Visualization is a critical component of neuroimaging, and how to best view data that is naturally three dimensional is a long standing question in neuroscience. Many approaches, programs, and techniques have been developed specifically for neuroimaging. However, exploration of 3D information through a 2D screen is inherently limited. Many neuroscientific researchers hope that with the recent commercialization and popularization of VR, it can offer the next-step in data visualization and exploration. Neuro Imaging in Virtual Reality (NIVR), is a visualization suite that employs various immersive visualizations to represent neuroimaging information in VR. Some established techniques, such as raymarching volume visualization, are paired with newer techniques, such as near-field rendering, to provide a broad basis of how we can leverage VR to improve visualization and navigation of neuroimaging data. Several of the neuroscientific visualization approaches presented are, to our knowledge, the first of their kind. NIVR offers not only an exploration of neuroscientific data visualization, but also a tool to expose and educate the public regarding recent advancements in the field of neuroimaging. By providing an engaging experience to explore new techniques and discoveries in neuroimaging, we hope to spark scientific interest through a broad audience. Furthermore, neuroimaging offers deep and expansive datasets; a single scan can involve several gigabytes of information. Visualization and exploration of this type of information can be challenging, and real-time exploration of this information in VR even more so. NIVR explores pathways which make this possible, and offers preliminary stereo visualizations of these types of massive data.

The USC Stevens Neuroimaging and Informatics Institute in the Laboratory of Neuro Imaging (http://loni.usc.edu) has the largest collection/repository of neuroanatomical MRI scans in the world and is at the forefront of both brain imaging and data storage/processing technology. One of our workflow processes involves algorithmic segmentation of MRI scans into labeled anatomical regions (using FreeSurfer, currently the best software for this purpose). This algorithm is imprecise, and users must tediously correct errors manually by using a mouse and keyboard to edit individual MRI slices at a time. We demonstrate preliminary work to improve efficiency of this task by translating it into 3 dimensions and utilizing virtual reality user interfaces to edit multiple slices of data simultaneously.

Big data workflows often require the assembly and exchange of complex, multi-element datasets. For example, in biomedical applications, the input to an analytic pipeline can be a dataset consisting thousands of images and genome sequences assembled from diverse repositories, requiring a description of the contents of the dataset in a concise and unambiguous form. Typical approaches to creating datasets for big data workflows assume that all data reside in a single location, requiring costly data marshaling and permitting errors of omission and commission because dataset members are not explicitly specified. We address these issues by proposing simple methods and tools for assembling, sharing, and analyzing large and complex datasets that scientists can easily integrate into their daily workflows. These tools combine a simple and robust method for describing data collections (BDBags), data descriptions (Research Objects), and simple persistent identifiers (Minids) to create a powerful ecosystem of tools and services for big data analysis and sharing. We present these tools and use biomedical case studies to illustrate their use for the rapid assembly, sharing, and analysis of large datasets.

Multiple testing for statistical maps remains a critical and challenging problem in brain mapping. Since the false discovery rate (FDR) criterion was introduced to the neuroimaging community a decade ago, many variations have been proposed, mainly to enhance detection power. However, a fundamental geometrical property known as transformation invariance has not been adequately addressed, especially for the voxel-wise FDR. Correction of multiple testing applied after spatial transformation is not necessarily equivalent to transformation applied after correction in the original space. Without the invariance property, assigning different testing spaces will yield different results. We find that normalized residuals of linear models with Gaussian noises are uniformly distributed on a unit high-dimensional sphere, independent of t-statistics and F-statistics. By defining volumetric measure in the hyper-spherical space mapped by normalized residuals, instead of the image's Euclidean space, we can achieve invariant control of the FDR under diffeomorphic transformation. This hyper-spherical measure also reflects intrinsic "volume of randomness" in signals. Experiments with synthetic, semi-synthetic and real images demonstrate that our method significantly reduces FDR inconsistency introduced by the choice of testing spaces.

Modern biomedical data collection is generating exponentially more data in a multitude of formats. This flood of complex data poses significant opportunities to discover and understand the critical interplay among such diverse domains as genomics, proteomics, metabolomics, and phenomics, including imaging, biometrics, and clinical data. The Big Data for Discovery Science Center is taking an "-ome to home" approach to discover linkages between these disparate data sources by mining existing databases of proteomic and genomic data, brain images, and clinical assessments. In support of this work, the authors developed new technological capabilities that make it easy for researchers to manage, aggregate, manipulate, integrate, and model large amounts of distributed data. Guided by biological domain expertise, the Center's computational resources and software will reveal relationships and patterns, aiding researchers in identifying biomarkers for the most confounding conditions and diseases, such as Parkinson's and Alzheimer's.

Workflow reuse is a major benefit of workflow systems and shared workflow repositories, but there are barely any studies that quantify the degree of reuse of workflows or the practical barriers that may stand in the way of successful reuse. In our own work, we hypothesize that defining workflow fragments improves reuse, since end-to-end workflows may be very specific and only partially reusable by others. This paper reports on a study of the current use of workflows and workflow fragments in labs that use the LONI Pipeline, a popular workflow system used mainly for neuroimaging research that enables users to define and reuse workflow fragments. We present an overview of the benefits of workflows and workflow fragments reported by users in informal discussions. We also report on a survey of researchers in a lab that has the LONI Pipeline installed, asking them about their experiences with reuse of workflow fragments and the actual benefits they perceive. This leads to quantifiable indicators of the reuse of workflows and workflow fragments in practice. Finally, we discuss barriers to further adoption of workflow fragments and workflow reuse that motivate further work.

Scientific workflows provide the means to define, execute and reproduce computational experiments. However, reusing existing workflows still poses challenges for workflow designers. Workflows are often too large and too specific to reuse in their entirety, so reuse is more likely to happen for fragments of workflows. These fragments may be identified manually by users as sub-workflows, or detected automatically. In this paper we present the FragFlow approach, which detects workflow fragments automatically by analyzing existing workflow corpora with graph mining algorithms. FragFlow detects the most common workflow fragments, links them to the original workflows and visualizes them. We evaluate our approach by comparing FragFlow results against user-defined sub-workflows from three different corpora of the LONI Pipeline system. Based on this evaluation, we discuss how automated workflow fragment detection could facilitate workflow reuse.

Diffusion tensor imaging is widely used in brain connectivity research. As more and more studies recruit large numbers of subjects, it is important to design registration methods which are not only theoretically rigorous, but also computationally efficient. However, the requirement of reorienting diffusion tensors complicates and considerably slows down registration procedures, due to the correlated impacts of registration forces at adjacent voxel locations. Based on the diffeomorphic Demons algorithm (Vercauteren , 2009), we propose a fast local trust region algorithm for handling inseparable registration forces for quadratic energy functions. The method guarantees that, at any time and at any voxel location, the velocity is always within its local trust region. This local regularization allows efficient calculation of the transformation update with numeric integration instead of completely solving a large linear system at every iteration. It is able to incorporate exact reorientation and regularization into the velocity optimization, and preserve the linear complexity of the diffeomorphic Demons algorithm. In an experiment with 84 diffusion tensor images involving both pair-wise and group-wise registrations, the proposed algorithm achieves better registration in comparison with other methods solving large linear systems (Yeo , 2009). At the same time, this algorithm reduces the computation time and memory demand tenfold.

In this paper, we present a novel approach for the intrinsic mapping of anatomical surfaces and its application in brain mapping research. Using the Laplace-Beltrami eigen-system, we represent each surface with an isometry invariant embedding in a high dimensional space. The key idea in our system is that we realize surface deformation in the embedding space via the iterative optimization of a conformal metric without explicitly perturbing the surface or its embedding. By minimizing a distance measure in the embedding space with metric optimization, our method generates a conformal map directly between surfaces with highly uniform metric distortion and the ability of aligning salient geometric features. Besides pairwise surface maps, we also extend the metric optimization approach for group-wise atlas construction and multi-atlas cortical label fusion. In experimental results, we demonstrate the robustness and generality of our method by applying it to map both cortical and hippocampal surfaces in population studies. For cortical labeling, our method achieves excellent performance in a cross-validation experiment with 40 manually labeled surfaces, and successfully models localized brain development in a pediatric study of 80 subjects. For hippocampal mapping, our method produces much more significant results than two popular tools on a multiple sclerosis study of 109 subjects.

In this paper we present a novel system for the automated reconstruction of cortical surfaces from T1-weighted magnetic resonance images. At the core of our system is a unified Reeb analysis framework for the detection and removal of geometric and topological outliers on tissue boundaries. Using intrinsic Reeb analysis, our system can pinpoint the location of spurious branches and topological outliers, and correct them with localized filtering using information from both image intensity distributions and geometric regularity. In this system, we have also developed enhanced tissue classification with Hessian features for improved robustness to image inhomogeneity, and adaptive interpolation to achieve sub-voxel accuracy in reconstructed surfaces. By integrating these novel developments, we have a system that can automatically reconstruct cortical surfaces with improved quality and dramatically reduced computational cost as compared with the popular FreeSurfer software. In our experiments, we demonstrate on 40 simulated MR images and the MR images of 200 subjects from two databases: the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and International Consortium of Brain Mapping (ICBM), the robustness of our method in large scale studies. In comparisons with FreeSurfer, we show that our system is able to generate surfaces that better represent cortical anatomy and produce thickness features with higher statistical power in population studies.

The Center for Computational Biology (CCB) is a multidisciplinary program where biomedical scientists, engineers, and clinicians work jointly to combine modern mathematical and computational techniques, to perform phenotypic and genotypic studies of biological structure, function, and physiology in health and disease. CCB has developed a computational framework built around the Manifold Atlas, an integrated biomedical computing environment that enables statistical inference on biological manifolds. These manifolds model biological structures, features, shapes, and flows, and support sophisticated morphometric and statistical analyses. The Manifold Atlas includes tools, workflows, and services for multimodal population-based modeling and analysis of biological manifolds. The broad spectrum of biomedical topics explored by CCB investigators include the study of normal and pathological brain development, maturation and aging, discovery of associations between neuroimaging and genetic biomarkers, and the modeling, analysis, and visualization of biological shape, form, and size. CCB supports a wide range of short-term and long-term collaborations with outside investigators, which drive the center's computational developments and focus the validation and dissemination of CCB resources to new areas and scientific domains.

We present a diffeomorphic approach for constructing intrinsic shape atlases of sulci on the human cortex. Sulci are represented as square-root velocity functions of continuous open curves in R³, and their shapes are studied as functional representations of an infinite-dimensional sphere. This spherical manifold has some advantageous properties--it is equipped with a Riemannian L² metric on the tangent space and facilitates computational analyses and correspondences between sulcal shapes. Sulcal shape mapping is achieved by computing geodesics in the quotient space of shapes modulo scales, translations, rigid rotations, and reparameterizations. The resulting sulcal shape atlas preserves important local geometry inherently present in the sample population. The sulcal shape atlas is integrated in a cortical registration framework and exhibits better geometric matching compared to the conventional euclidean method. We demonstrate experimental results for sulcal shape mapping, cortical surface registration, and sulcal classification for two different surface extraction protocols for separate subject populations.

In brain mapping research, parameterized 3-D surface models are of great interest for statistical comparisons of anatomy, surface-based registration, and signal processing. Here, we introduce the theories of continuous and discrete surface Ricci flow, which can create Riemannian metrics on surfaces with arbitrary topologies with user-defined Gaussian curvatures. The resulting conformal parameterizations have no singularities and they are intrinsic and stable. First, we convert a cortical surface model into a multiple boundary surface by cutting along selected anatomical landmark curves. Secondly, we conformally parameterize each cortical surface to a parameter domain with a user-designed Gaussian curvature arrangement. In the parameter domain, a shape index based on conformal invariants is computed, and inter-subject cortical surface matching is performed by solving a constrained harmonic map. We illustrate various target curvature arrangements and demonstrate the stability of the method using longitudinal data. To map statistical differences in cortical morphometry, we studied brain asymmetry in 14 healthy control subjects. We used a manifold version of Hotelling's T(2) test, applied to the Jacobian matrices of the surface parameterizations. A permutation test, along with the cumulative distribution of p-values, were used to estimate the overall statistical significance of differences. The results show our algorithm's power to detect subtle group differences in cortical surfaces.

Corpus callosum (CC) is an important structure in human brain anatomy. In this work, we propose a fully automated and robust approach to extract corpus callosum from T1-weighted structural MR images. The novelty of our method is composed of two key steps. In the first step, we find an initial guess for the curve representation of CC by using the zero level set of the first nontrivial Laplace-Beltrami (LB) eigenfunction on the white matter surface. In the second step, the initial curve is deformed toward the final solution with a geodesic curvature flow on the white matter surface. For numerical solution of the geodesic curvature flow on surfaces, we represent the contour implicitly on a triangular mesh and develop efficient numerical schemes based on finite element method. Because our method depends only on the intrinsic geometry of the white matter surface, it is robust to orientation differences of the brain across population. In our experiments, we validate the proposed algorithm on 32 brains from a clinical study of multiple sclerosis disease and demonstrate that the accuracy of our results.

We present a novel edge preserved interpolation scheme for fast upsampling of natural images. The proposed piecewise hyperbolic operator uses a slope-limiter function that conveniently lends itself to higher-order approximations and is responsible for restricting spatial oscillations arising due to the edges and sharp details in the image. As a consequence the upsampled image not only exhibits enhanced edges, and discontinuities across boundaries, but also preserves smoothly varying features in images. Experimental results show an improvement in the PSNR compared to typical cubic, and spline-based interpolation approaches.

BACKGROUND: Contemporary informatics and genomics research require efficient, flexible and robust management of large heterogeneous data, advanced computational tools, powerful visualization, reliable hardware infrastructure, interoperability of computational resources, and detailed data and analysis-protocol provenance. The Pipeline is a client-server distributed computational environment that facilitates the visual graphical construction, execution, monitoring, validation and dissemination of advanced data analysis protocols. RESULTS: This paper reports on the applications of the LONI Pipeline environment to address two informatics challenges - graphical management of diverse genomics tools, and the interoperability of informatics software. Specifically, this manuscript presents the concrete details of deploying general informatics suites and individual software tools to new hardware infrastructures, the design, validation and execution of new visual analysis protocols via the Pipeline graphical interface, and integration of diverse informatics tools via the Pipeline eXtensible Markup Language syntax. We demonstrate each of these processes using several established informatics packages (e.g., miBLAST, EMBOSS, mrFAST, GWASS, MAQ, SAMtools, Bowtie) for basic local sequence alignment and search, molecular biology data analysis, and genome-wide association studies. These examples demonstrate the power of the Pipeline graphical workflow environment to enable integration of bioinformatics resources which provide a well-defined syntax for dynamic specification of the input/output parameters and the run-time execution controls. CONCLUSIONS: The LONI Pipeline environment http://pipeline.loni.ucla.edu provides a flexible graphical infrastructure for efficient biomedical computing and distributed informatics research. The interactive Pipeline resource manager enables the utilization and interoperability of diverse types of informatics resources. The Pipeline client-server model provides computational power to a broad spectrum of informatics investigators--experienced developers and novice users, user with or without access to advanced computational-resources (e.g., Grid, data), as well as basic and translational scientists. The open development, validation and dissemination of computational networks (pipeline workflows) facilitates the sharing of knowledge, tools, protocols and best practices, and enables the unbiased validation and replication of scientific findings by the entire community.

OBJECTIVE: As biomedical technology becomes increasingly sophisticated, researchers can probe ever more subtle effects with the added requirement that the investigation of small effects often requires the acquisition of large amounts of data. In biomedicine, these data are often acquired at, and later shared between, multiple sites. There are both technological and sociological hurdles to be overcome for data to be passed between researchers and later made accessible to the larger scientific community. The goal of the Biomedical Informatics Research Network (BIRN) is to address the challenges inherent in biomedical data sharing. MATERIALS AND METHODS: BIRN tools are grouped into 'capabilities' and are available in the areas of data management, data security, information integration, and knowledge engineering. BIRN has a user-driven focus and employs a layered architectural approach that promotes reuse of infrastructure. BIRN tools are designed to be modular and therefore can work with pre-existing tools. BIRN users can choose the capabilities most useful for their application, while not having to ensure that their project conforms to a monolithic architecture. RESULTS: BIRN has implemented a new software-based data-sharing infrastructure that has been put to use in many different domains within biomedicine. BIRN is actively involved in outreach to the broader biomedical community to form working partnerships. CONCLUSION: BIRN's mission is to provide capabilities and services related to data sharing to the biomedical research community. It does this by forming partnerships and solving specific, user-driven problems whose solutions are then available for use by other groups.

We present an intrinsic framework for constructing sulcal shape atlases on the human cortex. We propose the analysis of sulcal and gyral patterns by representing them by continuous open curves in ℝ(3). The space of such curves, also termed as the shape manifold is equipped with a Riemannian L(2) metric on the tangent space, and shows desirable properties while matching shapes of sulci. On account of the spherical nature of the shape space, geodesics between shapes can be computed analytically. Additionally, we also present an optimization approach that computes geodesics in the quotient space of shapes modulo rigid rotations and reparameterizations. We also integrate the elastic shape model into a surface registration framework for a population of 176 subjects, and show a considerable improvement in the constructed surface atlases.

For various 3D shape analysis tasks, the Laplace-Beltrami(LB) embedding has become increasingly popular as it enables the efficient comparison of shapes based on intrinsic geometry. One fundamental difficulty in using the LB embedding, however, is the ambiguity in the eigen-system, and it is conventionally only handled in a heuristic way. In this work, we propose a novel and intrinsic metric, the spectral l2-distance, to overcome this difficulty. We prove mathematically that this new distance satisfies the conditions of a rigorous metric. Using the resulting optimal embedding determined by the spectral l2-distance, we can perform both local and global shape analysis intrinsically in the embedding space. We demonstrate this by developing a template matching approach in the optimal embedding space to solve the challenging problem of identifying major sulci on vervet cortical surfaces. In our experiments, we validate the robustness of our method by the successful identification of major sulcal lines on a large data set of 698 cortical surfaces and illustrate its potential in brain mapping studies.

BACKGROUND: Digital atlases provide a common semantic and spatial coordinate system that can be leveraged to compare, contrast, and correlate data from disparate sources. As the quality and amount of biological data continues to advance and grow, searching, referencing, and comparing this data with a researcher's own data is essential. However, the integration process is cumbersome and time-consuming due to misaligned data, implicitly defined associations, and incompatible data sources. This work addressing these challenges by providing a unified and adaptable environment to accelerate the workflow to gather, align, and analyze the data. RESULTS: The MouseBIRN Atlasing Toolkit (MBAT) project was developed as a cross-platform, free open-source application that unifies and accelerates the digital atlas workflow. A tiered, plug-in architecture was designed for the neuroinformatics and genomics goals of the project to provide a modular and extensible design. MBAT provides the ability to use a single query to search and retrieve data from multiple data sources, align image data using the user's preferred registration method, composite data from multiple sources in a common space, and link relevant informatics information to the current view of the data or atlas. The workspaces leverage tool plug-ins to extend and allow future extensions of the basic workspace functionality. A wide variety of tool plug-ins were developed that integrate pre-existing as well as newly created technology into each workspace. Novel atlasing features were also developed, such as supporting multiple label sets, dynamic selection and grouping of labels, and synchronized, context-driven display of ontological data. CONCLUSIONS: MBAT empowers researchers to discover correlations among disparate data by providing a unified environment for bringing together distributed reference resources, a user's image data, and biological atlases into the same spatial or semantic context. Through its extensible tiered plug-in architecture, MBAT allows researchers to customize all platform components to quickly achieve personalized workflows.

We compared four automated methods for hippocampal segmentation using different machine learning algorithms: 1) hierarchical AdaBoost, 2) support vector machines (SVM) with manual feature selection, 3) hierarchical SVM with automated feature selection (Ada-SVM), and 4) a publicly available brain segmentation package (FreeSurfer). We trained our approaches using T1-weighted brain MRIs from 30 subjects [10 normal elderly, 10 mild cognitive impairment (MCI), and 10 Alzheimer's disease (AD)], and tested on an independent set of 40 subjects (20 normal, 20 AD). Manually segmented gold standard hippocampal tracings were available for all subjects (training and testing). We assessed each approach's accuracy relative to manual segmentations, and its power to map AD effects. We then converted the segmentations into parametric surfaces to map disease effects on anatomy. After surface reconstruction, we computed significance maps, and overall corrected p-values, for the 3-D profile of shape differences between AD and normal subjects. Our AdaBoost and Ada-SVM segmentations compared favorably with the manual segmentations and detected disease effects as well as FreeSurfer on the data tested. Cumulative p-value plots, in conjunction with the false discovery rate method, were used to examine the power of each method to detect correlations with diagnosis and cognitive scores. We also evaluated how segmentation accuracy depended on the size of the training set, providing practical information for future users of this technique.

In medical shape analysis, a critical problem is reconstructing a smooth surface of correct topology from a binary mask that typically has spurious features due to segmentation artifacts. The challenge is the robust removal of these outliers without affecting the accuracy of other parts of the boundary. In this paper, we propose a novel approach for this problem based on the Laplace-Beltrami (LB) eigen-projection and properly designed boundary deformations. Using the metric distortion during the LB eigen-projection, our method automatically detects the location of outliers and feeds this information to a well-composed and topology-preserving deformation. By iterating between these two steps of outlier detection and boundary deformation, we can robustly filter out the outliers without moving the smooth part of the boundary. The final surface is the eigen-projection of the filtered mask boundary that has the correct topology, desired accuracy and smoothness. In our experiments, we illustrate the robustness of our method on different input masks of the same structure, and compare with the popular SPHARM tool and the topology preserving level set method to show that our method can reconstruct accurate surface representations without introducing artificial oscillations. We also successfully validate our method on a large data set of more than 900 hippocampal masks and demonstrate that the reconstructed surfaces retain volume information accurately.

In this paper, we propose multivariate tensor-based surface morphometry, a new method for surface analysis, using holomorphic differentials; we also apply it to study brain anatomy. Differential forms provide a natural way to parameterize 3D surfaces, but the multivariate statistics of the resulting surface metrics have not previously been investigated. We computed new statistics from the Riemannian metric tensors that retain the full information in the deformation tensor fields. We present the canonical holomorphic one-forms with improved numerical accuracy and computational efficiency. We applied this framework to 3D MRI data to analyze hippocampal surface morphometry in Alzheimer's Disease (AD; 12 subjects), lateral ventricular surface morphometry in HIV/AIDS (11 subjects) and biomarkers in lateral ventricles in HIV/AIDS (11 subjects). Experimental results demonstrated that our method powerfully detected brain surface abnormalities. Multivariate statistics on the local tensors outperformed other TBM methods including analysis of the Jacobian determinant, the largest eigenvalue, or the pair of eigenvalues, of the surface Jacobian matrix.

Two surfaces are conformally equivalent if there exists a bijective angle-preserving map between them. The Teichmüller space for surfaces with the same topology is a finite-dimensional manifold, where each point represents a conformal equivalence class, and the conformal map is homotopic to the identity map. In this paper, we propose a novel method to apply conformal equivalence based shape index to study brain morphometry. The shape index is defined based on Teichmüller space coordinates. It is intrinsic, and invariant under conformal transformations, rigid motions and scaling. It is also simple to compute; no registration of surfaces is needed. Using the Yamabe flow method, we can conformally map a genus-zero open boundary surface to the Poincaré disk. The shape indices that we compute are the lengths of a special set of geodesics under hyperbolic metric. By computing and studying this shape index and its statistical behavior, we can analyze differences in anatomical morphometry due to disease or development. Study on twin lateral ventricular surface data shows it may help detect generic influence on lateral ventricular shapes. In leave-one-out validation tests, we achieved 100% accurate classification (versus only 68% accuracy for volume measures) in distinguishing 11 HIV/AIDS individuals from 8 healthy control subjects, based on Teichmüller coordinates for lateral ventricular surfaces extracted from their 3D MRI scans.Our conformal invariants, the Teichmüller coordinates, successfully classified all lateral ventricular surfaces, showing their promise for analyzing anatomical surface morphometry.

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brainwide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brainwide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open-access data repository; compatibility with existing resources; and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.

We introduce a fluid mechanics based tractography method for estimating the most likely connection paths between points in diffusion tensor imaging (DTI) volumes. We customize the Navier-Stokes equations to include information from the diffusion tensor and simulate an artificial fluid flow through the DTI image volume. We then estimate the most likely connection paths between points in the DTI volume using a metric derived from the fluid velocity vector field. We validate our algorithm using digital DTI phantoms based on a helical shape. Our method segmented the structure of the phantom with less distortion than was produced using implementations of heat-based partial differential equation (PDE) and streamline based methods. In addition, our method was able to successfully segment divergent and crossing fiber geometries, closely following the ideal path through a digital helical phantom in the presence of multiple crossing tracts. To assess the performance of our algorithm on anatomical data, we applied our method to DTI volumes from normal human subjects. Our method produced paths that were consistent with both known anatomy and directionally encoded color images of the DTI dataset.

In this paper, we propose an automated approach for the joint detection of major sulci on cortical surfaces. By representing sulci as nodes in a graphical model, we incorporate Markovian relations between sulci and formulate their detection as a maximum a posteriori (MAP) estimation problem over the joint space of major sulci. To make the inference tractable, a sample space with a finite number of candidate curves is automatically generated at each node based on the Hamilton-Jacobi skeleton of sulcal regions. Using the AdaBoost algorithm, we learn both individual and pairwise shape priors of sulcal curves from training data, which are then used to define potential functions in the graphical model based on the connection between AdaBoost and logistic regression. Finally belief propagation is used to perform the MAP inference and select the joint detection results from the sample spaces of candidate curves. In our experiments, we quantitatively validate our algorithm with manually traced curves and demonstrate the automatically detected curves can capture the main body of sulci very accurately. A comparison with independently detected results is also conducted to illustrate the advantage of the joint detection approach.

This paper describes a coarse-to-fine learning based image registration algorithm which has particular advantages in dealing with multi-modality images. Many existing image registration algorithms [18] use a few designed terms or mutual information to measure the similarity between image pairs. Instead, we push the learning aspect by selecting and fusing a large number of features for measuring the similarity. Moreover, the similarity measure is carried in a coarse-to-fine strategy: global similarity measure is first performed to roughly locate the component, we then learn/compute similarity on the local image patches to capture the fine level information. When estimating the transformation parameters, we also engage a coarse-to-fine strategy. Off-the-shelf interest point detectors such as SIFT [12] have degraded results on medical images. We further push the learning idea to extract the main structures/landmarks. Our algorithm is illustrated on three applications: (1) registration of mouse brain images of different modalities, (2) registering human brain image of MRI T1 and T2 images, (3) faces of different expressions. We show greatly improved results over the existing algorithms based on either mutual information or geometric structures.

Automatically segmenting subcortical structures in brain im ages has the potential to greatly accelerate drug trials and population studies of disease. Here we propose an automatic subcortical segmentation algorithm using the auto context model. Unlike many segmentation algorithms that separately compute a shape prior and an image appearance model, we develop a framework based on machine learning to learn a unified appearance and context model. We trained our algorithm to segment the hippocampus and tested it on 83 brain MRIs (of 35 Alzheimer's disease patients, 22 with mild cognitive impairment, and 26 normal healthy controls). Using standard distance and overlap metrics, the auto context model method significantly outperformed simpler learning-based algorithms (using AdaBoost alone) and the FreeSurfer system. In tests on a public domain dataset designed to validate segmentation [1], our new algorithm also greatly improved upon a recently-proposed hybrid discriminative/generative approach [2], which was among the top three that performed comparably in a recent head-to-head competition.

We apply an information-theoretic cost metric, the symmetrized Kullback-Leibler (sKL) divergence, or J-divergence, to fluid registration of diffusion tensor images. The difference between diffusion tensors is quantified based on the sKL-divergence of their associated probability density functions (PDFs). Three-dimensional DTI data from 34 subjects were fluidly registered to an optimized target image. To allow large image deformations but preserve image topology, we regularized the flow with a large-deformation diffeomorphic mapping based on the kinematics of a Navier-Stokes fluid. A driving force was developed to minimize the J-divergence between the deforming source and target diffusion functions, while reorienting the flowing tensors to preserve fiber topography. In initial experiments, we showed that the sKL-divergence based on full diffusion PDFs is adaptable to higher-order diffusion models, such as high angular resolution diffusion imaging (HARDI). The sKL-divergence was sensitive to subtle differences between two diffusivity profiles, showing promise for nonlinear registration applications and multisubject statistical analysis of HARDI data.

This paper investigates the performance of a new multivariate method for tensor-based morphometry (TBM). Statistics on Riemannian manifolds are developed that exploit the full information in deformation tensor fields. In TBM, multiple brain images are warped to a common neuroanatomical template via 3-D nonlinear registration; the resulting deformation fields are analyzed statistically to identify group differences in anatomy. Rather than study the Jacobian determinant (volume expansion factor) of these deformations, as is common, we retain the full deformation tensors and apply a manifold version of Hotelling's $T(2) test to them, in a Log-Euclidean domain. In 2-D and 3-D magnetic resonance imaging (MRI) data from 26 HIV/AIDS patients and 14 matched healthy subjects, we compared multivariate tensor analysis versus univariate tests of simpler tensor-derived indices: the Jacobian determinant, the trace, geodesic anisotropy, and eigenvalues of the deformation tensor, and the angle of rotation of its eigenvectors. We detected consistent, but more extensive patterns of structural abnormalities, with multivariate tests on the full tensor manifold. Their improved power was established by analyzing cumulative p-value plots using false discovery rate (FDR) methods, appropriately controlling for false positives. This increased detection sensitivity may empower drug trials and large-scale studies of disease that use tensor-based morphometry.

In this paper, we propose a new method to construct graphical representations of cortical folding patterns by computing skeletons on triangulated cortical surfaces. In our approach, a cortical surface is first partitioned into sulcal and gyral regions via the solution of a variational problem using graph cuts, which can guarantee global optimality. After that, we extend the method of Hamilton-Jacobi skeleton [1] to subsets of triangulated surfaces, together with a geometrically intuitive pruning process that can trade off between skeleton complexity and the completeness of representing folding patterns. Compared with previous work that uses skeletons of 3-D volumes to represent sulcal patterns, the skeletons on cortical surfaces can be easily decomposed into branches and provide a simpler way to construct graphical representations of cortical morphometry. In our experiments, we demonstrate our method on two different cortical surface models, its ability of capturing major sulcal patterns and its application to compute skeletons of gyral regions.

In this paper, a hybrid discriminative/generative model for brain anatomical structure segmentation is proposed. The learning aspect of the approach is emphasized. In the discriminative appearance models, various cues such as intensity and curvatures are combined to locally capture the complex appearances of different anatomical structures. A probabilistic boosting tree (PBT) framework is adopted to learn multiclass discriminative models that combine hundreds of features across different scales. On the generative model side, both global and local shape models are used to capture the shape information about each anatomical structure. The parameters to combine the discriminative appearance and generative shape models are also automatically learned. Thus, low-level and high-level information is learned and integrated in a hybrid model. Segmentations are obtained by minimizing an energy function associated with the proposed hybrid model. Finally, a grid-face structure is designed to explicitly represent the 3-D region topology. This representation handles an arbitrary number of regions and facilitates fast surface evolution. Our system was trained and tested on a set of 3-D magnetic resonance imaging (MRI) volumes and the results obtained are encouraging.

Maps of local tissue compression or expansion are often computed by comparing magnetic resonance imaging (MRI) scans using nonlinear image registration. The resulting changes are commonly analyzed using tensor-based morphometry to make inferences about anatomical differences, often based on the Jacobian map, which estimates local tissue gain or loss. Here, we provide rigorous mathematical analyses of the Jacobian maps, and use themto motivate a new numerical method to construct unbiased nonlinear image registration. First, we argue that logarithmic transformation is crucial for analyzing Jacobian values representing morphometric differences. We then examine the statistical distributions of log-Jacobian maps by defining the Kullback-Leibler (KL) distance on material density functions arising in continuum-mechanical models. With this framework, unbiased image registration can be constructed by quantifying the symmetric KL-distance between the identity map and the resulting deformation. Implementation details, addressing the proposed unbiased registration as well as the minimization of symmetric image matching functionals, are then discussed and shown to be applicable to other registration methods, such as inverse consistent registration. In the results section, we test the proposed framework, as well as present an illustrative application mapping detailed 3-D brain changes in sequential magnetic resonance imaging scans of a patient diagnosed with semantic dementia. Using permutation tests, we show that the symmetrization of image registration statistically reduces skewness in the log-Jacobian map.

Finite mixture models (FMMs) are an indispensable tool for unsupervised classification in brain imaging. Fitting an FMM to the data leads to a complex optimization problem. This optimization problem is difficult to solve by standard local optimization methods, such as the expectation-maximization (EM) algorithm, if a principled initialization is not available. In this paper, we propose a new global optimization algorithm for the FMM parameter estimation problem, which is based on real coded genetic algorithms. Our specific contributions are two-fold: 1) we propose to use blended crossover in order to reduce the premature convergence problem to its minimum and 2) we introduce a completely new permutation operator specifically meant for the FMM parameter estimation. In addition to improving the optimization results, the permutation operator allows for imposing biologically meaningful constraints to the FMM parameter values. We also introduce a hybrid of the genetic algorithm and the EM algorithm for efficient solution of multidimensional FMM fitting problems. We compare our algorithm to the self-annealing EM-algorithm and a standard real coded genetic algorithm with the voxel classification tasks within the brain imaging. The algorithms are tested on synthetic data as well as real three-dimensional image data from human magnetic resonance imaging, positron emission tomography, and mouse brain MRI. The tissue classification results by our method are shown to be consistently more reliable and accurate than with the competing parameter estimation methods.

It is important to detect and extract the major cortical sulci from brain images, but manually annotating these sulci is a time-consuming task and requires the labeler to follow complex protocols. This paper proposes a learning-based algorithm for automated extraction of the major cortical sulci from magnetic resonance imaging (MRI) volumes and cortical surfaces. Unlike alternative methods for detecting the major cortical sulci, which use a small number of predefined rules based on properties of the cortical surface such as the mean curvature, our approach learns a discriminative model using the probabilistic boosting tree algorithm (PBT). PBT is a supervised learning approach which selects and combines hundreds of features at different scales, such as curvatures, gradients and shape index. Our method can be applied to either MRI volumes or cortical surfaces. It first outputs a probability map which indicates how likely each voxel lies on a major sulcal curve. Next, it applies dynamic programming to extract the best curve based on the probability map and a shape prior. The algorithm has almost no parameters to tune for extracting different major sulci. It is very fast (it runs in under 1 min per sulcus including the time to compute the discriminative models) due to efficient implementation of the features (e.g., using the integral volume to rapidly compute the responses of 3-D Haar filters). Because the algorithm can be applied to MRI volumes directly, there is no need to perform preprocessing such as tissue segmentation or mapping to a canonical space. The learning aspect of our approach makes the system very flexible and general. For illustration, we use volumes of the right hemisphere with several major cortical sulci manually labeled. The algorithm is tested on two groups of data, including some brains from patients with Williams Syndrome, and the results are very encouraging.

In medical imaging, parameterized 3-D surface models are useful for anatomical modeling and visualization, statistical comparisons of anatomy, and surface-based registration and signal processing. Here we introduce a parameterization method based on Riemann surface structure, which uses a special curvilinear net structure (conformal net) to partition the surface into a set of patches that can each be conformally mapped to a parallelogram. The resulting surface subdivision and the parameterizations of the components are intrinsic and stable (their solutions tend to be smooth functions and the boundary conditions of the Dirichlet problem can be enforced). Conformal parameterization also helps transform partial differential equations (PDEs) that may be defined on 3-D brain surface manifolds to modified PDEs on a two-dimensional parameter domain. Since the Jacobian matrix of a conformal parameterization is diagonal, the modified PDE on the parameter domain is readily solved. To illustrate our techniques, we computed parameterizations for several types of anatomical surfaces in 3-D magnetic resonance imaging scans of the brain, including the cerebral cortex, hippocampi, and lateral ventricles. For surfaces that are topologically homeomorphic to each other and have similar geometrical structures, we show that the parameterization results are consistent and the subdivided surfaces can be matched to each other. Finally, we present an automatic sulcal landmark location algorithm by solving PDEs on cortical surfaces. The landmark detection results are used as constraints for building conformal maps between surfaces that also match explicitly defined landmarks.

We propose a novel adaptive approach based on the Reproducing Kernel Particle Method (RKPM) to extract the cortical surfaces of the brain from three-dimensional (3-D) magnetic resonance images (MRIs). To formulate the discrete equations of the deformable model, a flexible particle shape function is employed in the Galerkin approximation of the weak form of the equilibrium equations. The proposed support generation method ensures that support of all particles cover the entire computational domains. The deformable model is adaptively adjusted by dilating the shape function and by inserting or merging particles in the high curvature regions or regions stopped by the target boundary. The shape function of the particle with a dilation parameter is adaptively constructed in response to particle insertion or merging. The proposed method offers flexibility in representing highly convolved structures and in refining the deformable models. Self-intersection of the surface, during evolution, is prevented by tracing backward along gradient descent direction from the crest interface of the distance field, which is computed by fast marching. These operations involve a significant computational cost. The initial model for the deformable surface is simple and requires no prior knowledge of the segmented structure. No specific template is required, e.g., an average cortical surface obtained from many subjects. The extracted cortical surface efficiently localizes the depths of the cerebral sulci, unlike some other active surface approaches that penalize regions of high curvature. Comparisons with manually segmented landmark data are provided to demonstrate the high accuracy of the proposed method. We also compare the proposed method to the finite element method, and to a commonly used cortical surface extraction approach, the CRUISE method. We also show that the independence of the shape functions of the RKPM from the underlying mesh enhances the convergence speed of the deformable model.

Level set methods offer highly robust and accurate methods for detecting interfaces of complex structures. Efficient techniques are required to transform an interface to a globally defined level set function. In this paper, a novel level set method based on an adaptive triangular mesh is proposed for segmentation of medical images. Special attention is paid to an adaptive mesh refinement and redistancing technique for level set propagation, in order to achieve higher resolution at the interface with minimum expense. First, a narrow band around the interface is built in an upwind fashion. An active square technique is used to determine the shortest distance correspondence (SDC) for each grid vertex. Simultaneously, we also give an efficient approach for signing the distance field. Then, an adaptive improvement algorithm is proposed, which essentially combines two basic techniques: a long-edge-based vertex insertion strategy, and a local improvement. These guarantee that the refined triangulation is related to features along the front and has elements with appropriate size and shape, which fit the front well. We propose a short-edge elimination scheme to coarsen the refined triangular mesh, in order to reduce the extra storage. Finally, we reformulate the general evolution equation by updating 1) the velocities and 2) the gradient of level sets on the triangulated mesh. We give an approach for tracing contours from the level set on the triangulated mesh. Given a two-dimensional image with N grids along a side, the proposed algorithms run in O(kN) time at each iteration. Quantitative analysis shows that our algorithm is of first order accuracy; and when the interface-fitted property is involved in the mesh refinement, both the convergence speed and numerical accuracy are greatly improved. We also analyze the effect of redistancing frequency upon convergence speed and accuracy. Numerical examples include the extraction of inner and outer surfaces of the cerebral cortex from magnetic resonance imaging brain images.

In the field of template-based medical image analysis, image registration and normalization are frequently used to evaluate and interpret data in a standard template or reference atlas space. Despite the large number of image-registration (warping) techniques developed recently in the literature, only a few studies have been undertaken to numerically characterize and compare various alignment methods. In this paper, we introduce a new approach for analyzing image registration based on a selective-wavelet reconstruction technique using a frequency-adaptive wavelet shrinkage. We study four polynomial-based and two higher complexity nonaffine warping methods applied to groups of stereotaxic human brain structural (magnetic resonance imaging) and functional (positron emission tomography) data. Depending upon the aim of the image registration, we present several warp classification schemes. Our method uses a concise representation of the native and resliced (pre- and post-warp) data in compressed wavelet space to assess quality of registration. This technique is computationally inexpensive and utilizes the image compression, image enhancement, and denoising characteristics of the wavelet-based function representation, as well as the optimality properties of frequency-dependent wavelet shrinkage.

This paper presents a fully automated segmentation method for medical images. The goal is to localize and parameterize a variety of types of structure in these images for subsequent quantitative analysis. We propose a new hybrid strategy that combines a general elastic template matching approach and an evolutionary heuristic. The evolutionary algorithm uses prior statistical information about the shape of the target structure to control the behavior of a number of deformable templates. Each template, modeled in the form of a B-spline, is warped in a potential field which is itself dynamically adapted. Such a hybrid scheme proves to be promising: by maintaining a population of templates, we cover a large domain of the solution space under the global guidance of the evolutionary heuristic, and thoroughly explore interesting areas. We address key issues of automated image segmentation systems. The potential fields are initially designed based on the spatial features of the edges in the input image, and are subjected to spatially adaptive diffusion to guarantee the deformation of the template. This also improves its global consistency and convergence speed. The deformation algorithm can modify the internal structure of the templates to allow a better match. We investigate in detail the preprocessing phase that the images undergo before they can be used more effectively in the iterative elastic matching procedure: a texture classifier, trained via linear discriminant analysis of a learning set, is used to enhance the contrast of the target structure with respect to surrounding tissues. We show how these techniques interact within a statistically driven evolutionary scheme to achieve a better tradeoff between template flexibility and sensitivity to noise and outliers. We focus on understanding the features of template matching that are most beneficial in terms of the achieved match. Examples from simulated and real image data are discussed, with considerations of algorithmic efficiency.

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype- phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders.

There are a variety of research applications that require reconstruction of objects from unorganized points. In our implementation, we accomplish this task in two steps: first by connecting points to contours and then contours to objects. We focus on the first step in this paper. We present a Voxel-coding algorithm which assembles unorganized points into contours in a straightforward and efficient way. First the points are converted into a binary volumetric object using simple 3D Voxel-coding starting with voxels that include the sample points. Then contours are interpreted as centerlines of cross-sections. The centerlines are obtained by using a series of2D Voxel-coding operations.Input points are sampled from an unknown object satisfying certain sampling criteria. No additional details about the input data are needed. Output contours pass through or approximate sample points. The algorithm is tested with several data sets, showing its efficiency.

This paper discusses voxel-coding for tiling complex volumetric objects with triangular meshes: first choosing cross-sections followed by extracting contours, and then triangulating them according to a given error threshold. The intervals between adjacent cross-sections and for sampling contour points for the tiling operation are determined by the difference in area between contour projections, enabling a relatively small number of triangles to reconstruct the object. Branching problems are solved by introducing a simplified skeleton extracted from the difference region and then finding matched segments of the skeleton for each contour i.e., converting multiple contour connections into a single pair connection. For all major problems involved in reconstruction, voxel-coding provides new and robust solutions. These problems include contour extraction, region filling with arbitrarily complex boundaries for difference region searches, simplified skeleton extraction, contour-skeleton matching, and mapping of curve pairs for contour tiling. The voxel-coding proposed can reconstruct surfaces from complex volumetric objects or contours themselves. The input data may have multiple branches or holes, and is processed in a fully automatic and systematic way. The algorithm is easy to implement, fast to compute and insensitive to abject complexity. This technique is of special importance for bridging discrete volumetric and continuous objects.

Skeletonization promises to become a powerful tool for compact shape description, path planning, and other applications. However, current techniques can seldom efficiently process real, complicated 3D data sets, such as MRI and CT data of human organs. In this paper, we present an efficient voxel-coding based algorithm for Skeletonization of 3D voxelized objects. The skeletons are interpreted as connected centerlines. consisting of sequences of medial points of consecutive clusters. These centerlines are initially extracted as paths of voxels, followed by medial point replacement, refinement, smoothness, and connection operations. The voxel-coding techniques have been proposed for each of these operations in a uniform and systematic fashion. In addition to preserving basic connectivity and centeredness, the algorithm is characterized by straightforward computation, no sensitivity to object boundary complexity, explicit extraction of ready-to-parameterize and branch-controlled skeletons, and efficient object hole detection. These issues are rarely discussed in traditional methods. A range of 3D medical MRI and CT data sets were used for testing the algorithm, demonstrating its utility.

The authors have devised, implemented, and tested a fast, spatially accurate technique for calculating the high-dimensional deformation field relating the brain anatomies of an arbitrary pair of subjects. The resulting three-dimensional (3-D) deformation map can be used to quantify anatomic differences between subjects or within the same subject over time and to transfer functional information between subjects or integrate that information on a single anatomic template. The new procedure is based on developmental processes responsible for variations in normal human anatomy and is applicable to 3-D brain images in general, regardless of modality. Hybrid surface models known as Chen surfaces (based on superquadrics and spherical harmonics) are used to efficiently initialize 3-D active surfaces, and these then extract from both scans the developmentally fundamental surfaces of the ventricles and cortex. The construction of extremely complex surface deformation maps on the internal cortex is made easier by building a generic surface structure to model it. Connected systems of parametric meshes model several deep sulci whose trajectories represent critical functional boundaries. These sulci are sufficiently extended inside the brain to reflect subtle and distributed variations in neuroanatomy between subjects. The algorithm then calculates the high-dimensional volumetric warp (typically with 3842x256x3 approximately 0.1 billion degrees of freedom) deforming one 3-D scan into structural correspondence with the other. Integral distortion functions are used to extend the deformation field required to elastically transform nested surfaces to their counterparts in the target scan. The algorithm's accuracy is tested, by warping 3-D magnetic resonance imaging (MRI) volumes from normal subjects and Alzheimer's patients, and by warping full-color 1024(3 ) digital cryosection volumes of the human head onto MRI volumes. Applications are discussed, including the transfer of multisubject 3-D functional, vascular, and histologic maps onto a single anatomic template; the mapping of 3-D brain atlases onto the scans of new subjects; and the rapid detection, quantification, and mapping of local shape changes in 3-D medical images in disease and during normal or abnormal growth and development.