[show abstract][hide abstract] ABSTRACT: The degree to which one identifies as male or female has a profound impact on one's life. Yet, there is a limited understanding of what contributes to this important characteristic termed gender identity. In order to reveal factors influencing gender identity, studies have focused on people who report strong feelings of being the opposite sex, such as male-to-female (MTF) transsexuals.
To investigate potential neuroanatomical variations associated with transsexualism, we compared the regional thickness of the cerebral cortex between 24 MTF transsexuals who had not yet been treated with cross-sex hormones and 24 age-matched control males.
Results revealed thicker cortices in MTF transsexuals, both within regions of the left hemisphere (i.e., frontal and orbito-frontal cortex, central sulcus, perisylvian regions, paracentral gyrus) and right hemisphere (i.e., pre-/post-central gyrus, parietal cortex, temporal cortex, precuneus, fusiform, lingual, and orbito-frontal gyrus).
These findings provide further evidence that brain anatomy is associated with gender identity, where measures in MTF transsexuals appear to be shifted away from gender-congruent men.
Journal of Behavioral and Brain Science 08/2012; 2(3):357-362.
[show abstract][hide abstract] ABSTRACT: Knowledge of the properties of white matter fiber tracts isa crucial and necessary step toward a precise understanding of the functional architecture of the living human brain. Previously, this knowledge was severely limited, as it was difficult to visualize these structures or measure their functions in vivo. The HCP has recently generated considerable interest because of its potential to explore connectivity and its relationship with genetics and behavior. For neuroscientists and the lay public alike, the ability to assess, measure, and explore this wealth of layered information concerning how the brain is wired is a much sought after prize.The navigation of the human connectome and the discovery of how it is affected through genetics, and in a range of neurological and psychiatric diseases, have far reaching implications. From a range of ongoing connectomics related activities, the systematic characterization of brain connectedness and the resulting functional aspects of such connectivity will not only realize the work of Ramón y Cajal and others, but will also greatly expand our understanding of the brain, the mind, and what it is to be truly human. The similarities and differences that mark normal diversity will help us to understand variation among people and set the stage to chart genetic influences on typical brain development and decline during aging. What is more, an understanding of how brains might become disordered will shed light on autism, schizophrenia, Alzheimer’s, and other diseases that exact a tremendous and terrible social and economic toll.
[show abstract][hide abstract] ABSTRACT: Analyzing geometry of sulcal curves on the human cortical surface requires a shape representation invariant to Euclidean motion. We present a novel shape representation that characterizes the shape of a curve in terms of a coordinate system based on the eigensystem of the anisotropic Helmholtz equation. This representation has many desirable properties: stability, uniqueness and invariance to scaling and isometric transformation. Under this representation, we can find a point-wise shape distance between curves as well as a bijective smooth point-to-point correspondence. When the curves are sampled irregularly, we also present a fast and accurate computational method for solving the eigensystem using a finite element formulation. This shape representation is used to find symmetries between corresponding sulcal shapes between cortical hemispheres. For this purpose, we automatically generate 26 sulcal curves for 24 subject brains and then compute their invariant shape representation. Left-right sulcal shape symmetry as measured by the shape representation's metric demonstrates the utility of the presented invariant representation for shape analysis of the cortical folding pattern.
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention. 01/2012; 15(Pt 3):607-14.
[show abstract][hide abstract] ABSTRACT: Sulcal folds (sulci) on the cortical surface are important landmarks of interest for investigating brain development and disease. Accurate and automatic delineation of the sulci is a challenging problem due to substantial variability in their shapes across populations. We present a geodesic curvature flow method for an automatic and accurate delineation of sulcal curves. We assume as input an atlas brain surface mesh on which a set of sulcal curves have been delineated. The sulcal curves are transferred to approximate corresponding locations on the subject brain using a transformation defined by an automatic surface based registration method. The locations of these curves are then refined to follow the true sulcal fundi more closely using geodesic curvature flow on the cortical surface. We present a level set based formulation of this flow on non-flat surfaces which represents the sulcal curves as zero level sets. We also incorporate a curvature based weighting that drives the sulcal curves to the bottoms of the sulcal valleys in the cortical folds. The resulting PDE is discretized on a triangulated mesh using finite elements. Finally, we present a validation by comparing sets of automatically delineated sul-cal curves with sets of manually delineated sulcal curves and show that the proposed method is able to find them accurately.
Biomedical Imaging (ISBI), 2012 9th IEEE International Symposium on; 01/2012
[show abstract][hide abstract] ABSTRACT: Insight into brain development and organization can be gained by computing correlations between structural and functional measures in parcellated cortex. Partial correlations can often reduce ambiguity in correlation data by identifying those pairs of regions whose similarity cannot be explained by the influence of other regions with which they may both interact. Consequently a graph with edges indicating non-zero partial correlations may reveal important subnetworks obscured in the correlation data. Here we describe and investigate PC∗, a graph pruning algorithm for identification of the partial correlation network in comparison to direct calculation of partial correlations from the inverse of the sample correlation matrix. We show that PC∗ is far more robust and illustrate its use in the study of covariation in cortical thickness in ROIs defined on a parcellated cortex.
Proceedings / IEEE International Symposium on Biomedical Imaging: from nano to macro. IEEE International Symposium on Biomedical Imaging 01/2012;
[show abstract][hide abstract] ABSTRACT: 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.
Journal of the American Medical Informatics Association 11/2011; 19(2):202-6. · 3.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Segmenting brain from non-brain tissue within magnetic resonance (MR) images of the human head, also known as skull-stripping, is a critical processing step in the analysis of neuroimaging data. Though many algorithms have been developed to address this problem, challenges remain. In this paper, we apply the “deformable organism” framework to the skull-stripping problem. Within this framework, deformable models are equipped with higher-level control mechanisms based on the principles of artificial life, including sensing, reactive behavior, knowledge representation, and proactive planning. Our new deformable organisms are governed by a high-level plan aimed at the fully-automated segmentation of various parts of the head in MR imagery, and they are able to cooperate in computing a robust and accurate segmentation. We applied our segmentation approach to a test set of human MRI data using manual delineations of the data as a reference “gold standard.” We compare these results with results from three widely used methods using set-similarity metrics.
Proceedings of the 8th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2011, March 30 - April 2, 2011, Chicago, Illinois, USA; 01/2011
[show abstract][hide abstract] ABSTRACT: For pre-clinical bioluminescence or fluorescence optical tomography, the animal's surface topography and internal anatomy need to be estimated for improving the quantitative accuracy of reconstructed images. The animal's surface profile can be measured by all-optical systems, but estimation of the internal anatomy using optical techniques is non-trivial. A 3D anatomical mouse atlas may be warped to the estimated surface. However, fitting an atlas to surface topography data is challenging because of variations in the posture and morphology of imaged mice. In addition, acquisition of partial data (for example, from limited views or with limited sampling) can make the warping problem ill-conditioned. Here, we present a method for fitting a deformable mouse atlas to surface topographic range data acquired by an optical system. As an initialization procedure, we match the posture of the atlas to the posture of the mouse being imaged using landmark constraints. The asymmetric L(2) pseudo-distance between the atlas surface and the mouse surface is then minimized in order to register two data sets. A Laplacian prior is used to ensure smoothness of the surface warping field. Once the atlas surface is normalized to match the range data, the internal anatomy is transformed using elastic energy minimization. We present results from performance evaluation studies of our method where we have measured the volumetric overlap between the internal organs delineated directly from MRI or CT and those estimated by our proposed warping scheme. Computed Dice coefficients indicate excellent overlap in the brain and the heart, with fair agreement in the kidneys and the bladder.
Physics in Medicine and Biology 09/2010; 55(20):6197-214. · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: A new method for tissue classification of brain magnetic resonance images (MRI) of the brain is proposed. The method is based on local image models where each models the image content in a subset of the image domain. With this local modeling approach, the assumption that tissue types have the same characteristics over the brain needs not to be evoked. This is important because tissue type characteristics, such as T1 and T2 relaxation times and proton density, vary across the individual brain and the proposed method offers improved protection against intensity non-uniformity artifacts that can hamper automatic tissue classification methods in brain MRI. A framework in which local models for tissue intensities and Markov Random Field (MRF) priors are combined into a global probabilistic image model is introduced. This global model will be an inhomogeneous MRF and it can be solved by standard algorithms such as iterative conditional modes. The division of the whole image domain into local brain regions possibly having different intensity statistics is realized via sub-volume probabilistic atlases. Finally, the parameters for the local intensity models are obtained without supervision by maximizing the weighted likelihood of a certain finite mixture model. For the maximization task, a novel genetic algorithm almost free of initialization dependency is applied. The algorithm is tested on both simulated and real brain MR images. The experiments confirm that the new method offers a useful improvement of the tissue classification accuracy when the basic tissue characteristics vary across the brain and the noise level of the images is reasonable. The method also offers better protection against intensity non-uniformity artifact than the corresponding method based on a global (whole image) modeling scheme.
Magnetic Resonance Imaging 05/2010; 28(4):557-73. · 2.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: Flat mapping based cortical surface registration constrained by manually traced sulcal curves has been widely used for inter subject comparisons of neuroanatomical data. Even for an experienced neuroanatomist, manual sulcal tracing can be quite time consuming, with the cost increasing with the number of sulcal curves used for registration. We present a method for estimation of an optimal subset of size N(C) from N possible candidate sulcal curves that minimizes a mean squared error metric over all combinations of N(C) curves. The resulting procedure allows us to estimate a subset with a reduced number of curves to be traced as part of the registration procedure leading to optimal use of manual labeling effort for registration. To minimize the error metric we analyze the correlation structure of the errors in the sulcal curves by modeling them as a multivariate Gaussian distribution. For a given subset of sulci used as constraints in surface registration, the proposed model estimates registration error based on the correlation structure of the sulcal errors. The optimal subset of constraint curves consists of the N(C) sulci that jointly minimize the estimated error variance for the subset of unconstrained curves conditioned on the N(C) constraint curves. The optimal subsets of sulci are presented and the estimated and actual registration errors for these subsets are computed.
[show abstract][hide abstract] ABSTRACT: Methods and tools for visualizing biological data have improved considerably over the last decades, but they are still inadequate for some high-throughput data sets. For most users, a key challenge is to benefit from the deluge of data without being overwhelmed by it. This challenge is still largely unfulfilled and will require the development of truly integrated and highly useable tools.
[show abstract][hide abstract] ABSTRACT: Advances in imaging techniques and high-throughput technologies are providing scientists with unprecedented possibilities to visualize internal structures of cells, organs and organisms and to collect systematic image data characterizing genes and proteins on a large scale. To make the best use of these increasingly complex and large image data resources, the scientific community must be provided with methods to query, analyze and crosslink these resources to give an intuitive visual representation of the data. This review gives an overview of existing methods and tools for this purpose and highlights some of their limitations and challenges.
[show abstract][hide abstract] ABSTRACT: Brain connectivity patterns are useful in understanding brain function and organization. Anatomical brain connectivity is largely determined using the physical synaptic connections between neurons. In contrast statistical brain connectivity in a given brain population refers to the interaction and interdependencies of statistics of multitudes of brain features including cortical area, volume, thickness etc. Traditionally, this dependence has been studied by statistical correlations of cortical features. In this paper, we propose the use of Bayesian network modeling for inferring statistical brain connectivity patterns that relate to causal (directed) as well as non-causal (undirected) relationships between cortical surface areas. We argue that for multivariate cortical data, the Bayesian model provides for a more accurate representation by removing the effect of confounding correlations that get introduced due to canonical dependence between the data. Results are presented for a population of 466 brains, where a SEM (structural equation modeling) approach is used to generate a Bayesian network model, as well as a dependency graph for the joint distribution of cortical areas.
[show abstract][hide abstract] ABSTRACT: Group analysis of structure or function in cerebral cortex typically involves, as a first step, the alignment of cortices. A surface-based approach to this problem treats the cortex as a convoluted surface and coregisters across subjects so that cortical landmarks or features are aligned. This registration can be performed using curves representing sulcal fundi and gyral crowns to constrain the mapping. Alternatively, registration can be based on the alignment of curvature metrics computed over the entire cortical surface. The former approach typically involves some degree of user interaction in defining the sulcal and gyral landmarks while the latter methods can be completely automated. Here we introduce a cortical delineation protocol consisting of 26 consistent landmarks spanning the entire cortical surface. We then compare the performance of a landmark-based registration method that uses this protocol with that of two automatic methods implemented in the software packages FreeSurfer and BrainVoyager. We compare performance in terms of discrepancy maps between the different methods, the accuracy with which regions of interest are aligned, and the ability of the automated methods to correctly align standard cortical landmarks. Our results show similar performance for ROIs in the perisylvian region for the landmark-based method and FreeSurfer. However, the discrepancy maps showed larger variability between methods in occipital and frontal cortex and automated methods often produce misalignment of standard cortical landmarks. Consequently, selection of the registration approach should consider the importance of accurate sulcal alignment for the specific task for which coregistration is being performed. When automatic methods are used, the users should ensure that sulci in regions of interest in their studies are adequately aligned before proceeding with subsequent analysis.
[show abstract][hide abstract] ABSTRACT: Structural connectivity in human brain has been studied by modeling the statistical dependence between features of cortical regions, such as gray matter thickness. Statistical correlations between gray matter thickness have been mainly used as a metric to study this dependence. In this paper, we propose the use of partial correlations instead of Pearson correlation for inferring the brain structural connectivity using gray matter volumes from a large population of 466 subjects. We argue that partial-correlation is a better measure for extracting connectivity matrix from multivariate data because it removes the effects of confounding correlations that get introduced due to canonical dependence between data. Our experimental results on gray-matter volumes from a large population of brains compare and contrast the connectivities obtained by applying both correlation and partial correlation analysis.
Biomedical Imaging: From Nano to Macro, 2010 IEEE International Symposium on; 01/2010
[show abstract][hide abstract] ABSTRACT: Estimation of internal mouse anatomy is required for quantitative bioluminescence or fluorescence tomography. However, only surface range data can be recovered from all-optical systems. These data are at times sparse or incomplete. We present a method for fitting an elastically deformable mouse atlas to surface topographic range data acquired by an optical system. In this method, we first match the postures of a deformable atlas and the range data of the mouse being imaged. This is achieved by aligning manually identified landmarks. We then minimize the asymmetric L(2) pseudo-distance between the surface of the deformable atlas and the surface topography range data. Once this registration is accomplished, the internal anatomy of the atlas is transformed to the coordinate system of the range data using elastic energy minimization. We evaluated our method by using it to register a digital mouse atlas to a surface model produced from a manually labeled CT mouse data set. Dice coefficents indicated excellent agreement in the brain and heart, with fair agreement in the kidneys and bladder. We also present example results produced using our method to align the digital mouse atlas to surface range data.
Proceedings / IEEE International Symposium on Biomedical Imaging: from nano to macro. IEEE International Symposium on Biomedical Imaging 08/2009; 2009:366-369.
[show abstract][hide abstract] ABSTRACT: We introduce a fluid mechanics based tractography method that estimates the most likely connection path between points in a tensor distribution function (TDF) dataset. We simulated the flow of an artificial fluid whose properties are related to the underlying TDF dataset. The resulting fluid velocity was used as a metric of connection strength. We validated our algorithm using a digital phantom dataset based on a pattern with two intersecting tracts. When compared to a TDF streamline method and our single tensor fluid mechanics tractography algorithm, our method was able to segment intersecting tracts at a finer spatial resolution. Our method was successfully applied to human control data to segment a major fiber pathway, the corpus callosum, even in problematic regions with crossing fiber geometries.
Biomedical Imaging: From Nano to Macro, 2009. ISBI '09. IEEE International Symposium on; 08/2009
[show abstract][hide abstract] ABSTRACT: Neuroimaging data, such as 3-D maps of cortical thickness or neural activation, can often be analyzed more informatively with respect to the cortical surface rather than the entire volume of the brain. Any cortical surface-based analysis should be carried out using computations in the intrinsic geometry of the surface rather than using the metric of the ambient 3-D space. We present parameterization-based numerical methods for performing isotropic and anisotropic filtering on triangulated surface geometries. In contrast to existing FEM-based methods for triangulated geometries, our approach accounts for the metric of the surface. In order to discretize and numerically compute the isotropic and anisotropic geometric operators, we first parameterize the surface using a p-harmonic mapping. We then use this parameterization as our computational domain and account for the surface metric while carrying out isotropic and anisotropic filtering. To validate our method, we compare our numerical results to the analytical expression for isotropic diffusion on a spherical surface. We apply these methods to smoothing of mean curvature maps on the cortical surface, a step commonly required for analysis of gyrification or for registering surface-based maps across subjects.
[show abstract][hide abstract] ABSTRACT: Manually labeled landmark sets are often required as inputs for landmark-based image registration. Identifying an optimal subset of landmarks from a training dataset may be useful in reducing the labor intensive task of manual labeling. In this paper, we present a new problem and a method to solve it: given a set of N landmarks, find the k(< N) best landmarks such that aligning these k landmarks that produce the best overall alignment of all N landmarks. The resulting procedure allows us to select a reduced number of landmarks to be labeled as a part of the registration procedure. We apply this methodology to the problem of registering cerebral cortical surfaces extracted from MRI data. We use manually traced sulcal curves as landmarks in performing inter-subject registration of these surfaces. To minimize the error metric, we analyze the correlation structure of the sulcal errors in the landmark points by modeling them as a multivariate Gaussian process. Selection of the optimal subset of sulcal curves is performed by computing the error variance for the subset of unconstrained landmarks conditioned on the constrained set. We show that the registration error predicted by our method closely matches the actual registration error. The method determines optimal curve subsets of any given size with minimal registration error.
Proceedings / CVPR, IEEE Computer Society Conference on Computer Vision and Pattern Recognition. IEEE Computer Society Conference on Computer Vision and Pattern Recognition 06/2009; 20-25:699-706.
[show abstract][hide abstract] ABSTRACT: 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.
IEEE transactions on medical imaging. 04/2009; 28(3):348-60.