cases, we can use the Max-Tree representation for visualization directly, without needing to reconstruct the volumetric data explicitly. We show that both filtering and visualization can be performed at interactive frame rates, ranging between 2.4 and 32 frames per seconds. In contrast, a standard texture-based volume visualization method manages only between 0.5 and 1.8 frames per second. For isovalue browsing, the experimental results show that the performance is comparable to the performance of an interval tree, where our method has the advantage that both filter threshold browsing and isolevel browsing are fast. It is shown that the methods using graphics hardware can be extended to other connected filters.

Noise reduction is an important preprocessing step for many visualization techniques that make use of feature extraction. We propose a method for denoising 2-D vector fields that are corrupted by additive noise. The method is based on the vector wavelet transform and wavelet coefficient thresholding. We compare our wavelet-based denoising method with Gaussian filtering, and test the effect of these methods on the signal-to-noise ratio (SNR) of the vector fields before and after denoising. We also study the effect on relevant details for visualization, such as vortex measures. The results show that for low SNR, Gaussian filtering with large kernels has a somewhat higher performance than the wavelet-based method in terms of SNR. For larger SNR, the wavelet-based method outperforms Gaussian filtering. This is mostly due to the fact that Gaussian filtering tends to remove small details, which are preserved by the wavelet-based method.

We propose a biologically motivated computational step, called non-classical receptive field (non-CRF) inhibition, to improve contour detection in images of natural scenes. We augment a Gabor energy operator with non-CRF inhibition. The resulting contour operator responds strongly to isolated lines, edges, and contours but exhibits a weaker or no response to edges that make part of texture. As such, the contour operator is more useful for contour-based object recognition tasks than traditional edge detectors, which do not make such a distinction. The contour operator consistently outperforms the Canny edge detector on natural images with associated ground truth contour maps.

Two moving-window methods, using either flat or Gaussian weighted windows, for local thresholding with robust automatic threshold selection are developed. The results show that fast segmentation of blood vessels against a varying background and noise is possible at modest computational cost. Volumes of 128 x 256/sup 2/ and 256/sup 3/ can be segmented in 3.1 s and 6.6 s, for flat, and 12.6 s and 30.8 s for Gaussian windows, respectively, on a 1.9 GHz Pentium 4.

We propose a biologically motivated method, called nonclassical receptive field (non-CRF) inhibition (more generally, surround inhibition or suppression), to improve contour detection in machine vision. Non-CRF inhibition is exhibited by 80% of the orientation-selective neurons in the primary visual cortex of monkeys and has been shown to influence human visual perception as well. Essentially, the response of an edge detector at a certain point is suppressed by the responses of the operator in the region outside the supported area. We combine classical edge detection with isotropic and anisotropic inhibition, both of which have counterparts in biology. We also use a biologically motivated method (the Gabor energy operator) for edge detection. The resulting operator responds strongly to isolated lines, edges, and contours, but exhibits weak or no response to edges that are part of texture. We use natural images with associated ground truth contour maps to assess the performance of the proposed operator for detecting contours while suppressing texture edges. Our method enhances contour detection in cluttered visual scenes more effectively than classical edge detectors used in machine vision (Canny edge detector). Therefore, the proposed operator is more useful for contour-based object recognition tasks, such as shape comparison, than traditional edge detectors, which do not distinguish between contour and texture edges. Traditional edge detection algorithms can, however, also be extended with surround suppression. This study contributes also to the understanding of inhibitory mechanisms in biology.

This paper is concerned with X-ray volume visualization by means of wavelet splatting, a wavelet-based extension to splatting. Wavelet splatting allows multiresolution visualization of volume data. During user interaction, only low resolution images are computed. When interaction ceases, the image is refined incrementally. We discuss a particular implementation of wavelet splatting which was proposed previously, and show that certain rendering artefacts appear in the low resolution images, due to the particular ordering of the wavelet coefficients. We propose a new variant that uses a different ordering, and computes low resolution images based on the wavelet approximation coefficients only. This variant does not suffer from artefacts, and is faster by a factor of two to three.

We describe a wavelet based X-ray rendering method in the frequency domain with a smaller time complexity than wavelet splatting. Standard Fourier volume rendering is summarized and interpolation and accuracy issues are briefly discussed. We review the implementation of the fast wavelet transform in the frequency domain. The wavelet X-ray transform is derived, and the corresponding Fourier-wavelet volume rendering algorithm (FWVR) is introduced, FWVR uses Haar or B-spline wavelets and linear or cubic spline interpolation. Various combinations are tested and compared with wavelet splatting (WS). We use medical MR and CT scan data, as well as a 3-D analytical phantom to assess the accuracy, time complexity, and memory cost of both FWVR and WS. The differences between both methods are enumerated.