Publications by Year: 2012

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/ .
Tristán-Vega A, García-Pérez V, Aja-Fernández S, Westin C-F. Efficient and robust nonlocal means denoising of MR data based on salient features matching. Comput Methods Programs Biomed. 2012;105 (2) :131-44.Abstract
The nonlocal means (NLM) filter has become a popular approach for denoising medical images due to its excellent performance. However, its heavy computational load has been an important shortcoming preventing its use. NLM works by averaging pixels in nonlocal vicinities, weighting them depending on their similarity with the pixel of interest. This similarity is assessed based on the squared difference between corresponding pixels inside local patches centered at the locations compared. Our proposal is to reduce the computational load of this comparison by checking only a subset of salient features associated to the pixels, which suffice to estimate the actual difference as computed in the original NLM approach. The speedup achieved with respect to the original implementation is over one order of magnitude, and, when compared to more recent NLM improvements for MRI denoising, our method is nearly twice as fast. At the same time, we evidence from both synthetic and in vivo experiments that computing of appropriate salient features make the estimation of NLM weights more robust to noise. Consequently, we are able to improve the outcomes achieved with recent state of the art techniques for a wide range of realistic Signal-to-Noise ratio scenarios like diffusion MRI. Finally, the statistical characterization of the features computed allows to get rid of some of the heuristics commonly used for parameter tuning.
Venkataraman A, Rathi Y, Kubicki M, Westin C-F, Golland P. Joint modeling of anatomical and functional connectivity for population studies. IEEE Trans Med Imaging. 2012;31 (2) :164-82.Abstract
We propose a novel probabilistic framework to merge information from diffusion weighted imaging tractography and resting-state functional magnetic resonance imaging correlations to identify connectivity patterns in the brain. In particular, we model the interaction between latent anatomical and functional connectivity and present an intuitive extension to population studies. We employ the EM algorithm to estimate the model parameters by maximizing the data likelihood. The method simultaneously infers the templates of latent connectivity for each population and the differences in connectivity between the groups. We demonstrate our method on a schizophrenia study. Our model identifies significant increases in functional connectivity between the parietal/posterior cingulate region and the frontal lobe and reduced functional connectivity between the parietal/posterior cingulate region and the temporal lobe in schizophrenia. We further establish that our model learns predictive differences between the control and clinical populations, and that combining the two modalities yields better results than considering each one in isolation.
Lashkari D, Sridharan R, Vul E, Hsieh P-J, Kanwisher N, Golland P. Search for patterns of functional specificity in the brain: a nonparametric hierarchical Bayesian model for group fMRI data. Neuroimage. 2012;59 (2) :1348-68.Abstract
Functional MRI studies have uncovered a number of brain areas that demonstrate highly specific functional patterns. In the case of visual object recognition, small, focal regions have been characterized with selectivity for visual categories such as human faces. In this paper, we develop an algorithm that automatically learns patterns of functional specificity from fMRI data in a group of subjects. The method does not require spatial alignment of functional images from different subjects. The 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 sets of activation variables in all subjects. We use a Hierarchical Dirichlet Process as the prior in order to learn the patterns of functional specificity shared across the group, which we call functional systems, and estimate the number of these systems. Inference based on our model enables automatic discovery and characterization of dominant and consistent functional systems. We apply the method to data from a visual fMRI study comprised of 69 distinct stimulus images. The discovered system activation profiles correspond to selectivity for a number of image categories such as faces, bodies, and scenes. Among systems found by our method, we identify new areas that are deactivated by face stimuli. In empirical comparisons with previously proposed exploratory methods, our results appear superior in capturing the structure in the space of visual categories of stimuli.
Chen GH, Fedorenko EG, Kanwisher NG, Golland P. Deformation-Invariant Sparse Coding for Modeling Spatial Variability of Functional Patterns in the Brain. Mach Learn Interpret Neuroimaging (2011). 2012;7263 :68-75.Abstract
For a given cognitive task such as language processing, the location of corresponding functional regions in the brain may vary across subjects relative to anatomy. We present a probabilistic generative model that accounts for such variability as observed in fMRI data. We relate our approach to sparse coding that estimates a basis consisting of functional regions in the brain. Individual fMRI data is represented as a weighted sum of these functional regions that undergo deformations. We demonstrate the proposed method on a language fMRI study. Our method identified activation regions that agree with known literature on language processing and established correspondences among activation regions across subjects, producing more robust group-level effects than anatomical alignment alone.
O'Donnell LJ, Rigolo L, Norton I, Wells WM, Westin C-F, Golby AJ. fMRI-DTI modeling via landmark distance atlases for prediction and detection of fiber tracts. Neuroimage. 2012;60 (1) :456-70.Abstract
The overall goal of this research is the design of statistical atlas models that can be created from normal subjects, but may generalize to be applicable to abnormal brains. We present a new style of joint modeling of fMRI, DTI, and structural MRI. Motivated by the fact that a white matter tract and related cortical areas are likely to displace together in the presence of a mass lesion (brain tumor), in this work we propose a rotation and translation invariant model that represents the spatial relationship between fiber tracts and anatomic and functional landmarks. This landmark distance model provides a new basis for representation of fiber tracts and can be used for detection and prediction of fiber tracts based on landmarks. Our results indicate that the measured model is consistent across normal subjects, and thus suitable for atlas building. Our experiments demonstrate that the model is robust to displacement and missing data, and can be successfully applied to a small group of patients with mass lesions.
Tristán-Vega A, Aja-Fernández S, Westin C-F. Least squares for diffusion tensor estimation revisited: propagation of uncertainty with Rician and non-Rician signals. Neuroimage. 2012;59 (4) :4032-43.Abstract
Least Squares (LS) and its minimum variance counterpart, Weighted Least Squares (WLS), have become very popular when estimating the Diffusion Tensor (DT), to the point that they are the standard in most of the existing software for diffusion MRI. They are based on the linearization of the Stejskal-Tanner equation by means of the logarithmic compression of the diffusion signal. Due to the Rician nature of noise in traditional systems, a certain bias in the estimation is known to exist. This artifact has been made patent through some experimental set-ups, but it is not clear how the distortion translates in the reconstructed DT, and how important it is when compared to the other source of error contributing to the Mean Squared Error (MSE) in the estimate, i.e. the variance. In this paper we propose the analytical characterization of log-Rician noise and its propagation to the components of the DT through power series expansions. We conclude that even in highly noisy scenarios the bias for log-Rician signals remains moderate when compared to the corresponding variance. Yet, with the advent of Parallel Imaging (pMRI), the Rician model is not always valid. We make our analysis extensive to a number of modern acquisition techniques through the study of a more general Non Central-Chi (nc-χ) model. Since WLS techniques were initially designed bearing in mind Rician noise, it is not clear whether or not they still apply to pMRI. An important finding in our work is that the common implementation of WLS is nearly optimal when nc-χ noise is considered. Unfortunately, the bias in the estimation becomes far more important in this case, to the point that it may nearly overwhelm the variance in given situations. Furthermore, we evidence that such bias cannot be removed by increasing the number of acquired gradient directions. A number of experiments have been conducted that corroborate our analytical findings, while in vivo data have been used to test the actual relevance of the bias in the estimation.
Gao Y, Corn B, Schifter D, Tannenbaum A. Multiscale 3D shape representation and segmentation with applications to hippocampal/caudate extraction from brain MRI. Med Image Anal. 2012;16 (2) :374-85.Abstract
Extracting structure of interest from medical images is an important yet tedious work. Due to the image quality, the shape knowledge is widely used for assisting and constraining the segmentation process. In many previous works, shape knowledge was incorporated by first constructing a shape space from training cases, and then constraining the segmentation process to be within the learned shape space. However, such an approach has certain limitations due to the number of variations, eigen-shapemodes, that can be captured in the learned shape space. Moreover, small scale shape variances are usually overwhelmed by those in the large scale, and therefore the local shape information is lost. In this work, we present a multiscale representation for shapes with arbitrary topology, and a fully automatic method to segment the target organ/tissue from medical images using such multiscale shape information and local image features. First, we handle the problem of lacking eigen-shapemodes by providing a multiscale shape representation using the wavelet transform. Consequently, the shape variances existing in the training shapes captured by the statistical learning step are also represented at various scales. Note that by doing so, one can greatly enrich the eigen-shapemodes as well as capture small scale shape changes. Furthermore, in order to make full use of the training information, not only the shape but also the grayscale training images are utilized in a multi-atlas initialization procedure. By combining such initialization with the multiscale shape knowledge, we perform segmentation tests for challenging medical data sets where the target objects have low contrast and sharp corner structures, and demonstrate the statistically significant improvement obtained by employing such multiscale representation, in representing shapes as well as the overall shape based segmentation tasks.
Rosenberger G, Nestor PG, Oh JS, Levitt JJ, Kindleman G, Bouix S, Fitzsimmons J, Niznikiewicz M, Westin C-F, Kikinis R, et al. Anterior limb of the internal capsule in schizophrenia: a diffusion tensor tractography study. Brain Imaging Behav. 2012;6 (3) :417-25.Abstract
Thalamo-cortical feedback loops play a key role in the processing and coordination of processing and integration of perceptual inputs and outputs, and disruption in this connection has long been hypothesized to contribute significantly to neuropsychological disturbances in schizophrenia. To test this hypothesis, we applied diffusion tensor tractography to 18 patients suffering schizophrenia and 20 control subjects. Fractional anisotropy (FA) was evaluated in the bilateral anterior and posterior limbs of the internal capsule, and correlated with clinical and neurocognitive measures. Patients diagnosed with schizophrenia showed significantly reduced FA bilaterally in the anterior but not the posterior limb of the internal capsule, compared with healthy control subjects. Lower FA correlated with lower scores on tests of declarative episodic memory in the patient group only. These findings suggest that disruptions, bilaterally, in thalamo-cortical connections in schizophrenia may contribute to disease-related impairment in the coordination of mnemonic processes of encoding and retrieval that are vital for efficient learning of new information.
Mamata H, Tokuda J, Gill RR, Padera RF, Lenkinski RE, Sugarbaker DJ, Butler JP, Hatabu H. Clinical application of pharmacokinetic analysis as a biomarker of solitary pulmonary nodules: dynamic contrast-enhanced MR imaging. Magn Reson Med. 2012;68 (5) :1614-22.Abstract
The purpose of this study is to evaluate perfusion indices and pharmacokinetic parameters in solitary pulmonary nodules (SPNs). Thirty patients of 34 enrolled with SPNs (15-30 mm) were evaluated in this study. T1 and T2-weighted structural images and 2D turbo FLASH perfusion images were acquired with shallow free breathing. B-spline nonrigid image registration and optimization by χ² test against pharmacokinetic model curve were performed on dynamic contrast-enhanced MRI. This allowed voxel-by-voxel calculation of k(ep) , the rate constant for tracer transport to and from plasma and the extravascular extracellular space. Mean transit time, time-to-peak, initial slope, and maximum enhancement (E(max) ) were calculated from time-intensity curves fitted to a gamma variate function. After blinded data analysis, correlation with tissue histology from surgical resection or biopsy samples was performed. Histologic evaluation revealed 25 malignant and five benign SPNs. All benign SPNs had k(ep) < 1.0 min⁻¹. Nineteen of 25 (76%) malignant SPNs showed k(ep) > 1.0 min⁻¹. Sensitivity to diagnose malignant SPNs at a cutoff of k(ep) = 1.0 min⁻¹ was 76%, specificity was 100%, positive predictive value was 100%, negative predictive value was 45%, and accuracy was 80%. Of all indices studied, k(ep) was the most significant in differentiating malignant from benign SPNs.

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