Publications

2013
Kolesov I, Lee J, Vela P, Tannenbaum A. Stochastic Image Registration with User Constraints. Proc SPIE Int Soc Opt Eng. 2013;8669.Abstract
Constrained registration is an active area of research and is the focus of this work. This note describes a non-rigid image registration framework for incorporating landmark constraints. Points that must remain stationary are selected, the user chooses the spatial extent of the inputs, and an automatic step computes the deformable registration, respecting the constraints. Parametrization of the deformation field is by an additive composition of a similarity transformation and a set of Gaussian radial basis functions. The bases' centers, variances, and weights are determined with a global optimization approach that is introduced. This approach is based on the particle filter for performing constrained optimization; it explores a series of states defining a deformation field that is physically meaningful (i.e., invertible) and prevents chosen points from moving. Results on synthetic two dimensional images are presented.
Wachinger C, Sharp GC, Golland P. Contour-Driven Regression for Label Inference in Atlas-Based Segmentation. Med Image Comput Comput Assist Interv. 2013;16 (Pt 3) :211-8.Abstract
We present a novel method for inferring tissue labels in atlas-based image segmentation using Gaussian process regression. Atlas-based segmentation results in probabilistic label maps that serve as input to our method. We introduce a contour-driven prior distribution over label maps to incorporate image features of the input scan into the label inference problem. The mean function of the Gaussian process posterior distribution yields the MAP estimate of the label map and is used in the subsequent voting. We demonstrate improved segmentation accuracy when our approach is combined with two different patch-based segmentation techniques. We focus on the segmentation of parotid glands in CT scans of patients with head and neck cancer, which is important for radiation therapy planning.
Rathi Y, Gagoski B, Setsompop K, Michailovich O, Grant EP, Westin C-F. Diffusion Propagator Estimation from Sparse Measurements in a Tractography Framework. Med Image Comput Comput Assist Interv. 2013;16 (Pt 3) :510-7.Abstract
Estimation of the diffusion propagator from a sparse set of diffusion MRI (dMRI) measurements is a field of active research. Sparse reconstruction methods propose to reduce scan time and are particularly suitable for scanning un-coperative patients. Recent work on reconstructing the diffusion signal from very few measurements using compressed sensing based techniques has focussed on propagator (or signal) estimation at each voxel independently. However, the goal of many neuroscience studies is to use tractography to study the pathology in white matter fiber tracts. Thus, in this work, we propose a joint framework for robust estimation of the diffusion propagator from sparse measurements while simultaneously tracing the white matter tracts. We propose to use a novel multi-tensor model of diffusion which incorporates the biexponential radial decay of the signal. Our preliminary results on in-vivo data show that the proposed method produces consistent and reliable fiber tracts from very few gradient directions while simultaneously estimating the bi-exponential decay of the diffusion propagator.
Liu S, Song Y, Cai W, Pujol S, Kikinis R, Wang X, Feng D. Multifold Bayesian Kernelization in Alzheimer's Diagnosis. Med Image Comput Comput Assist Interv. 2013;16 (Pt 2) :303-10.Abstract
The accurate diagnosis of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) is important in early dementia detection and treatment planning. Most of current studies formulate the AD diagnosis scenario as a classification problem and solve it using various machine learners trained with multi-modal biomarkers. However, the diagnosis accuracy is usually constrained by the performance of the machine learners as well as the methods of integrating the multi-modal data. In this study, we propose a novel diagnosis algorithm, the Multifold Bayesian Kernelization (MBK), which models the diagnosis process as a synthesis analysis of multi-modal biomarkers. MBK constructs a kernel for each biomarker that maximizes the local neighborhood affinity, and further evaluates the contribution of each biomarker based on a Bayesian framework. MBK adopts a novel diagnosis scheme that could infer the subject's diagnosis by synthesizing the output diagnosis probabilities of individual biomarkers. The proposed algorithm, validated using multimodal neuroimaging data from the ADNI baseline cohort with 85 AD, 169 MCI and 77 cognitive normal subjects, achieves significant improvements on all diagnosis groups compared to the state-of-the-art methods.
Knutsson H, Westin C-F. Tensor Metrics and Charged Containers for 3D Q-space Sample Distribution. Med Image Comput Comput Assist Interv. 2013;16 (Pt 1) :679-86.Abstract
This paper extends Jones' popular electrostatic repulsion based algorithm for distribution of single-shell Q-space samples in two fundamental ways. The first alleviates the single-shell requirement enabling full Q-space sampling. Such an extension is not immediately obvious since it requires distributing samples evenly in 3 dimensions. The extension is as elegant as it is simple: Add a container volume of the desired shape having a constant charge density and a total charge equal to the negative of the sum of the moving point charges. Results for spherical and cubic charge containers are given. The second extension concerns the way distances between sample point are measured. The Q-space samples represent orientation, rather than direction and it would seem appropriate to use a metric that reflects this fact, e.g. a tensor metric. To this end we present a means to employ a generalized metric in the optimization. Minimizing the energy will result in a 3-dimensional distribution of point charges that is uniform in the terms of the specified metric. The radically different distributions generated using different metrics pinpoints a fundamental question: Is there an inherent optimal metric for Q-space sampling? Our work provides a versatile tool to explore the role of different metrics and we believe it will be an important contribution to further the continuing debate and research on the matter.
Toews M, Wells III WM. Efficient and Robust Model-to-image Alignment using 3D Scale-invariant Features. Med Image Anal. 2013;17 (3) :271-82.Abstract

This paper presents feature-based alignment (FBA), a general method for efficient and robust model-to-image alignment. Volumetric images, e.g. CT scans of the human body, are modeled probabilistically as a collage of 3D scale-invariant image features within a normalized reference space. Features are incorporated as a latent random variable and marginalized out in computing a maximum a posteriori alignment solution. The model is learned from features extracted in pre-aligned training images, then fit to features extracted from a new image to identify a globally optimal locally linear alignment solution. Novel techniques are presented for determining local feature orientation and efficiently encoding feature intensity in 3D. Experiments involving difficult magnetic resonance (MR) images of the human brain demonstrate FBA achieves alignment accuracy similar to widely-used registration methods, while requiring a fraction of the memory and computation resources and offering a more robust, globally optimal solution. Experiments on CT human body scans demonstrate FBA as an effective system for automatic human body alignment where other alignment methods break down.

Lemaire J-J, Golby A, Wells III WM, Pujol S, Tie Y, Rigolo L, Yarmarkovich A, Pieper S, Westin C-F, Jolesz FA, et al. Extended Broca's Area in the Functional Connectome of Language in Adults: Combined Cortical and Subcortical Single-subject Analysis using fMRI and DTI Tractography. Brain Topogr. 2013;26 (3) :428-41.Abstract

Traditional models of the human language circuitry encompass three cortical areas, Broca's, Geschwind's and Wernicke's, and their connectivity through white matter fascicles. The neural connectivity deep to these cortical areas remains poorly understood, as does the macroscopic functional organization of the cortico-subcortical language circuitry. In an effort to expand current knowledge, we combined functional MRI (fMRI) and diffusion tensor imaging to explore subject-specific structural and functional macroscopic connectivity, focusing on Broca's area. Fascicles were studied using diffusion tensor imaging fiber tracking seeded from volumes placed manually within the white matter. White matter fascicles and fMRI-derived clusters (antonym-generation task) of positive and negative blood-oxygen-level-dependent (BOLD) signal were co-registered with 3-D renderings of the brain in 12 healthy subjects. Fascicles connecting BOLD-derived clusters were analyzed within specific cortical areas: Broca's, with the pars triangularis, the pars opercularis, and the pars orbitaris; Geschwind's and Wernicke's; the premotor cortex, the dorsal supplementary motor area, the middle temporal gyrus, the dorsal prefrontal cortex and the frontopolar region. We found a functional connectome divisible into three systems-anterior, superior and inferior-around the insula, more complex than previously thought, particularly with respect to a new extended Broca's area. The extended Broca's area involves two new fascicles: the operculo-premotor fascicle comprised of well-organized U-shaped fibers that connect the pars opercularis with the premotor region; and (2) the triangulo-orbitaris system comprised of intermingled U-shaped fibers that connect the pars triangularis with the pars orbitaris. The findings enhance our understanding of language function.

Venkataraman A, Kubicki M, Golland P. From Connectivity Models to Region Labels: Identifying Foci of a Neurological Disorder. IEEE Trans Med Imaging. 2013;32 (11) :2078-98.Abstract

We propose a novel approach to identify the foci of a neurological disorder based on anatomical and functional connectivity information. Specifically, we formulate a generative model that characterizes the network of abnormal functional connectivity emanating from the affected foci. This allows us to aggregate pairwise connectivity changes into a region-based representation of the disease. We employ the variational expectation-maximization algorithm to fit the model and subsequently identify both the afflicted regions and the differences in connectivity induced by the disorder. We demonstrate our method on a population study of schizophrenia.

Janoos F, Brown G, Mórocz IA, Wells III WM. State-space Analysis of Working Memory in Schizophrenia: An fBIRN Study. Psychometrika. 2013;78 (2) :279-307.Abstract

The neural correlates of working memory (WM) in schizophrenia (SZ) have been extensively studied using the multisite fMRI data acquired by the Functional Biomedical Informatics Research Network (fBIRN) consortium. Although univariate and multivariate analysis methods have been variously employed to localize brain responses under differing task conditions, important hypotheses regarding the representation of mental processes in the spatio-temporal patterns of neural recruitment and the differential organization of these mental processes in patients versus controls have not been addressed in this context. This paper uses a multivariate state-space model (SSM) to analyze the differential representation and organization of mental processes of controls and patients performing the Sternberg Item Recognition Paradigm (SIRP) WM task. The SSM is able to not only predict the mental state of the subject from the data, but also yield estimates of the spatial distribution and temporal ordering of neural activity, along with estimates of the hemodynamic response. The dynamical Bayesian modeling approach used in this study was able to find significant differences between the predictability and organization of the working memory processes of SZ patients versus healthy subjects. Prediction of some stimulus types from imaging data in the SZ group was significantly lower than controls, reflecting a greater level of disorganization/heterogeneity of their mental processes. Moreover, the changes in accuracy of predicting the mental state of the subject with respect to parametric modulations, such as memory load and task duration, may have important implications on the neurocognitive models for WM processes in both SZ and healthy adults. Additionally, the SSM was used to compare the spatio-temporal patterns of mental activity across subjects, in a holistic fashion and to derive a low-dimensional representation space for the SIRP task, in which subjects were found to cluster according to their diagnosis.

2012
Toews M, Wells III WM. Source Code for the Paper Titled: Efficient and Robust Model-to-Image Alignment using 3D Scale-Invariant Features. 2012.Abstract
This paper presents feature-based alignment (FBA), a general method for efficient and robust model-to-image alignment. Volumetric images, e.g. CT scans of the human body, are modeled probabilistically as a collage of 3D scale-invariant image features within a normalized reference space. Features are incorporated as a latent random variable and marginalized out in computing a maximum a-posteriori alignment solution. The model is learned from features extracted in pre-aligned training images, then fit to features extracted from a new image to identify a globally optimal locally linear alignment solution. Novel techniques are presented for determining local feature orientation and efficiently encoding feature intensity in 3D. Experiments involving difficult magnetic resonance (MR) images of the human brain demonstrate FBA achieves alignment accuracy similar to widely-used registration methods, while requiring a fraction of the memory and computation resources and offering a more robust, globally optimal solution. Experiments on CT human body scans demonstrate FBA as an effective system for automatic human body alignment where other alignment methods break down.
Toews featExtract1.4
Shackleford JA, Shusharina N, Verberg J, Warmerdam G, Winey B, Neuner M, Steininger P, Arbisser A, Golland P. Plastimatch 1.6 - Current Capabilities and Future Directions. Int Conf Med Image Comput Comput Assist Interv. Workshop on Image-Guidance and Multimodal Dose Planning in Radiation Therapy. 2012;15 (WS).Abstract
Open-source software provides an economic benefit by reducing duplicated development effort, and advances science knowledge by fostering a culture of reproducible experimentation. This paper describes recent advances in the Plastimatch open software suite, which implements a broad set of useful tools for research and practice in radiotherapy and medical imaging. The focus of this paper is to highlight recent advancements, including 2D-3D registration, GPU-accelerated mutual information, analytic regularization of B-spline registration, automatic 3D feature detection and feature matching, and radiotherapy plan evaluation tools.
Shackleford MICCAI WS 2012
Janoos F, Lee W, Subrahmanya N, Mórocz IA, Wells III WM. Identification of Recurrent Patterns in the Activation of Brain Networks. Adv. In Neural Info. Proc. Sys (NIPS). 2012 :1-9.Abstract
Identifying patterns from the neuroimaging recordings of brain activity related to the unobservable psychological or mental state of an individual can be treated as a unsupervised pattern recognition problem. The main challenges, however, for such an analysis of fMRI data are: a) defining a physiologically meaningful feature-space for representing the spatial patterns across time; b) dealing with the high-dimensionality of the data; and c) robustness to the various artifacts and confounds in the fMRI time-series. In this paper, we present a network-aware feature-space to represent the states of a general network, that enables comparing and clustering such states in a manner that is a) meaningful in terms of the network connectivity structure; b)computationally efficient; c) low-dimensional; and d) relatively robust to structured and random noise artifacts. This feature-space is obtained from a spherical relaxation of the transportation distance metric which measures the cost of trans- porting “mass” over the network to transform one function into another. Through theoretical and empirical assessments, we demonstrate the accuracy and efficiency of the approximation, especially for large problems.
Janoos NIPS 2012
De Bonet J, Zöllei L, Learned-Miller EG, Jakab M, Egger J, Wells III WM. Congealing - A Framework for Aligning Pediatric Brain Images. 2012.Abstract
This software framework brings a set of input volumes from pediatric brains into alignment. Therefore, the notion of pair-wise image registration is extended to group-wise alignment, which allows to find correspondence among a whole group of data sets instead of just two of them. Moreover, it simultaneously brings the set of input volumes into alignment, with every member of the population approaching the group's central tendency at the same time. 
deBonet-Congealing-Framework.zip
Kapur T, Jolesz FA, Lewin JS, Kahn T. Proceedings of the 9th Interventional MRI Symposium. 9th Interventional MRI Symposium. 2012;9 :1-156. 2012 iMRI Symposium Proceedings
Kapur T, Tempany CM, Jolesz FA. Proceedings of the 5th Image Guided Therapy Workshop. Image Guided Therapy Workshop. 2012;5 :1-70. 2012 IGT Workshop Proceedings
Vul E, Lashkari D, Hsieh P-J, Golland P, Kanwisher N. Data-driven Functional Clustering Reveals Dominance of Face, Place, and Body Selectivity in the Ventral Visual Pathway. J Neurophysiol. 2012;108 (8) :2306-22.Abstract
Regions selective for faces, places, and bodies feature prominently in the literature on the human ventral visual pathway. Are selectivities for these categories in fact the most robust response profiles in this pathway, or is their prominence an artifact of biased sampling of the hypothesis space in prior work? Here we use a data-driven structure discovery method that avoids the assumptions built into most prior work by 1) giving equal consideration to all possible response profiles over the conditions tested, 2) relaxing implicit anatomical constraints (that important functional profiles should manifest themselves in spatially contiguous voxels arising in similar locations across subjects), and 3) testing for dominant response profiles over images, rather than categories, thus enabling us to discover, rather than presume, the categories respected by the brain. Even with these assumptions relaxed, face, place, and body selectivity emerge as dominant in the ventral stream.
Irimia A, Wang B, Aylward SR, Prastawa MW, Pace DF, Gerig G, Hovda DA, Kikinis R, Vespa PM, Van Horn JD. Neuroimaging of Structural Pathology and Connectomics in Traumatic Brain Injury: Toward Personalized Outcome Prediction. Neuroimage Clin. 2012;1 (1) :1-17.Abstract
Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome.
Steinert-Threlkeld S, Ardekani S, Mejino JLV, Detwiler LT, Brinkley JF, Halle M, Kikinis R, Winslow RL, Miller MI, Ratnanather TJ. Ontological Labels for Automated Location of Anatomical Shape Differences. J Biomed Inform. 2012;45 (3) :522-7.Abstract

A method for automated location of shape differences in diseased anatomical structures via high resolution biomedical atlases annotated with labels from formal ontologies is described. In particular, a high resolution magnetic resonance image of the myocardium of the human left ventricle was segmented and annotated with structural terms from an extracted subset of the Foundational Model of Anatomy ontology. The atlas was registered to the end systole template of a previous study of left ventricular remodeling in cardiomyopathy using a diffeomorphic registration algorithm. The previous study used thresholding and visual inspection to locate a region of statistical significance which distinguished patients with ischemic cardiomyopathy from those with nonischemic cardiomyopathy. Using semantic technologies and the deformed annotated atlas, this location was more precisely found. Although this study used only a cardiac atlas, it provides a proof-of-concept that ontologically labeled biomedical atlases of any anatomical structure can be used to automate location-based inferences.

Moscufo N, Wolfson L, Meier D, Liguori M, Hildenbrand PG, Wakefield D, Schmidt JA, Pearlson GD, Guttmann CRG. Mobility decline in the elderly relates to lesion accrual in the splenium of the corpus callosum. Age (Dordr). 2012;34 (2) :405-14.Abstract
In a previous cross-sectional study on baseline data, we demonstrated that the volume of brain white matter hyperintensities (WMH) in the splenium of corpus callosum (SCC) predicted the current mobility function of older persons. The primary aim of this follow-up study was to determine the relation of WMH volume change in SCC (SCC-∆WMH) with change in mobility measures. A secondary aim was to characterize the global and regional progression of WMH. Mobility function and WMH burden were evaluated at baseline and at 2 years in 77 community-dwelling individuals (baseline age, 82 ± 4). Regional WMH in SCC, as well as genu and body of corpus callosum, subregions of corona radiata, and superior longitudinal fasciculus were determined using a white matter parcellation atlas. The total WMH volume increased 3.3 ± 3.5 ml/year, mainly through enlargement. Significant WMH increases were observed in all selected regions, particularly within the corona radiata. While at baseline and follow-up we observed correlations between WMH burden and several measures of mobility, longitudinal change correlated only with change in chair rise (CR). SCC-∆WMH showed the highest correlation (r = -0.413, p = 0.0002) and was the best regional predictor of CR decline (OR = 1.5, r(2) = 0.3). The SCC-∆WMH was more than five times larger in the CR-decline group compared to the no-decline group (p = 0.0003). The SCC-∆WMH (top quartile) showed a higher sensitivity/specificity for CR decline compared to change in total WMH, 63/88% versus 52/84%, respectively. The findings suggest that accrual of WMHs in posterior areas of the brain supporting inter-hemispheric integration and processing of visual-spatial information is a mechanism contributing to age-related mobility deterioration.
Gadde S, Aucoin N, Grethe JS, Keator DB, Marcus DS, Pieper S. XCEDE: an extensible schema for biomedical data. Neuroinformatics. 2012;10 (1) :19-32.Abstract
The XCEDE (XML-based Clinical and Experimental Data Exchange) XML schema, developed by members of the BIRN (Biomedical Informatics Research Network), provides an extensive metadata hierarchy for storing, describing and documenting the data generated by scientific studies. Currently at version 2.0, the XCEDE schema serves as a specification for the exchange of scientific data between databases, analysis tools, and web services. It provides a structured metadata hierarchy, storing information relevant to various aspects of an experiment (project, subject, protocol, etc.). Each hierarchy level also provides for the storage of data provenance information allowing for a traceable record of processing and/or changes to the underlying data. The schema is extensible to support the needs of various data modalities and to express types of data not originally envisioned by the developers. The latest version of the XCEDE schema and manual are available from http://www.xcede.org/ .

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