Publications by Year: 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, 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.
Kazanzides P, Xia T, Baird C, Jallo G, Hayes K, Nakajima N, Hata N. A cooperatively-controlled image guided robot system for skull base surgery. Stud Health Technol Inform. 2008;132 :198-203.Abstract
We created an image-guided robot system to assist with skull base drilling by integrating a robot, a commercial navigation system, and an open source visualization platform. The objective of this procedure is to create a cavity in the skull base to allow access for neurosurgical interventions. The motivation for introducing an image-guided robot is to improve safety by preventing the surgeon from accidentally damaging critical structures during the drilling procedure. Our approach is to attach the cutting tool to the robot end-effector and operate the robot in a cooperative control mode, where robot motion is determined from the forces and torques applied by the surgeon. We employ "virtual fixtures" to constrain the motion of the cutting tool so that it remains in the safe zone that was defined on a preoperative CT scan. This paper presents the system design and the results of phantom and cadaveric experiments. Both experiments have demonstrated the feasibility of the system, with average overcut error at about 1 mm and maximum errors at 2.5 mm.
Malcolm J, Rathi Y, Yezzi A, Tannenbaum A. Fast approximate surface evolution in arbitrary dimension. Proc SPIE Int Soc Opt Eng. 2008;6914.Abstract
The level set method is a popular technique used in medical image segmentation; however, the numerics involved make its use cumbersome. This paper proposes an approximate level set scheme that removes much of the computational burden while maintaining accuracy. Abandoning a floating point representation for the signed distance function, we use integral values to represent the signed distance function. For the cases of 2D and 3D, we detail rules governing the evolution and maintenance of these three regions. Arbitrary energies can be implemented in the framework. This scheme has several desirable properties: computations are only performed along the zero level set; the approximate distance function requires only a few simple integer comparisons for maintenance; smoothness regularization involves only a few integer calculations and may be handled apart from the energy itself; the zero level set is represented exactly removing the need for interpolation off the interface; and evolutions proceed on the order of milliseconds per iteration on conventional uniprocessor workstations. To highlight its accuracy, flexibility and speed, we demonstrate the technique on intensity-based segmentations under various statistical metrics. Results for 3D imagery show the technique is fast even for image volumes.
Lodygensky GA, Seghier ML, Warfield SK, Tolsa CB, Sizonenko S, Lazeyras F, Hüppi PS. Intrauterine growth restriction affects the preterm infant's hippocampus. Pediatr Res. 2008;63 (4) :438-43.Abstract
The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants' Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants' Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency.
Hershkovits E, Tannenbaum A, Tannenbaum R. Scaling aspects of block co-polymer adsorption on curved surfaces from nonselective solvents. J Phys Chem B. 2008;112 (17) :5317-26.Abstract
In this paper, we have developed a geometric-based scaling model that describes the adsorption of diblock copolymer chains from good solvents and theta-solvents onto reactive surfaces of varying curvatures. To evaluate the impact of particle size on the adsorption process, we probed the adsorption of poly(styrene-b-methymethacrylate) (PS-PMMA) diblock copolymers from solvents with different degrees of selectivity on aluminum oxide (Al(2)O(3)) surfaces belonging to particles of different sizes. When the adsorbed PMMA layer is dense enough (in the case of a theta-solvent for the PMMA block), our results show good correlation between the theory and experimental results, pointing to the formation of a PMMA adsorption layer and a brushlike PS layer. Conversely, when adsorption occurs from a nonpreferential solvent, particularly on particles with high curvature, the PMMA adsorption layer at the surface becomes less dense and the grafted PS moiety exhibits a transitional morphology consisting of several layers of increasingly sparsely spaced blobs.
Duan Y, Hildenbrand PG, Sampat MP, Tate DF, Csapo I, Moraal B, Bakshi R, Barkhof F, Meier DS, Guttmann CRG. Segmentation of subtraction images for the measurement of lesion change in multiple sclerosis. AJNR Am J Neuroradiol. 2008;29 (2) :340-6.Abstract
BACKGROUND AND PURPOSE: Lesion volume change (LVC) assessment is essential in monitoring MS progression. LVC is usually measured by independently segmenting serial MR imaging examinations. Subtraction imaging has been proposed for improved visualization and characterization of lesion change. We compare segmentation of subtraction images (SSEG) with serial single time-point conventional segmentation (CSEG) by assessing the LVC relationship to brain atrophy and disease duration, as well as scan-rescan reproducibility and annual rates of lesion accrual. MATERIALS AND METHODS: Pairs of scans were acquired 1.5 to 4.7 years apart in 21 patients with multiple sclerosis (MS). Scan-rescan MR images were acquired within 30 minutes in 10 patients with MS. LVC was measured with CSEG and SSEG after coregistration and normalization. Coefficient of variation (COV) and Bland-Altman analyses estimated method reproducibility. Spearman rank correlations probed associations between LVC and other measures. RESULTS: Atrophy rate and net LVC were associated for SSEG (R = -0.446; P < .05) but not when using CSEG (R = -0.180; P = .421). Disease duration did not show an association with net lesion volume change per year measured by CSEG (R = -0.360; P = .11) but showed an inverse correlation with SSEG-derived measurements (R = -0.508; P < .05). Scan-rescan COV was lower for SSEG (0.98% +/- 1.55%) than for CSEG (8.64% +/- 9.91%). CONCLUSION: SSEG unveiled a relationship between T2 LVC and concomitant brain atrophy and demonstrated significantly higher measurement reproducibility. SSEG, a promising tool providing detailed analysis of subtle alterations in lesion size and intensity, may provide critical outcome measures for clinical trials of novel treatments, and may provide further insight into progression patterns in MS.
Holland CM, Smith EE, Csapo I, Gurol ME, Brylka DA, Killiany RJ, Blacker D, Albert MS, Guttmann CRG, Greenberg SM. Spatial distribution of white-matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy aging. Stroke. 2008;39 (4) :1127-33.Abstract
BACKGROUND AND PURPOSE: White-matter hyperintensities (WMHs) detected by magnetic resonance imaging are thought to represent the effects of cerebral small-vessel disease and neurodegenerative changes. We sought to determine whether the spatial distribution of WMHs discriminates between different disease groups and healthy aging individuals and whether these distributions are related to local cerebral perfusion patterns. METHODS: We examined the pattern of WMHs by T2/fluid-attenuated inversion recovery-weighted magnetic resonance imaging in 3 groups of subjects: cerebral amyloid angiopathy (n=32), Alzheimer disease or mild cognitive impairment (n=41), and healthy aging (n=29). WMH frequency maps were calculated for each group, and spatial distributions were compared by voxel-wise logistic regression. WMHs were also analyzed as a function of normal cerebral perfusion patterns by overlaying a single photon emission computed tomography atlas. RESULTS: Although WMH volume was greater in cerebral amyloid angiopathy and Alzheimer disease/mild cognitive impairment than in healthy aging, there was no consistent difference in the spatial distributions when controlling for total WMH volume. Hyperintensities were most frequent in the deep periventricular WM in all 3 groups. A strong inverse correlation between hyperintensity frequency and normal perfusion was demonstrated in all groups, demonstrating that WMHs were most common in regions of relatively lower normal cerebral perfusion. CONCLUSIONS: WMHs show a common distribution pattern and predilection for cerebral WM regions with lower atlas-derived perfusion, regardless of the underlying diagnosis. These data suggest that across diverse disease processes, WM injury may occur in a pattern that reflects underlying tissue properties, such as relative perfusion.
Warfield SK, Zou KH, Wells III WM. Validation of Image Segmentation by Estimating Rater Bias and Variance. Philos Trans A Math Phys Eng Sci. 2008;366 (1874) :2361-75.Abstract

The accuracy and precision of segmentations of medical images has been difficult to quantify in the absence of a 'ground truth' or reference standard segmentation for clinical data. Although physical or digital phantoms can help by providing a reference standard, they do not allow the reproduction of the full range of imaging and anatomical characteristics observed in clinical data. An alternative assessment approach is to compare with segmentations generated by domain experts. Segmentations may be generated by raters who are trained experts or by automated image analysis algorithms. Typically, these segmentations differ due to intra-rater and inter-rater variability. The most appropriate way to compare such segmentations has been unclear. We present here a new algorithm to enable the estimation of performance characteristics, and a true labelling, from observations of segmentations of imaging data where segmentation labels may be ordered or continuous measures. This approach may be used with, among others, surface, distance transform or level-set representations of segmentations, and can be used to assess whether or not a rater consistently overestimates or underestimates the position of a boundary.