Publications

2009
San José Estépar R, Westin C-F, Vosburgh KG. Towards real time 2D to 3D registration for ultrasound-guided endoscopic and laparoscopic procedures. Int J Comput Assist Radiol Surg. 2009;4 (6) :549-60.Abstract
PURPOSE: A method to register endoscopic and laparoscopic ultrasound (US) images in real time with pre-operative computed tomography (CT) data sets has been developed with the goal of improving diagnosis, biopsy guidance, and surgical interventions in the abdomen. METHODS: The technique, which has the potential to operate in real time, is based on a new phase correlation technique: LEPART, which specifies the location of a plane in the CT data which best corresponds to the US image. Validation of the method was carried out using an US phantom with cyst regions and with retrospective analysis of data sets from animal model experiments. RESULTS: The phantom validation study shows that local translation displacements can be recovered for each US frame with a root mean squared error of 1.56 +/- 0.78 mm in less than 5 sec, using non-optimized algorithm implementations. CONCLUSION: A new method for multimodality (preoperative CT and intraoperative US endoscopic images) registration to guide endoscopic interventions was developed and found to be efficient using clinically realistic datasets. The algorithm is inherently capable of being implemented in a parallel computing system so that full real time operation appears likely.
Kubicki M, Niznikiewicz M, Connor E, Ungar L, Nestor P, Bouix S, Dreusicke M, Kikinis R, McCarley R, Shenton M. Relationship Between White Matter Integrity, Attention, and Memory in Schizophrenia: A Diffusion Tensor Imaging Study. Brain Imaging Behav. 2009;3 (2) :191-201.Abstract
Attention and memory deficits are among the most prominent cognitive disturbances observed in schizophrenia. It has been suggested that a disruption in anatomical connectivity between areas involved in attentional control might be responsible for these abnormalities. We used Diffusion Tensor Tractography and Color Stroop/Negative Priming(NP) paradigm to investigate integrity of Cingulum Bundle(CB), the main white matter tract interconnecting these regions, and its relationship with executive functions in patients with schizophrenia and matched controls. The Fractional Anisotropy(FA), was calculated along the CB pathways, and correlated with reaction times for each Stroop item, and both Stroop, and NP effects. Patients with schizophrenia demonstrated decreased CB integrity and diminished NP effect, compared with controls, but both groups showed Stroop effect. For patients only, reaction times for every item, as well as for Stroop effect, correlated with left CB FA. These findings suggest that CB integrity disruptions might compromise the executive processes in schizophrenia.
Sabuncu MR, Yeo TBT, Van Leemput K, Fischl B, Golland P. Nonparametric Mixture Models for Supervised Image Parcellation. Med Image Comput Comput Assist Interv. 2009;12 (WS) :301-313.Abstract
We present a nonparametric, probabilistic mixture model for the supervised parcellation of images. The proposed model yields segmentation algorithms conceptually similar to the recently developed label fusion methods, which register a new image with each training image separately. Segmentation is achieved via the fusion of transferred manual labels. We show that in our framework various settings of a model parameter yield algorithms that use image intensity information differently in determining the weight of a training subject during fusion. One particular setting computes a single, global weight per training subject, whereas another setting uses locally varying weights when fusing the training data. The proposed nonparametric parcellation approach capitalizes on recently developed fast and robust pairwise image alignment tools. The use of multiple registrations allows the algorithm to be robust to occasional registration failures. We report experiments on 39 volumetric brain MRI scans with expert manual labels for the white matter, cerebral cortex, ventricles and subcortical structures. The results demonstrate that the proposed nonparametric segmentation framework yields significantly better segmentation than state-of-the-art algorithms.
Tristán-Vega A, Aja-Fernández S, Westin C-F. On the Blurring of the Funk–Radon Transform in Q–Ball Imaging. Med Image Comput Comput Assist Interv. 2009;12 (Pt 2) :415-22.Abstract

One known issue in Q-Ball imaging is the blurring in the radial integral defining the Orientation Distribution Function of fiber bundles, due to the computation of the Funk-Radon Transform (FRT). Three novel techniques to overcome this problem are presented, all of them based upon different assumptions about the behavior of the attenuation signal outside the sphere densely sampled from HARDI data sets. A systematic study with synthetic data has been carried out to show that the FRT blurring is not as important as the error introduced by some unrealistic assumptions, and only one of the three techniques (the one with the less restrictive assumption) improves the accuracy of Q-Balls.

Malcolm JG, Shenton ME, Rathi Y. Neural Tractography using an Unscented Kalman Filter. Inf Process Med Imaging. 2009;21 :126-38.Abstract

We describe a technique to simultaneously estimate a local neural fiber model and trace out its path. Existing techniques estimate the local fiber orientation at each voxel independently so there is no running knowledge of confidence in the estimated fiber model. We formulate fiber tracking as recursive estimation: at each step of tracing the fiber, the current estimate is guided by the previous. To do this we model the signal as a mixture of Gaussian tensors and perform tractography within a filter framework. Starting from a seed point, each fiber is traced to its termination using an unscented Kalman filter to simultaneously fit the local model 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. Synthetic experiments demonstrate that this approach reduces signal reconstruction error and significantly improves the angular resolution at crossings and branchings. In vivo experiments confirm the ability to trace out fibers in areas known to contain such crossing and branching while providing inherent path regularization.

Voineskos AN, O'Donnell LJ, Lobaugh NJ, Markant D, Ameis SH, Niethammer M, Mulsant BH, Pollock BG, Kennedy JL, Westin C-F, et al. Quantitative Examination of a Novel Clustering Method using Magnetic Resonance Diffusion Tensor Tractography. Neuroimage. 2009;45 (2) :370-6.Abstract

MR diffusion tensor imaging (DTI) can measure and visualize organization of white matter fibre tracts in vivo. DTI is a relatively new imaging technique, and new tools developed for quantifying fibre tracts require evaluation. The purpose of this study was to compare the reliability of a novel clustering approach with a multiple region of interest (MROI) approach in both healthy and disease (schizophrenia) populations. DTI images were acquired in 20 participants (n=10 patients with schizophrenia: 56+/-15 years; n=10 controls: 51+/-20 years) (1.5 T GE system) with diffusion gradients applied in 23 non-collinear directions, repeated three times. Whole brain seeding and creation of fibre tracts were then performed. Interrater reliability of the clustering approach, and the MROI approach, were each evaluated and the methods compared. There was high spatial (voxel-based) agreement within and between the clustering and MROI methods. Fractional anisotropy, trace, and radial and axial diffusivity values showed high intraclass correlation (p<0.001 for all tracts) for each approach. Differences in scalar indices of diffusion between the clustering and MROI approach were minimal. The excellent interrater reliability of the clustering method and high agreement with the MROI method, quantitatively and spatially, indicates that the clustering method can be used with confidence. The clustering method avoids biases of ROI drawing and placement, and, not limited by a priori predictions, may be a more robust and efficient way to identify and measure white matter tracts of interest.

O'Donnell LJ, Westin C-F, Golby AJ. Tract-Based Morphometry for White Matter Group Analysis.​​​​​​​. Neuroimage. 2009;45 (3) :832-44.Abstract

We introduce an automatic method that we call tract-based morphometry, or TBM, for measurement and analysis of diffusion MRI data along white matter fiber tracts. Using subject-specific tractography bundle segmentations, we generate an arc length parameterization of the bundle with point correspondences across all fibers and all subjects, allowing tract-based measurement and analysis. In this paper we present a quantitative comparison of fiber coordinate systems from the literature and we introduce an improved optimal match method that reduces spatial distortion and improves intra- and inter-subject variability of FA measurements. We propose a method for generating arc length correspondences across hemispheres, enabling a TBM study of interhemispheric diffusion asymmetries in the arcuate fasciculus (AF) and cingulum bundle (CB). The results of this study demonstrate that TBM can detect differences that may not be found by measuring means of scalar invariants in entire tracts, such as the mean diffusivity (MD) differences found in AF. We report TBM results of higher fractional anisotropy (FA) in the left hemisphere in AF (caused primarily by lower lambda(3), the smallest eigenvalue of the diffusion tensor, in the left AF), and higher left hemisphere FA in CB (related to higher lambda(1), the largest eigenvalue of the diffusion tensor, in the left CB). By mapping the significance levels onto the tractography trajectories for each structure, we demonstrate the anatomical locations of the interhemispheric differences. The TBM approach brings analysis of DTI data into the clinically and neuroanatomically relevant framework of the tract anatomy.

2008
Friedman L, Stern H, Brown GG, Mathalon DH, Turner J, Glover GH, Gollub RL, Lauriello J, Lim KO, Cannon T, et al. Test-retest and Between-site Reliability in a Multicenter fMRI Study. Hum Brain Mapp. 2008;29 (8) :958-72.Abstract

In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, www.nbirn.net). Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.

Wisco JJ, Killiany RJ, Guttmann CRG, Warfield SK, Moss MB, Rosene DL. An MRI study of age-related white and gray matter volume changes in the rhesus monkey. Neurobiol Aging. 2008;29 (10) :1563-75.Abstract
We applied the automated MRI segmentation technique Template Driven Segmentation (TDS) to dual-echo spin echo (DE SE) images of eight young (5-12 years), six middle-aged (16-19 years) and eight old (24-30 years) rhesus monkeys. We analyzed standardized mean volumes for 18 anatomically defined regions of interest (ROI's) and found an overall decrease from young to old age in the total forebrain (5.01%), forebrain parenchyma (5.24%), forebrain white matter (11.53%), forebrain gray matter (2.08%), caudate nucleus (11.79%) and globus pallidus (18.26%). Corresponding behavioral data for five of the young, five of the middle-aged and seven of the old subjects on the Delayed Non-matching to Sample (DNMS) task, the Delayed-recognition Span Task (DRST) and the Cognitive Impairment Index (CII) were also analyzed. We found that none of the cognitive measures were related to ROI volume changes in our sample size of monkeys.
Michailovich O, Tannenbaum A. On approximation of smooth functions from samples of partial derivatives with application to phase unwrapping. Signal Processing. 2008;88 (2) :358-374.Abstract
This paper addresses the problem of approximating smooth bivariate functions from the samples of their partial derivatives. The approximation is carried out under the assumption that the subspace to which the functions to be recovered are supposed to belong, possesses an approximant in the form of a principal shift-invariant (PSI) subspace. Subsequently, the desired approximation is found as the element of the PSI subspace that fits the data the best in the (2)-sense. In order to alleviate the ill-posedness of the process of finding such a solution, we take advantage of the discrete nature of the problem under consideration. The proposed approach allows the explicit construction of a projection operator which maps the measured derivatives into a stable and unique approximation of the corresponding function. Moreover, the paper develops the concept of discrete PSI subspaces, which may be of relevance for several practical settings where one is given samples of a function instead of its continuously defined values. As a final point, the application of the proposed method to the problem of phase unwrapping in homomorphic deconvolution is described.
Melonakos J, Pichon E, Angenent S, Tannenbaum A. Finsler active contours. IEEE Trans Pattern Anal Mach Intell. 2008;30 (3) :412-23.Abstract
In this paper, we propose an image segmentation technique based on augmenting the conformal (or geodesic) active contour framework with directional information. In the isotropic case, the Euclidean metric is locally multiplied by a scalar conformal factor based on image information such that the weighted length of curves lying on points of interest (typically edges) is small. The conformal factor which is chosen depends only upon position and is in this sense isotropic. While directional information has been studied previously for other segmentation frameworks, here we show that if one desires to add directionality in the conformal active contour framework, then one gets a well-defined minimization problem in the case that the factor defines a Finsler metric. Optimal curves may be obtained using the calculus of variations or dynamic programming based schemes. Finally we demonstrate the technique by extracting roads from aerial imagery, blood vessels from medical angiograms, and neural tracts from diffusion-weighted magnetic resonance imagery.
Malcolm J, Rathi Y, Tannenbaum A. A Graph Cut Approach to Image Segmentation in Tensor Space. Proc IEEE Comput Soc Conf Comput Vis Pattern Recognit. 2008 :1-8.Abstract
This paper proposes a novel method to apply the standard graph cut technique to segmenting multimodal tensor valued images. The Riemannian nature of the tensor space is explicitly taken into account by first mapping the data to a Euclidean space where non-parametric kernel density estimates of the regional distributions may be calculated from user initialized regions. These distributions are then used as regional priors in calculating graph edge weights. Hence this approach utilizes the true variation of the tensor data by respecting its Riemannian structure in calculating distances when forming probability distributions. Further, the non-parametric model generalizes to arbitrary tensor distribution unlike the Gaussian assumption made in previous works. Casting the segmentation problem in a graph cut framework yields a segmentation robust with respect to initialization on the data tested.
Karasev P, Malcolm J, Tannenbaum A. KERNEL-BASED HIGH-DIMENSIONAL HISTOGRAM ESTIMATION FOR VISUAL TRACKING. Proc Int Conf Image Proc. 2008 :2728-2731.Abstract
We propose an approach for non-rigid tracking that represents objects by their set of distribution parameters. Compared to joint histogram representations, a set of parameters such as mixed moments provides a significantly reduced size representation. The discriminating power is comparable to that of the corresponding full high-dimensional histogram yet at far less spatial and computational complexity. The proposed method is robust in the presence of noise and illumination changes, and provides a natural extension to the use of mixture models. Experiments demonstrate that the proposed method outperforms both full color mean-shift and global covariance searches.
Lankton S, Melonakos J, Malcolm J, Dambreville S, Tannenbaum A. Localized Statistics for DW-MRI Fiber Bundle Segmentation. Proc IEEE Comput Soc Conf Comput Vis Pattern Recognit. 2008 :1-8.Abstract
We describe a method for segmenting neural fiber bundles in diffusion-weighted magnetic resonance images (DWMRI). As these bundles traverse the brain to connect regions, their local orientation of diffusion changes drastically, hence a constant global model is inaccurate. We propose a method to compute localized statistics on orientation information and use it to drive a variational active contour segmentation that accurately models the non-homogeneous orientation information present along the bundle. Initialized from a single fiber path, the proposed method proceeds to capture the entire bundle. We demonstrate results using the technique to segment the cingulum bundle and describe several extensions making the technique applicable to a wide range of tissues.
Pujol S, Kikinis R, Gollub R. Lowering the barriers inherent in translating advances in neuroimage analysis to clinical research applications. Acad Radiol. 2008;15 (1) :114-8.Abstract
RATIONALE AND OBJECTIVES: This article presents an initiative for the translation of advances in neuroimage analysis techniques to clinical research scientists. Our objective is to bridge the gap between scientific advances made by the biomedical imaging community and their widespread use in the clinical research community. Through national collaborative effort supported by the National Institutes of Health Roadmap, the integration of the most sophisticated algorithms into usable working open-source systems enables clinical researchers to have access to a broad spectrum of cutting edge analysis techniques. A critical step to maximize the long-term positive impact of this collaborative effort is to translate these techniques into new skills of clinical researchers. To address this challenge, we developed a methodology based on three criteria: a multidisciplinary approach, a balance between theory and common practice, and an immersive collaborative environment. The article illustrates our initiative through the exemplar case of diffusion tensor imaging tractography, and reports on our experience over the past two years of designing and delivering training workshops to more than 300 clinicians and scientists using the developed methodology.
Talos I-F, Rubin DL, Halle M, Musen M, Kikinis R. A prototype symbolic model of canonical functional neuroanatomy of the motor system. J Biomed Inform. 2008;41 (2) :251-63.Abstract
Recent advances in bioinformatics have opened entire new avenues for organizing, integrating and retrieving neuroscientific data, in a digital, machine-processable format, which can be at the same time understood by humans, using ontological, symbolic data representations. Declarative information stored in ontological format can be perused and maintained by domain experts, interpreted by machines, and serve as basis for a multitude of decision support, computerized simulation, data mining, and teaching applications. We have developed a prototype symbolic model of canonical neuroanatomy of the motor system. Our symbolic model is intended to support symbolic look up, logical inference and mathematical modeling by integrating descriptive, qualitative and quantitative functional neuroanatomical knowledge. Furthermore, we show how our approach can be extended to modeling impaired brain connectivity in disease states, such as common movement disorders. In developing our ontology, we adopted a disciplined modeling approach, relying on a set of declared principles, a high-level schema, Aristotelian definitions, and a frame-based authoring system. These features, along with the use of the Unified Medical Language System (UMLS) vocabulary, enable the alignment of our functional ontology with an existing comprehensive ontology of human anatomy, and thus allow for combining the structural and functional views of neuroanatomy for clinical decision support and neuroanatomy teaching applications. Although the scope of our current prototype ontology is limited to a particular functional system in the brain, it may be possible to adapt this approach for modeling other brain functional systems as well.
Lankton S, Malcolm J, Nakhmani A, Tannenbaum A. Tracking through Changes in Scale. Proc Int Conf Image Proc. 2008 :241-4.Abstract
We propose a tracking system that is especially well-suited to tracking targets which change drastically in size or appearance. To accomplish this, we employ a fast, two phase template matching algorithm along with a periodic template update method. The template matching step ensures accurate localization while the template update scheme allows the target model to change over time along with the appearance of the target. Furthermore, the algorithm can deliver real-time results even when targets are very large. We demonstrate the proposed method with good results on several sequences showing targets which exhibit large changes in size, shape, and appearance.
Maddah M, Grimson EWL, Warfield SK, Wells WM. A unified framework for clustering and quantitative analysis of white matter fiber tracts. Med Image Anal. 2008;12 (2) :191-202.Abstract
We present a novel approach for joint clustering and point-by-point mapping of white matter fiber pathways. Knowledge of the point correspondence along the fiber pathways is not only necessary for accurate clustering of the trajectories into fiber bundles, but also crucial for any tract-oriented quantitative analysis. We employ an expectation-maximization (EM) algorithm to cluster the trajectories in a gamma mixture model context. The result of clustering is the probabilistic assignment of the fiber trajectories to each cluster, an estimate of the cluster parameters, i.e. spatial mean and variance, and point correspondences. The fiber bundles are modeled by the mean trajectory and its spatial variation. Point-by-point correspondence of the trajectories within a bundle is obtained by constructing a distance map and a label map from each cluster center at every iteration of the EM algorithm. This offers a time-efficient alternative to pairwise curve matching of all trajectories with respect to each cluster center. The proposed method has the potential to benefit from an anatomical atlas of fiber tracts by incorporating it as prior information in the EM algorithm. The algorithm is also capable of handling outliers in a principled way. The presented results confirm the efficiency and effectiveness of the proposed framework for quantitative analysis of diffusion tensor MRI.
Jolley M, Stinstra J, Pieper S, MacLeod R, Brooks DH, Cecchin F, Triedman JK. A computer modeling tool for comparing novel ICD electrode orientations in children and adults. Heart Rhythm. 2008;5 (4) :565-72.Abstract
BACKGROUND: Use of implantable cardiac defibrillators (ICDs) in children and patients with congenital heart disease is complicated by body size and anatomy. A variety of creative implantation techniques has been used empirically in these groups on an ad hoc basis. OBJECTIVE: To rationalize ICD placement in special populations, we used subject-specific, image-based finite element models (FEMs) to compare electric fields and expected defibrillation thresholds (DFTs) using standard and novel electrode configurations. METHODS: FEMs were created by segmenting normal torso computed tomography scans of subjects ages 2, 10, and 29 years and 1 adult with congenital heart disease into tissue compartments, meshing, and assigning tissue conductivities. The FEMs were modified by interactive placement of ICD electrode models in clinically relevant electrode configurations, and metrics of relative defibrillation safety and efficacy were calculated. RESULTS: Predicted DFTs for standard transvenous configurations were comparable with published results. Although transvenous systems generally predicted lower DFTs, a variety of extracardiac orientations were also predicted to be comparably effective in children and adults. Significant trend effects on DFTs were associated with body size and electrode length. In many situations, small alterations in electrode placement and patient anatomy resulted in significant variation of predicted DFT. We also show patient-specific use of this technique for optimization of electrode placement. CONCLUSION: Image-based FEMs allow predictive modeling of defibrillation scenarios and predict large changes in DFTs with clinically relevant variations of electrode placement. Extracardiac ICDs are predicted to be effective in both children and adults. This approach may aid both ICD development and patient-specific optimization of electrode placement. Further development and validation are needed for clinical or industrial utilization.
Yeo BTT, Ou W, Golland P. On the construction of invertible filter banks on the 2-sphere. IEEE Trans Image Process. 2008;17 (3) :283-300.Abstract
The theories of signal sampling, filter banks, wavelets, and "overcomplete wavelets" are well established for the Euclidean spaces and are widely used in the processing and analysis of images. While recent advances have extended some filtering methods to spherical images, many key challenges remain. In this paper, we develop theoretical conditions for the invertibility of filter banks under continuous spherical convolution. Furthermore, we present an analogue of the Papoulis generalized sampling theorem on the 2-Sphere. We use the theoretical results to establish a general framework for the design of invertible filter banks on the sphere and demonstrate the approach with examples of self-invertible spherical wavelets and steerable pyramids. We conclude by examining the use of a self-invertible spherical steerable pyramid in a denoising experiment and discussing the computational complexity of the filtering framework.

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