Venkataraman A, Kubicki M, Westin C-F, Golland P. Robust Feature Selection in Resting-State fMRI Connectivity Based on Population Studies. Conf Comput Vis Pattern Recognit Workshops. 2010 :63-70.Abstract
We propose an alternative to univariate statistics for identifying population differences in functional connectivity. Our feature selection method is based on a procedure that searches across subsets of the data to isolate a set of robust, predictive functional connections. The metric, known as the Gini Importance, also summarizes multivariate patterns of interaction, which cannot be captured by univariate techniques. We compare the Gini Importance with univariate statistical tests to evaluate functional connectivity changes induced by schizophrenia. Our empirical results indicate that univariate features vary dramatically across subsets of the data and have little classification power. In contrast, relevant features based on Gini Importance are considerably more stable and allow us to accurately predict the diagnosis of a test subject.
Rathi Y, Malcolm J, Bouix S, Tannenbaum A, Shenton ME. Affine Registration of label maps in Label Space. J Comput. 2010;2 (4) :1-11.Abstract
Two key aspects of coupled multi-object shape analysis and atlas generation are the choice of representation and subsequent registration methods used to align the sample set. For example, a typical brain image can be labeled into three structures: grey matter, white matter and cerebrospinal fluid. Many manipulations such as interpolation, transformation, smoothing, or registration need to be performed on these images before they can be used in further analysis. Current techniques for such analysis tend to trade off performance between the two tasks, performing well for one task but developing problems when used for the other. This article proposes to use a representation that is both flexible and well suited for both tasks. We propose to map object labels to vertices of a regular simplex, e.g . the unit interval for two labels, a triangle for three labels, a tetrahedron for four labels, etc. This representation, which is routinely used in fuzzy classification, is ideally suited for representing and registering multiple shapes. On closer examination, this representation reveals several desirable properties: algebraic operations may be done directly, label uncertainty is expressed as a weighted mixture of labels (probabilistic interpretation), interpolation is unbiased toward any label or the background, and registration may be performed directly. We demonstrate these properties by using label space in a gradient descent based registration scheme to obtain a probabilistic atlas. While straightforward, this iterative method is very slow, could get stuck in local minima, and depends heavily on the initial conditions. To address these issues, two fast methods are proposed which serve as coarse registration schemes following which the iterative descent method can be used to refine the results. Further, we derive an analytical formulation for direct computation of the "group mean" from the parameters of pairwise registration of all the images in the sample set. We show results on richly labeled 2D and 3D data sets.
Scully M, Anderson B, Lane T, Gasparovic C, Magnotta V, Sibbitt W, Roldan C, Kikinis R, Bockholt HJ. An Automated Method for Segmenting White Matter Lesions through Multi-Level Morphometric Feature Classification with Application to Lupus. Front Hum Neurosci. 2010;4 :27.Abstract
We demonstrate an automated, multi-level method to segment white matter brain lesions and apply it to lupus. The method makes use of local morphometric features based on multiple MR sequences, including T1-weighted, T2-weighted, and fluid attenuated inversion recovery. After preprocessing, including co-registration, brain extraction, bias correction, and intensity standardization, 49 features are calculated for each brain voxel based on local morphometry. At each level of segmentation a supervised classifier takes advantage of a different subset of the features to conservatively segment lesion voxels, passing on more difficult voxels to the next classifier. This multi-level approach allows for a fast lesion classification method with tunable trade-offs between sensitivity and specificity producing accuracy comparable to a human rater.
Ou W, Wells III WM, Golland P. Combining Spatial Priors and Anatomical Information for fMRI Detection. Med Image Anal. 2010;14 (3) :318-31.Abstract

In this paper, we analyze Markov Random Field (MRF) as a spatial regularizer in fMRI detection. The low signal-to-noise ratio (SNR) in fMRI images presents a serious challenge for detection algorithms, making regularization necessary to achieve good detection accuracy. Gaussian smoothing, traditionally employed to boost SNR, often produces over-smoothed activation maps. Recently, the use of MRF priors has been suggested as an alternative regularization approach. However, solving for an optimal configuration of the MRF is NP-hard in general. In this work, we investigate fast inference algorithms based on the Mean Field approximation in application to MRF priors for fMRI detection. Furthermore, we propose a novel way to incorporate anatomical information into the MRF-based detection framework and into the traditional smoothing methods. Intuitively speaking, the anatomical evidence increases the likelihood of activation in the gray matter and improves spatial coherency of the resulting activation maps within each tissue type. Validation using the receiver operating characteristic (ROC) analysis and the confusion matrix analysis on simulated data illustrates substantial improvement in detection accuracy using the anatomically guided MRF spatial regularizer. We further demonstrate the potential benefits of the proposed method in real fMRI signals of reduced length. The anatomically guided MRF regularizer enables significant reduction of the scan length while maintaining the quality of the resulting activation maps.

Gao Y, Sandhu R, Fichtinger G, Tannenbaum AR. A coupled global registration and segmentation framework with application to magnetic resonance prostate imagery. IEEE Trans Med Imaging. 2010;29 (10) :1781-94.Abstract
Extracting the prostate from magnetic resonance (MR) imagery is a challenging and important task for medical image analysis and surgical planning. We present in this work a unified shape-based framework to extract the prostate from MR prostate imagery. In many cases, shape-based segmentation is a two-part problem. First, one must properly align a set of training shapes such that any variation in shape is not due to pose. Then segmentation can be performed under the constraint of the learnt shape. However, the general registration task of prostate shapes becomes increasingly difficult due to the large variations in pose and shape in the training sets, and is not readily handled through existing techniques. Thus, the contributions of this paper are twofold. We first explicitly address the registration problem by representing the shapes of a training set as point clouds. In doing so, we are able to exploit the more global aspects of registration via a certain particle filtering based scheme. In addition, once the shapes have been registered, a cost functional is designed to incorporate both the local image statistics as well as the learnt shape prior. We provide experimental results, which include several challenging clinical data sets, to highlight the algorithm's capability of robustly handling supine/prone prostate registration and the overall segmentation task.
Jolley M, Stinstra J, Tate J, Pieper S, MacLeod R, Chu L, Wang P, Triedman JK. Finite element modeling of subcutaneous implantable defibrillator electrodes in an adult torso. Heart Rhythm. 2010;7 (5) :692-8.Abstract
BACKGROUND: Total subcutaneous implantable subcutaneous defibrillators are in development, but optimal electrode configurations are not known. OBJECTIVE: We used image-based finite element models (FEM) to predict the myocardial electric field generated during defibrillation shocks (pseudo-DFT) in a wide variety of reported and innovative subcutaneous electrode positions to determine factors affecting optimal lead positions for subcutaneous implantable cardioverter-defibrillators (S-ICD). METHODS: An image-based FEM of an adult man was used to predict pseudo-DFTs across a wide range of technically feasible S-ICD electrode placements. Generator location, lead location, length, geometry and orientation, and spatial relation of electrodes to ventricular mass were systematically varied. Best electrode configurations were determined, and spatial factors contributing to low pseudo-DFTs were identified using regression and general linear models. RESULTS: A total of 122 single-electrode/array configurations and 28 dual-electrode configurations were simulated. Pseudo-DFTs for single-electrode orientations ranged from 0.60 to 16.0 (mean 2.65 +/- 2.48) times that predicted for the base case, an anterior-posterior configuration recently tested clinically. A total of 32 of 150 tested configurations (21%) had pseudo-DFT ratios
Yeo TBT, Sabuncu MR, Vercauteren T, Holt DJ, Amunts K, Zilles K, Golland P, Fischl B. Learning task-optimal registration cost functions for localizing cytoarchitecture and function in the cerebral cortex. IEEE Trans Med Imaging. 2010;29 (7) :1424-41.Abstract
Image registration is typically formulated as an optimization problem with multiple tunable, manually set parameters. We present a principled framework for learning thousands of parameters of registration cost functions, such as a spatially-varying tradeoff between the image dissimilarity and regularization terms. Our approach belongs to the classic machine learning framework of model selection by optimization of cross-validation error. This second layer of optimization of cross-validation error over and above registration selects parameters in the registration cost function that result in good registration as measured by the performance of the specific application in a training data set. Much research effort has been devoted to developing generic registration algorithms, which are then specialized to particular imaging modalities, particular imaging targets and particular postregistration analyses. Our framework allows for a systematic adaptation of generic registration cost functions to specific applications by learning the "free" parameters in the cost functions. Here, we consider the application of localizing underlying cytoarchitecture and functional regions in the cerebral cortex by alignment of cortical folding. Most previous work assumes that perfectly registering the macro-anatomy also perfectly aligns the underlying cortical function even though macro-anatomy does not completely predict brain function. In contrast, we learn 1) optimal weights on different cortical folds or 2) optimal cortical folding template in the generic weighted sum of squared differences dissimilarity measure for the localization task. We demonstrate state-of-the-art localization results in both histological and functional magnetic resonance imaging data sets.
Lashkari D, Sridharan R, Vul E, Hsieh P-J, Kanwisher N, Golland P. Nonparametric Hierarchical Bayesian Model for Functional Brain Parcellation. Conf Comput Vis Pattern Recognit Workshops. 2010 :15-22.Abstract
We develop a method for unsupervised analysis of functional brain images that learns group-level patterns of functional response. Our algorithm is based on a generative model that comprises two main layers. At the lower level, we express the functional brain response to each stimulus as a binary activation variable. At the next level, we define a prior over the sets of activation variables in all subjects. We use a Hierarchical Dirichlet Process as the prior in order to simultaneously learn the patterns of response that are shared across the group, and to estimate the number of these patterns supported by data. Inference based on this model enables automatic discovery and characterization of salient and consistent patterns in functional signals. We apply our method to data from a study that explores the response of the visual cortex to a collection of images. The discovered profiles of activation correspond to selectivity to a number of image categories such as faces, bodies, and scenes. More generally, our results appear superior to the results of alternative data-driven methods in capturing the category structure in the space of stimuli.
Dominitz A, Tannenbaum A. Texture mapping via optimal mass transport. IEEE Trans Vis Comput Graph. 2010;16 (3) :419-33.Abstract
In this paper, we present a novel method for texture mapping of closed surfaces. Our method is based on the technique of optimal mass transport (also known as the "earth-mover's metric"). This is a classical problem that concerns determining the optimal way, in the sense of minimal transportation cost, of moving a pile of soil from one site to another. In our context, the resulting mapping is area preserving and minimizes angle distortion in the optimal mass sense. Indeed, we first begin with an angle-preserving mapping (which may greatly distort area) and then correct it using the mass transport procedure derived via a certain gradient flow. In order to obtain fast convergence to the optimal mapping, we incorporate a multiresolution scheme into our flow. We also use ideas from discrete exterior calculus in our computations.
Etgar L, Nakhmani A, Tannenbaum A, Lifshitz E, Tannenbaum R. Trajectory control of PbSe-gamma-Fe2O3 nanoplatforms under viscous flow and an external magnetic field. Nanotechnology. 2010;21 (17) :175702.Abstract
The flow behavior of nanostructure clusters, consisting of chemically bonded PbSe quantum dots and magnetic gamma-Fe(2)O(3) nanoparticles, has been investigated. The clusters are regarded as model nanoplatforms with multiple functionalities, where the gamma-Fe(2)O(3) magnets serve as transport vehicles, manipulated by an external magnetic field gradient, and the quantum dots act as fluorescence tags within an optical window in the near-infrared regime. The clusters' flow was characterized by visualizing their trajectories within a viscous fluid (mimicking a blood stream), using an optical imaging method, while the trajectory pictures were analyzed by a specially developed processing package. The trajectories were examined under various flow rates, viscosities and applied magnetic field strengths. The results revealed a control of the trajectories even at low magnetic fields (<1 T), validating the use of similar nanoplatforms as active targeting constituents in personalized medicine.
Walter T, Shattuck DW, Baldock R, Bastin ME, Carpenter AE, Duce S, Ellenberg J, Fraser A, Hamilton N, Pieper S, et al. Visualization of image data from cells to organisms. Nat Methods. 2010;7 (3 Suppl) :S26-41.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.
Malcolm JG, Shenton ME, Rathi Y. Filtered multitensor tractography. IEEE Trans Med Imaging. 2010;29 (9) :1664-75.Abstract
We describe a technique that uses tractography to drive the local fiber model estimation. Existing techniques use independent estimation at each voxel so there is no running knowledge of confidence in the estimated model fit. We formulate fiber tracking as recursive estimation: at each step of tracing the fiber, the current estimate is guided by those previous. To do this we perform tractography within a filter framework and use a discrete mixture of Gaussian tensors to model the signal. Starting from a seed point, each fiber is traced to its termination using an unscented Kalman filter to simultaneously fit the local model to the signal and propagate in the most consistent direction. Despite the presence of noise and uncertainty, this provides a causal estimate of the local structure at each point along the fiber. Using two- and three-fiber models we demonstrate in synthetic experiments that this approach significantly improves the angular resolution at crossings and branchings. In vivo experiments confirm the ability to trace through regions known to contain such crossing and branching while providing inherent path regularization.
Sabuncu MR, Yeo TBT, Van Leemput K, Fischl B, Golland P. A generative model for image segmentation based on label fusion. IEEE Trans Med Imaging. 2010;29 (10) :1714-29.Abstract
We propose a nonparametric, probabilistic model for the automatic segmentation of medical images, given a training set of images and corresponding label maps. The resulting inference algorithms rely on pairwise registrations between the test image and individual training images. The training labels are then transferred to the test image and fused to compute the final segmentation of the test subject. Such label fusion methods have been shown to yield accurate segmentation, since the use of multiple registrations captures greater inter-subject anatomical variability and improves robustness against occasional registration failures. To the best of our knowledge, this manuscript presents the first comprehensive probabilistic framework that rigorously motivates label fusion as a segmentation approach. The proposed framework allows us to compare different label fusion algorithms theoretically and practically. In particular, recent label fusion or multiatlas segmentation algorithms are interpreted as special cases of our framework. We conduct two sets of experiments to validate the proposed methods. In the first set of experiments, we use 39 brain MRI scans-with manually segmented white matter, cerebral cortex, ventricles and subcortical structures-to compare different label fusion algorithms and the widely-used FreeSurfer whole-brain segmentation tool. Our results indicate that the proposed framework yields more accurate segmentation than FreeSurfer and previous label fusion algorithms. In a second experiment, we use brain MRI scans of 282 subjects to demonstrate that the proposed segmentation tool is sufficiently sensitive to robustly detect hippocampal volume changes in a study of aging and Alzheimer's Disease.
Dambreville S, Sandhu R, Yezzi A, Tannenbaum A. A Geometric Approach to Joint 2D Region-Based Segmentation and 3D Pose Estimation Using a 3D Shape Prior. SIAM J Imaging Sci. 2010;3 (1) :110-132.Abstract
In this work, we present an approach to jointly segment a rigid object in a two-dimensional (2D) image and estimate its three-dimensional (3D) pose, using the knowledge of a 3D model. We naturally couple the two processes together into a shape optimization problem and minimize a unique energy functional through a variational approach. Our methodology differs from the standard monocular 3D pose estimation algorithms since it does not rely on local image features. Instead, we use global image statistics to drive the pose estimation process. This confers a satisfying level of robustness to noise and initialization for our algorithm and bypasses the need to establish correspondences between image and object features. Moreover, our methodology possesses the typical qualities of region-based active contour techniques with shape priors, such as robustness to occlusions or missing information, without the need to evolve an infinite dimensional curve. Another novelty of the proposed contribution is to use a unique 3D model surface of the object, instead of learning a large collection of 2D shapes to accommodate the diverse aspects that a 3D object can take when imaged by a camera. Experimental results on both synthetic and real images are provided, which highlight the robust performance of the technique in challenging tracking and segmentation applications.
Sandhu R, Dambreville S, Tannenbaum A. Point set registration via particle filtering and stochastic dynamics. IEEE Trans Pattern Anal Mach Intell. 2010;32 (8) :1459-73.Abstract
In this paper, we propose a particle filtering approach for the problem of registering two point sets that differ by a rigid body transformation. Typically, registration algorithms compute the transformation parameters by maximizing a metric given an estimate of the correspondence between points across the two sets of interest. This can be viewed as a posterior estimation problem, in which the corresponding distribution can naturally be estimated using a particle filter. In this work, we treat motion as a local variation in pose parameters obtained by running a few iterations of a certain local optimizer. Employing this idea, we introduce stochastic motion dynamics to widen the narrow band of convergence often found in local optimizer approaches for registration. Thus, the novelty of our method is threefold: First, we employ a particle filtering scheme to drive the point set registration process. Second, we present a local optimizer that is motivated by the correlation measure. Third, we increase the robustness of the registration performance by introducing a dynamic model of uncertainty for the transformation parameters. In contrast with other techniques, our approach requires no annealing schedule, which results in a reduction in computational complexity (with respect to particle size) as well as maintains the temporal coherency of the state (no loss of information). Also unlike some alternative approaches for point set registration, we make no geometric assumptions on the two data sets. Experimental results are provided that demonstrate the robustness of the algorithm to initialization, noise, missing structures, and/or differing point densities in each set, on several challenging 2D and 3D registration scenarios.
Riklin-Raviv T, Van Leemput K, Menze BH, Wells WM, Golland P. Segmentation of image ensembles via latent atlases. Med Image Anal. 2010;14 (5) :654-65.Abstract
Spatial priors, such as probabilistic atlases, play an important role in MRI segmentation. However, the availability of comprehensive, reliable and suitable manual segmentations for atlas construction is limited. We therefore propose a method for joint segmentation of corresponding regions of interest in a collection of aligned images that does not require labeled training data. Instead, a latent atlas, initialized by at most a single manual segmentation, is inferred from the evolving segmentations of the ensemble. The algorithm is based on probabilistic principles but is solved using partial differential equations (PDEs) and energy minimization criteria. We evaluate the method on two datasets, segmenting subcortical and cortical structures in a multi-subject study and extracting brain tumors in a single-subject multi-modal longitudinal experiment. We compare the segmentation results to manual segmentations, when those exist, and to the results of a state-of-the-art atlas-based segmentation method. The quality of the results supports the latent atlas as a promising alternative when existing atlases are not compatible with the images to be segmented.
Rathi Y, Malcolm JG, Michailovich O, Westin C-F, Shenton ME, Bouix S. Tensor kernels for simultaneous fiber model estimation and tractography. Magn Reson Med. 2010;64 (1) :138-48.Abstract
This paper proposes a novel framework for joint orientation distribution function estimation and tractography based on a new class of tensor kernels. Existing techniques estimate the local fiber orientation at each voxel independently so there is no running knowledge of confidence in the measured signal or estimated fiber orientation. In this work, fiber tracking is formulated as recursive estimation: at each step of tracing the fiber, the current estimate of the orientation distribution function is guided by the previous. To do this, second-and higher-order tensor-based kernels are employed. A weighted mixture of these tensor kernels is used for representing crossing and branching fiber structures. While tracing a fiber, the parameters of the mixture model are estimated based on the orientation distribution function at that location and a smoothness term that penalizes deviation from the previous estimate along the fiber direction. This ensures smooth estimation along the direction of propagation of the fiber. In synthetic experiments, using a mixture of two and three components it is shown that this approach improves the angular resolution at crossings. In vivo experiments using two and three components examine the corpus callosum and corticospinal tract and confirm the ability to trace through regions known to contain such crossing and branching.
Sundaram P, Wells WM, Mulkern RV, Bubrick EJ, Bromfield EB, Münch M, Orbach DB. Fast human brain magnetic resonance responses associated with epileptiform spikes. Magn Reson Med. 2010;64 (6) :1728-38.Abstract
Neuronal currents produce local electromagnetic fields that can potentially modulate the phase of the magnetic resonance signal and thus provide a contrast mechanism tightly linked to neuronal activity. Previous work has demonstrated the feasibility of direct MRI of neuronal activity in phantoms and cell culture, but in vivo efforts have yielded inconclusive, conflicting results. The likelihood of detecting and validating such signals can be increased with (i) fast gradient-echo echo-planar imaging, with acquisition rates sufficient to resolve neuronal activity, (ii) subjects with epilepsy, who frequently experience stereotypical electromagnetic discharges between seizures, expressed as brief, localized, high-amplitude spikes (interictal discharges), and (iii) concurrent electroencephalography. This work demonstrates that both MR magnitude and phase show large-amplitude changes concurrent with electroencephalography spikes. We found a temporal derivative relationship between MR phase and scalp electroencephalography, suggesting that the MR phase changes may be tightly linked to local cerebral activity. We refer to this manner of MR acquisition, designed explicitly to track the electroencephalography, as encephalographic MRI (eMRI). Potential extension of this technique into a general purpose functional neuroimaging tool requires further study of the MR signal changes accompanying lower amplitude neuronal activity than those discussed here.
O'Donnell LJ, Westin C-F, Norton I, Whalen S, Rigolo L, Propper R, Golby AJ. The Fiber Laterality Histogram: A New Way to Measure White Matter Asymmetry. Med Image Comput Comput Assist Interv. 2010;13 (Pt 2) :225-32.Abstract
The quantification of brain asymmetries may provide biomarkers for presurgical localization of language function and can improve our understanding of neural structure-function relationships in health and disease. We propose a new method for studying the asymmetry of the white matter tracts in the entire brain, and we apply it to a preliminary study of normal subjects across the handedness spectrum. Methods for quantifying white matter asymmetry using diffusion MRI tractography have thus far been based on comparing numbers of fibers or volumes of a single fiber tract across hemispheres. We propose a generalization of such methods, where the "number of fibers" laterality measurement is extended to the entire brain using a soft fiber comparison metric. We summarize the distribution of fiber laterality indices over the whole brain in a histogram, and we measure properties of the distribution such as its skewness, median, and inter-quartile range. The whole-brain fiber laterality histogram can be measured in an exploratory fashion without hypothesizing asymmetries only in particular structures. We demonstrate an overall difference in white matter asymmetry in consistent- and inconsistent-handers: the skewness of the fiber laterality histogram is significantly different across handedness groups.
Menze BH, Van Leemput K, Lashkari D, Weber M-A, Ayache N, Golland P. A generative model for brain tumor segmentation in multi-modal images. Med Image Comput Comput Assist Interv. 2010;13 (Pt 2) :151-9.Abstract
We introduce a generative probabilistic model for segmentation of tumors in multi-dimensional images. The model allows for different tumor boundaries in each channel, reflecting difference in tumor appearance across modalities. We augment a probabilistic atlas of healthy tissue priors with a latent atlas of the lesion and derive the estimation algorithm to extract tumor boundaries and the latent atlas from the image data. We present experiments on 25 glioma patient data sets, demonstrating significant improvement over the traditional multivariate tumor segmentation.