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Retinal lesions caused by eye diseases such as glaucoma and age-related macular degeneration can, over time, eliminate stimulation of parts of the visual cortex. This could lead to degeneration of inactive cortical neuronal tissue, but this has not been established in humans. Here, we used magnetic resonance imaging to assess the effects of prolonged sensory deprivation in human visual cortex. High-resolution anatomical magnetic resonance images were obtained in subjects with foveal (age-related macular degeneration) and peripheral (glaucoma) retinal lesions as well as age-matched controls. Comparison of grey matter between patient and control groups revealed density reductions in the approximate retinal lesion projection zones in visual cortex. This indicates that long-term cortical deprivation, due to retinal lesions acquired later in life, is associated with retinotopic-specific neuronal degeneration of visual cortex. Such degeneration could interfere with therapeutic strategies such as the future application of artificial retinal implants to overcome lesion-induced visual impairment. [ABSTRACT FROM AUTHOR]

Background: Exergames are becoming an increasingly popular tool for training balance ability, thereby preventing falls in older adults. Automatic, real time, assessment of the user's balance control offers opportunities in terms of providing targeted feedback and dynamically adjusting the gameplay to the individual user, yet algorithms for quantification of balance control remain to be developed. The aim of the present study was to identify movement patterns, and variability therein, of young and older adults playing a custom-made weight-shifting (ice-skating) exergame., Methods: Twenty older adults and twenty young adults played a weight-shifting exergame under five conditions of varying complexity, while multi-segmental whole-body movement data were captured using Kinect. Movement coordination patterns expressed during gameplay were identified using Self Organizing Maps (SOM), an artificial neural network, and variability in these patterns was quantified by computing Total Trajectory Variability (TTvar). Additionally a k Nearest Neighbor (kNN) classifier was trained to discriminate between young and older adults based on the SOM features., Results: Results showed that TTvar was significantly higher in older adults than in young adults, when playing the exergame under complex task conditions. The kNN classifier showed a classification accuracy of 65.8%., Conclusions: Older adults display more variable sway behavior than young adults, when playing the exergame under complex task conditions. The SOM features characterizing movement patterns expressed during exergaming allow for discriminating between young and older adults with limited accuracy. Our findings contribute to the development of algorithms for quantification of balance ability during home-based exergaming for balance training.

We present a visualization technique for brain fiber tracts from DTI data that provides insight into the structure of white matter through visual abstraction. We achieve this abstraction by analyzing the local similarity of tract segment directions at different scales using a stepwise increase of the search range. Next, locally similar tract segments are moved toward each other in an iterative process, resulting in a local contraction of tracts perpendicular to the local tract direction at a given scale. This not only leads to the abstraction of the global structure of the white matter as represented by the tracts, but also creates volumetric voids. This increase of empty space decreases the mutual occlusion of tracts and, consequently, results in a better understanding of the brain's three-dimensional fiber tract structure. Our implementation supports an interactive and continuous transition between the original and the abstracted representations via various scale levels of similarity. We also support the selection of groups of tracts, which are highlighted and rendered with the abstracted visualization as context.

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.

Medical imaging techniques like fluorodeoxyglucose positron emission tomography (FDG-PET) have been used to aid in the differential diagnosis of neurodegenerative brain diseases. In this study, the objective is to classify FDG-PET brain scans of subjects with Parkinsonian syndromes (Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy) compared to healthy controls. The scaled subprofile model/principal component analysis (SSM/PCA) method was applied to FDG-PET brain image data to obtain covariance patterns and corresponding subject scores. The latter were used as features for supervised classification by the C4.5 decision tree method. Leave-one-out cross validation was applied to determine classifier performance. We carried out a comparison with other types of classifiers. The big advantage of decision tree classification is that the results are easy to understand by humans. A visual representation of decision trees strongly supports the interpretation process, which is very important in the context of medical diagnosis. Further improvements are suggested based on enlarging the number of the training data, enhancing the decision tree method by bagging, and adding additional features based on (f)MRI data.

Introduction: Under normal conditions, the spatial distribution of resting cerebral blood flow and cerebral metabolic rate of glucose are closely related. A relatively new magnetic resonance (MR) technique, pseudo-continuous arterial spin labeling (PCASL), can be used to measure regional brain perfusion. We identified a Parkinson's disease (PD)-related perfusion and metabolic covariance pattern in the same patients using PCASL and FDG-PET imaging and assessed (dis)similarities in the disease-related pattern between perfusion and metabolism in PD patients., Methods: Nineteen PD patients and seventeen healthy controls underwent [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Of 14 PD patients and all healthy controls PCASL-MRI could be obtained. Data were analyzed using scaled subprofile model/principal component analysis (SSM/PCA)., Results: Unique Parkinson's disease-related perfusion and metabolic covariance patterns were identified using PCASL and FDG-PET in the same patients. The PD-related metabolic covariance brain pattern is in high accordance with previously reports. Also our disease-related perfusion pattern is comparable to the earlier described perfusion pattern. The most marked difference between our perfusion and metabolic patterns is the larger perfusion decrease in cortical regions including the insula., Conclusion: We identified PD-related perfusion and metabolic brain patterns using PCASL and FDG-PET in the same patients which were comparable with results of existing research. In this respect, PCASL appears to be a promising addition in the early diagnosis of individual parkinsonian patients.

Mathematical morphology is a very popular framework for processing binary or grayscale images. One of the key problems in applying this framework to color images is the notorious false color problem. We discuss the nature of this problem and its origins. In doing so, it becomes apparent that the lack of invariance of operators to certain transformations (forming a group) plays an important role. The main culprits are the basic join and meet operations, and the associated lattice structure that forms the theoretical basis for mathematical morphology. We show how a lattice that is not group invariant can be related to another lattice that is. When all transformations in a group are linear, these lattices can be related to one another via the theory of frames. This provides all the machinery to let us transform any (grayscale or color) morphological filter into a group-invariant filter on grayscale or color images. We then demonstrate the potential for both subjective and objective improvement in selected tasks.

Purpose: [(18)F]fluorodeoxyglucose (FDG) PET imaging of the brain can be used to assist in the differential diagnosis of dementia. Group differences in glucose uptake between patients with dementia and controls are well-known. However, a multivariate analysis technique called scaled subprofile model, principal component analysis (SSM/PCA) aiming at identifying diagnostic neural networks in diseases, have been applied less frequently. We validated an Alzheimer's Disease-related (AD) glucose metabolic brain pattern using the SSM/PCA analysis and applied it prospectively in an independent confirmation cohort., Methods: We used FDG-PET scans of 18 healthy controls and 15 AD patients (identification cohort) to identify an AD-related glucose metabolic covariance pattern. In the confirmation cohort (n=15), we investigated the ability to discriminate between probable AD and non-probable AD (possible AD, mild cognitive impairment (MCI) or subjective complaints)., Results: The AD-related metabolic covariance pattern was characterized by relatively decreased metabolism in the temporoparietal regions and relatively increased metabolism in the subcortical white matter, cerebellum and sensorimotor cortex. Receiver-operating characteristic (ROC) curves showed at a cut-off value of z=1.23, a sensitivity of 93% and a specificity of 94% for correct AD classification. In the confirmation cohort, subjects with clinically probable AD diagnosis showed a high expression of the AD-related pattern whereas in subjects with a non-probable AD diagnosis a low expression was found., Conclusion: The Alzheimer's disease-related cerebral glucose metabolic covariance pattern identified by SSM/PCA analysis was highly sensitive and specific for Alzheimer's disease. This method is expected to be helpful in the early diagnosis of Alzheimer's disease in clinical practice.

Background: The objective of this study was to validate disease-related metabolic brain patterns for Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy., Methods: The study included 20 patients with Parkinson's disease, 21 with multiple system atrophy, and 17 with progressive supranuclear palsy, all of whom had undergone a clinically motivated [18F]-fluoro-deoxyglucose positron emission tomography scan at an early stage of their disease. At a follow-up time after the scan of 2-4 years, a clinical diagnosis was made according to established clinical research criteria. Patient groups were compared with 18 healthy controls using a multivariate covariance image analysis technique called scaled subprofile model/principal component analysis., Results: Disease-related metabolic brain patterns for these parkinsonian disorders were identified. Validation showed that these patterns were highly discriminative of the 3 disorders., Conclusions: Early diagnosis of parkinsonian disorders is feasible when the expression of disease-related metabolic brain patterns is quantified at a single-subject level., (Copyright © 2012 Movement Disorder Society.)

The level-set method is one of the most popular techniques for capturing and tracking deformable interfaces. Although level sets have demonstrated great potential in visualization and computer graphics applications, such as surface editing and physically based modeling, their use for interactive simulations has been limited due to the high computational demands involved. In this paper, we address this computational challenge by leveraging the increased computing power of graphics processors, to achieve fast simulations based on level sets. Our efficient, sparse GPU level-set method is substantially faster than other state-of-the-art, parallel approaches on both CPU and GPU hardware. We further investigate its performance through a method for surface reconstruction, based on GPU level sets. Our novel multiresolution method for surface reconstruction from unorganized point clouds compares favorably with recent, existing techniques and other parallel implementations. Finally, we point out that both level-set computations and rendering of level-set surfaces can be performed at interactive rates, even on large volumetric grids. Therefore, many applications based on level sets can benefit from our sparse level-set method.

We propose the use of force-directed graph layout as an explorative tool for connectivity-based brain parcellation studies. The method can be used as a heuristic to find the number of clusters intrinsically present in the data (if any) and to investigate their organisation. It provides an intuitive representation of the structure of the data and facilitates interactive exploration of properties of single seed voxels as well as relations among (groups of) voxels. We validate the method on synthetic data sets and we investigate the changes in connectivity in the supplementary motor cortex, a brain region whose parcellation has been previously investigated via connectivity studies. This region is supposed to present two easily distinguishable connectivity patterns, putatively denoted by SMA (supplementary motor area) and pre-SMA. Our method provides insights with respect to the connectivity patterns of the premotor cortex. These present a substantial variation among subjects, and their subdivision into two well-separated clusters is not always straightforward., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We have determined the time-resolved transcriptome of the model gram-positive organism B. subtilis during growth in a batch fermentor on rich medium. DNA microarrays were used to monitor gene transcription using 10-minute intervals at 40 consecutive time points. From the growth curve and analysis of all gene expression levels, we identified 4 distinct growth phases and one clear transition point: a lag phase, an exponential growth phase, the transition point and the very clearly separated early and late stationary growth phases. The gene expression profiles suggest the occurrence of stress responses at specific times although no external stresses were applied. The first one is a small induction of the SigB regulon that occurs at the transition point. Remarkably, a very strong response is observed for the SigW regulon, which is highly upregulated at the onset of the late stationary phase. Bioinformatic analyses that were performed on our data set suggest several novel putative motifs for regulator binding. In addition, the expression profiles of several genes appeared to correlate with the oxygen concentration. This data set of the expression profiles of all B. subtilis genes during the entire growth curve on rich medium constitutes a rich repository that can be further mined by the scientific community.

Unlabelled: 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/.

Tinnitus is an auditory percept in the absence of an external sound source. Mechanisms in the central nervous system are believed to be key in the pathophysiology of tinnitus. Diffusion tensor imaging (DTI) is an MR imaging technique that allows in vivo exploration of white matter tissue in the human brain. Using a probabilistic DTI approach, we determined the characteristics of fiber tracts from the inferior colliculus to the medial geniculate body up to the primary auditory cortex. We also investigated the connections between the auditory system and the amygdala, which may be involved in some forms of tinnitus. White matter tracts were characterized by three quantities: the mean fractional anisotropy, the weighted mean fractional anisotropy and the path strength. All these quantities are measures of the patency of white matter tracts. The most important finding is an increased patency of the white matter tracts between the auditory cortex and the amygdala in tinnitus patients as compared to healthy controls.

An object in the peripheral visual field is more difficult to recognize when surrounded by other objects. This phenomenon is called "crowding". Crowding places a fundamental constraint on human vision that limits performance on numerous tasks. It has been suggested that crowding results from spatial feature integration necessary for object recognition. However, in the absence of convincing models, this theory has remained controversial. Here, we present a quantitative and physiologically plausible model for spatial integration of orientation signals, based on the principles of population coding. Using simulations, we demonstrate that this model coherently accounts for fundamental properties of crowding, including critical spacing, "compulsory averaging", and a foveal-peripheral anisotropy. Moreover, we show that the model predicts increased responses to correlated visual stimuli. Altogether, these results suggest that crowding has little immediate bearing on object recognition but is a by-product of a general, elementary integration mechanism in early vision aimed at improving signal quality.

We present a technique for the illustrative rendering of 3D line data at interactive frame rates. We create depth-dependent halos around lines to emphasize tight line bundles while less structured lines are de-emphasized. Moreover, the depth-dependent halos combined with depth cueing via line width attenuation increase depth perception, extending techniques from sparse line rendering to the illustrative visualization of dense line data. We demonstrate how the technique can be used, in particular, for illustrating DTI fiber tracts but also show examples from gas and fluid flow simulations and mathematics as well as describe how the technique extends to point data. We report on an informal evaluation of the illustrative DTI fiber tract visualizations with domain experts in neurosurgery and tractography who commented positively about the results and suggested a number of directions for future work.

The purpose of the present study is to examine the effects of mental fatigue and motivation on neural network dynamics activated during task switching. Mental fatigue was induced by 2 h of continuous performance; after which subjects were motivated by using social comparison and monetary reward as motivating factors to perform well for an additional 20 min. EEG coherence was used as a measure of synchronization of brain activity. Electrodes of interest were identified using a data-driven pre-processing method (ten Caat, M., Lorist, M.M., Bezdan, E., Roerdink, J.B.T.M., Maurits, N.M., 2008a. High-density EEG coherence analysis using functional units applied to mental fatigue. J. Neurosci. Meth. 171, 271-278; ten Caat, M., Maurits, N.M. and Roerdink, J.B.T.M., 2008b. Data-driven visualization and group analysis of multichannel EEG coherence with functional units. IEEE T. Vis. Comp. Gr. 14, 756-771). Performance on repetition trials was faster and more accurate than on switch trials. EEG data revealed more pronounced, frequency specific fronto-parietal network activation in switch trials, while power density was higher in repetition trials. The effects of mental fatigue on power and coherence were widespread, and not limited to specific frequency bands. Moreover, these effects were independent of specific task manipulations. This increase in neuronal activity and stronger synchronization between neural networks did not result in more efficient performance; response speed decreased and the number of errors increased in fatigued subjects. A modulation of the dopamine system is proposed as a common mechanism underlying the observed the fatigue effects.

A physically motivated method for surface reconstruction is proposed that can recover smooth surfaces from noisy and sparse data sets. No orientation information is required. By a new technique based on regularized-membrane potentials the input sample points are aggregated, leading to improved noise tolerability and outlier removal, without sacrificing much with respect to detail (feature) recovery. After aggregating the sample points on a volumetric grid, a novel, iterative algorithm is used to classify grid points as exterior or interior to the surface. This algorithm relies on intrinsic properties of the smooth scalar field on the grid which emerges after the aggregation step. Second, a mesh-smoothing paradigm based on a mass-spring system is introduced. By enhancing this system with a bending-energy minimizing term we ensure that the final triangulated surface is smoother than piecewise linear. In terms of speed and flexibility, the method compares favorably with respect to previous approaches. Most parts of the method are implemented on modern graphics processing units (GPUs). Results in a wide variety of settings are presented, ranging from surface reconstruction on noise-free point clouds to grayscale image segmentation.

Visual information is difficult to search and interpret when the density of the displayed information is high or the layout is chaotic. Visual information that exhibits such properties is generally referred to as being "cluttered." Clutter should be avoided in information visualizations and interface design in general because it can severely degrade task performance. Although previous studies have identified computable correlates of clutter (such as local feature variance and edge density), understanding of why humans perceive some scenes as being more cluttered than others remains limited. Here, we explore an account of clutter that is inspired by findings from visual perception studies. Specifically, we test the hypothesis that the so-called "crowding" phenomenon is an important constituent of clutter. We constructed an algorithm to predict visual clutter in arbitrary images by estimating the perceptual impairment due to crowding. After verifying that this model can reproduce crowding data we tested whether it can also predict clutter. We found that its predictions correlate well with both subjective clutter assessments and search performance in cluttered scenes. These results suggest that crowding and clutter may indeed be closely related concepts and suggest avenues for further research.

Summary: Unraveling regulatory mechanisms (e.g. identification of motifs in cis-regulatory regions) remains a major challenge in the analysis of transcriptome experiments. Existing applications identify putative motifs from gene lists obtained at rather arbitrary cutoff and require additional manual processing steps. Our standalone application MOTIFATOR identifies the most optimal parameters for motif discovery and creates an interactive visualization of the results. Discovered putative motifs are functionally characterized, thereby providing valuable insight in the biological processes that could be controlled by the motif., Availability: MOTIFATOR is freely available at http://www.motifator.nl.

Background: A typical step in the analysis of gene expression data is the determination of clusters of genes that exhibit similar expression patterns. Researchers are confronted with the seemingly arbitrary choice between numerous algorithms to perform cluster analysis., Results: We developed an exploratory application that benchmarks the results of clustering methods using functional annotations. In addition, a de novo DNA motif discovery algorithm is integrated in our program which identifies overrepresented DNA binding sites in the upstream DNA sequences of genes from the clusters that are indicative of sites of transcriptional control. The performance of our program was evaluated by comparing the original results of a time course experiment with the findings of our application., Conclusion: DISCLOSE assists researchers in the prokaryotic research community in systematically evaluating results of the application of a range of clustering algorithms to transcriptome data. Different performance measures allow to quickly and comprehensively determine the best suited clustering approach for a given dataset.

A general algorithm for computing Euclidean skeletons of 2D and 3D data sets in linear time is presented. These skeletons are defined in terms of a new concept, called the integer medial axis (IMA) transform. We prove a number of fundamental properties of the IMA skeleton, and compare these with properties of the CMD (centers of maximal disks) skeleton. Several pruning methods for IMA skeletons are introduced (constant, linear and square-root pruning) and their properties studied. The algorithm for computing the IMA skeleton is based upon the feature transform, using a modification of a linear-time algorithm for Euclidean distance transforms. The skeletonization algorithm has a time complexity which is linear in the number of input points, and can be easily parallelized. We present experimental results for several data sets, looking at skeleton quality, memory usage and computation time, both for 2D images and 3D volumes.

Background: Despite a plethora of functional genomic efforts, the function of many genes in sequenced genomes remains unknown. The increasing amount of microarray data for many species allows employing the guilt-by-association principle to predict function on a large scale: genes exhibiting similar expression patterns are more likely to participate in shared biological processes., Results: We developed Prosecutor, an application that enables researchers to rapidly infer gene function based on available gene expression data and functional annotations. Our parameter-free functional prediction method uses a sensitive algorithm to achieve a high association rate of linking genes with unknown function to annotated genes. Furthermore, Prosecutor utilizes additional biological information such as genomic context and known regulatory mechanisms that are specific for prokaryotes. We analyzed publicly available transcriptome data sets and used literature sources to validate putative functions suggested by Prosecutor. We supply the complete results of our analysis for 11 prokaryotic organisms on a dedicated website., Conclusion: The Prosecutor software and supplementary datasets available at http://www.prosecutor.nl allow researchers working on any of the analyzed organisms to quickly identify the putative functions of their genes of interest. A de novo analysis allows new organisms to be studied.

A typical data-driven visualization of electroencephalography (EEG) coherence is a graph layout, with vertices representing electrodes and edges representing significant coherences between electrode signals. A drawback of this layout is its visual clutter for multichannel EEG. To reduce clutter, we define a functional unit (FU) as a data-driven region of interest (ROI). An FU is a spatially connected set of electrodes recording pairwise significantly coherent signals, represented in the coherence graph by a spatially connected clique. Earlier we presented two methods to detect FUs: a maximal clique based (MCB) method (time complexity O(3n/3), with n being the number of vertices) and a more efficient watershed based (WB) method (time complexity O (n2 log n)). To reduce the potential over-segmentation of the WB method, we introduce here an improved WB (IWB) method (time complexity O(n2 log n)). The IWB method merges basins representing FUs during the segmentation if they are spatially connected and if their union is a clique. The WB and IWB methods are both up to a factor of 100,000 faster than the MCB method for a typical multichannel setting with 128 EEG channels, thus making interactive visualization of multichannel EEG coherence possible. Results show that considering the MCB method as the gold standard, the difference between IWB and MCB FU maps is smaller than between WB and MCB FU maps. We also introduce two novel group maps for data-driven group analysis as extensions of the IWB method. First, the group mean coherence map preserves dominant features from a collection of individual FU maps. Second, the group FU size map visualizes the average FU size per electrode across a collection of individual FU maps. Finally, we employ an extensive case study to evaluate the IWB FU map and the two new group maps for data-driven group analysis. Results, in accordance with the conventional findings, indicate differences in EEG coherence between younger and older adults. However, they also suggest that an initial selection of hypothesis-driven ROIs could be extended with additional data-driven ROIs.

Electroencephalography (EEG) coherence provides a quantitative measure of functional brain connectivity which is calculated between pairs of signals as a function of frequency. Without hypotheses, traditional coherence analysis would be cumbersome for high-density EEG which employs a large number of electrodes. One problem is to find the most relevant regions and coherences between those regions in individuals and groups. Therefore, we previously developed a data-driven approach for individual as well as group analyses of high-density EEG coherence. Its data-driven regions of interest (ROIs) are referred to as functional units (FUs) and are defined as spatially connected sets of electrodes that record pairwise significantly coherent signals. Here, we apply our data-driven approach to a case study of mental fatigue. We show that our approach overcomes the severe limitations of conventional hypothesis-driven methods which depend on previous investigations and leads to a selection of coherences of interest taking full advantage of the recordings under investigation. The presented visualization of (group) FU maps provides a very economical data summary of extensive experimental results, which otherwise would be very difficult and time-consuming to assess. Our approach leads to an FU selection which may serve as a basis for subsequent conventional quantitative analysis; thus it complements rather than replaces the hypothesis-driven approach.

Background: We present a simple, data-driven method to extract haemodynamic response functions (HRF) from functional magnetic resonance imaging (fMRI) time series, based on the Fourier-wavelet regularised deconvolution (ForWaRD) technique. HRF data are required for many fMRI applications, such as defining region-specific HRFs, effciently representing a general HRF, or comparing subject-specific HRFs., Results: ForWaRD is applied to fMRI time signals, after removing low-frequency trends by a wavelet-based method, and the output of ForWaRD is a time series of volumes, containing the HRF in each voxel. Compared to more complex methods, this extraction algorithm requires few assumptions (separability of signal and noise in the frequency and wavelet domains and the general linear model) and it is fast (HRF extraction from a single fMRI data set takes about the same time as spatial resampling). The extraction method is tested on simulated event-related activation signals, contaminated with noise from a time series of real MRI images. An application for HRF data is demonstrated in a simple event-related experiment: data are extracted from a region with significant effects of interest in a first time series. A continuous-time HRF is obtained by fitting a nonlinear function to the discrete HRF coeffcients, and is then used to analyse a later time series., Conclusion: With the parameters used in this paper, the extraction method presented here is very robust to changes in signal properties. Comparison of analyses with fitted HRFs and with a canonical HRF shows that a subject-specific, regional HRF significantly improves detection power. Sensitivity and specificity increase not only in the region from which the HRFs are extracted, but also in other regions of interest.

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.

We propose a novel, geometrically adaptive method for surface reconstruction from noisy and sparse point clouds, without orientation information. The method employs a fast convection algorithm to attract the evolving surface towards the data points. The force field in which the surface is convected is based on generalized Coulomb potentials evaluated on an adaptive grid (i.e., an octree) using a fast, hierarchical algorithm. Formulating reconstruction as a convection problem in a velocity field generated by Coulomb potentials offers a number of advantages. Unlike methods which compute the distance from the data set to the implicit surface, which are sensitive to noise due to the very reliance on the distance transform, our method is highly resilient to shot noise since global, generalized Coulomb potentials can be used to disregard the presence of outliers due to noise. Coulomb potentials represent long-range interactions that consider all data points at once, and thus they convey global information which is crucial in the fitting process. Both the spatial and temporal complexities of our spatially-adaptive method are proportional to the size of the reconstructed object, which makes our method compare favorably with respect to previous approaches in terms of speed and flexibility. Experiments with sparse as well as noisy data sets show that the method is capable of delivering crisp and detailed yet smooth surfaces.

Perception of peripherally viewed shapes is impaired when surrounded by similar shapes. This phenomenon is commonly referred to as "crowding". Although studied extensively for perception of characters (mainly letters) and, to a lesser extent, for orientation, little is known about whether and how crowding affects perception of other features. Nevertheless, current crowding models suggest that the effect should be rather general and thus not restricted to letters and orientation. Here, we report on a series of experiments investigating crowding in the following elementary feature dimensions: size, hue, and saturation. Crowding effects in these dimensions were benchmarked against those in the orientation domain. Our primary finding is that all features studied show clear signs of crowding. First, identification thresholds increase with decreasing mask spacing. Second, for all tested features, critical spacing appears to be roughly half the viewing eccentricity and independent of stimulus size, a property previously proposed as the hallmark of crowding. Interestingly, although critical spacings are highly comparable, crowding magnitude differs across features: Size crowding is almost as strong as orientation crowding, whereas the effect is much weaker for saturation and hue. We suggest that future theories and models of crowding should be able to accommodate these differences in crowding effects.

Unlabelled: FIVA (Function Information Viewer and Analyzer) aids researchers in the prokaryotic community to quickly identify relevant biological processes following transcriptome analysis. Our software assists in functional profiling of large sets of genes and generates a comprehensive overview of affected biological processes., Availability: http://bioinformatics.biol.rug.nl/standalone/fiva/

In this paper, we describe a multiscale and multishape morphological method for pattern-based analysis and classification of gray-scale images using connected operators. Compared with existing methods, which use structuring elements, our method has three advantages. First, in our method, the time needed for computing pattern spectra does not depend on the number of scales or shapes used, i.e., the computation time is independent of the dimensions of the pattern spectrum. Second, size and strict shape attributes can be computed, which we use for the construction of joint 2D shape-size pattern spectra. Third, our method is significantly less sensitive to noise and is rotation-invariant. Although rotation invariance can also be approximated by methods using structuring elements at different angles, this tends to be computationally intensive. The classification performance of these methods is discussed using four image sets: Brodatz, COIL-20, COIL-100, and diatoms. The new method obtains better or equal classification performance to the best competitor with a 5 to 9-fold speed gain.

The field of visualization assists data interpretation in many areas, but does not manage all types of data equally well. This holds, in particular, for time-varying multichannel EEG data. No existing method can successfully visualize simultaneous information from all channels in use at all time steps. To address this problem, a new visualization method is presented based on the parallel coordinate method and making use of a tiled organization. This tiled organization employs a two-dimensional row-column representation, rather than a one-dimensional arrangement in columns as used for classical parallel coordinates. The usefulness of the new method, referred to as tiled parallel coordinates (TPC), is demonstrated by a particular type of EEG data. It can be applied to an arbitrary number of time steps, handling the maximum number of channels currently in use. An extensive user evaluation shows that, for a typical EEG assessment task, data evaluation by the TPC method is faster than by an existing clinical EEG visualization method, without loss of information. The generality of the TPC method makes it widely applicable to other time-varying multivariate data types.

Among the various research areas that comprise bioinformatics, systems biology is gaining increasing attention. An important goal of systems biology is the unraveling of dynamic interactions between components of living cells (e. g., proteins, genes). These interactions exist among others on genomic, transcriptomic, proteomic and metabolomic levels. The levels themselves are heavily interconnected, resulting in complex networks of different interacting biological entities. Currently, various bioinformatics tools exist which are able to perform a particular analysis on a particular type of network. Unfortunately, each tool has its own disadvantages hampering it to be used consistently for different types of networks or analytical methods. This paper describes the conceptual development of an open source extensible software framework that supports visualization and exploration of highly complex genomic networks, like metabolic or gene regulatory networks. The focus is on the conceptual foundations, starting from requirements, a description of the state of the art of network visualization systems, and an analysis of their shortcomings. We describe the implementation of some initial modules of the framework and apply them to a biological test case in bacterial regulation, which shows the relevance and feasibility of the proposed approach.

While searching for objects, we combine information from multiple visual modalities. Classical theories of visual search assume that features are processed independently prior to an integration stage. Based on this, one would predict that features that are equally discriminable in single feature search should remain so in conjunction search. We test this hypothesis by examining whether search accuracy in feature search predicts accuracy in conjunction search. Subjects searched for objects combining color and orientation or size; eye movements were recorded. Prior to the main experiment, we matched feature discriminability, making sure that in feature search, 70% of saccades were likely to go to the correct target stimulus. In contrast to this symmetric single feature discrimination performance, the conjunction search task showed an asymmetry in feature discrimination performance: In conjunction search, a similar percentage of saccades went to the correct color as in feature search but much less often to correct orientation or size. Therefore, accuracy in feature search is a good predictor of accuracy in conjunction search for color but not for size and orientation. We propose two explanations for the presence of such asymmetries in conjunction search: the use of conjunctively tuned channels and differential crowding effects for different features.

A multiscale, morphological method for the purpose of shape-based object recognition is presented. A connected operator similar to the morphological hat-transform is defined, and two scale-space representations are built, using the curvature function as the underlying one-dimensional signal. Each peak and valley of the curvature is extracted and described by its maximum and average heights and by its extent and represents an entry in the top or bottom hat-transform scale spaces. We demonstrate object recognition based on hat-transform scale spaces for three large data sets, a set of diatom contours, the set of silhouettes from the MPEG-7 database and the set of two-dimensional views of three-dimensional objects from the COIL-20 database. Our approach outperforms other methods for which comparative results exist.

This paper discusses the assumption of Gaussian noise in the blood-oxygenation-dependent (BOLD) contrast for functional MRI (fMRI). In principle, magnitudes in MRI images follow a Rice distribution. We start by reviewing differences between Rician and Gaussian noise. An analytic expression is derived for the null (resting-state) distribution of the difference between two Rician distributed images. This distribution is shown to be symmetric, and an exact expression for its standard deviation is derived. This distribution can be well approximated by a Gaussian, with very high precision for high SNR, and high precision for lower SNR. Tests on simulated and real MR images show that subtracting the time-series mean in fMRI yields asymmetrically distributed temporal noise. Subtracting a resting-state time series from the first results in symmetric and nearly Gaussian noise. This has important consequences for fMRI analyses using standard statistical tests.

This paper concerns the problem of correcting spin-history artefacts in fMRI data. We focus on the influence of through-plane motion on the history of magnetization. A change in object position will disrupt the tissue's steady-state magnetization. The disruption will propagate to the next few acquired volumes until a new steady state is reached. In this paper we present a simulation of spin-history effects, experimental data, and an automatic two-step algorithm for detecting and correcting spin-history artefacts. The algorithm determines the steady-state distribution of all voxels in a given slice and indicates which voxels need a spin-history correction. The spin-history correction is meant to be applied before standard realignment procedures. To obtain experimental data a special phantom and an MRI compatible motion system were designed. The effect of motion on spin-history is presented for data obtained using this phantom inside a 1.5-T MRI scanner. We show that the presented algorithm is capable of detecting the occurrence of a displacement, and it determines which voxels need a spin-history correction. The results of the phantom study show good agreement with the simulations.

A novel, physically motivated deformable model for shape recovery and segmentation is presented. The model, referred to as the charged-particle model (CPM), is inspired by classical electrodynamics and is based on a simulation of charged particles moving in an electrostatic field. The charges are attracted towards the contours of the objects of interest by an electrostatic field, whose sources are computed based on the gradient-magnitude image. The electric field plays the same role as the potential forces in the snake model, while internal interactions are modeled by repulsive Coulomb forces. We demonstrate the flexibility and potential of the model in a wide variety of settings: shape recovery using manual initialization, automatic segmentation, and skeleton computation. We perform a comparative analysis of the proposed model with the active contour model and show that specific problems of the latter are surmounted by our model. The model is easily extendable to 3D and copes well with noisy images.

A general framework for automatic segmentation of diatom images is presented. This segmentation is a critical first step in contour-based methods for automatic identification of diatoms by computerized image analysis. We review existing results, adapt popular segmentation methods to this difficult problem, and finally develop a method that substantially improves existing results. This method is based on the watershed segmentation from mathematical morphology, and belongs to the class of hybrid segmentation techniques. The novelty of the method is the use of connected operators for the computation and selection of markers, a critical ingredient in the watershed method to avoid over-segmentation. All methods considered were used to extract binary contours from a large database of diatom images, and the quality of the contours was evaluated both visually and based on identification performance., (Copyright 2004 Wiley-Liss, Inc.)

We present a general wavelet-based denoising scheme for functional magnetic resonance imaging (fMRI) data and compare it to Gaussian smoothing, the traditional denoising method used in fMRI analysis. One-dimensional WaveLab thresholding routines were adapted to two-dimensional (2-D) images, and applied to 2-D wavelet coefficients. To test the effect of these methods on the signal-to-noise ratio (SNR), we compared the SNR of 2-D fMRI images before and after denoising, using both Gaussian smoothing and wavelet-based methods. We simulated a fMRI series with a time signal in an active spot, and tested the methods on noisy copies of it. The denoising methods were evaluated in two ways: by the average temporal SNR inside the original activated spot, and by the shape of the spot detected by thresholding the temporal SNR maps. Denoising methods that introduce much smoothness are better suited for low SNRs, but for images of reasonable quality they are not preferable, because they introduce heavy deformations. Wavelet-based denoising methods that introduce less smoothing preserve the sharpness of the images and retain the original shapes of active regions. We also performed statistical parametric mapping on the denoised simulated time series, as well as on a real fMRI data set. False discovery rate control was used to correct for multiple comparisons. The results show that the methods that produce smooth images introduce more false positives. The less smoothing wavelet-based methods, although generating more false negatives, produce a smaller total number of errors than Gaussian smoothing or wavelet-based methods with a large smoothing effect.

We describe a multiresolution extension to maximum intensity projection (MIP) volume rendering, allowing progressive refinement and perfect reconstruction. The method makes use of morphological adjunction pyramids. The pyramidal analysis and synthesis operators are composed of morphological 3-D erosion and dilation, combined with dyadic downsampling for analysis and dyadic upsampling for synthesis. In this case the MIP operator can be interchanged with the synthesis operator. This fact is the key to an efficient multiresolution MIP algorithm, because it allows the computation of the maxima along the line of sight on a coarse level, before applying a two-dimensional synthesis operator to perform reconstruction of the projection image to a finer level. For interpolation and resampling of volume data, which is required to deal with arbitrary view directions, morphological sampling is used, an interpolation method well adapted to the nonlinear character of MIP. The structure of the resulting multiresolution rendering algorithm is very similar to wavelet splatting, the main differences being that (i) linear summation of voxel values is replaced by maximum computation, and (ii) linear wavelet filters are replaced by nonlinear morphological filters.