Publications

2005
Ozarslan E, Vemuri BC, Mareci TH. Generalized scalar measures for diffusion MRI using trace, variance, and entropy. Magn Reson Med. 2005;53 (4) :866-76.Abstract
This paper details the derivation of rotationally invariant scalar measures from higher-rank diffusion tensors (DTs) and functions defined on a unit sphere. This was accomplished with the use of an expression that generalizes the evaluation of the trace operator to tensors of arbitrary rank, and even to functions whose domains are the unit sphere. It is shown that the mean diffusivity is invariant to the selection of tensor rank for the model used. However, this rank invariance does not apply to the anisotropy measures. Therefore, a variance-based, general anisotropy measure is proposed. Also an information theoretical parametrization of anisotropy is introduced that is frequently more consistent with the meaning attributed to anisotropy. We accomplished this by associating anisotropy with the amount of orientational information present in the data, regardless of the imaging technique used. Using a simplified model of fibrous tissue, we simulated anisotropy values with varying orientational complexity and tensor models. Simulations suggested that a lower-rank tensor model may produce artificially low anisotropy values in voxels with complex structure. This was confirmed with a spin-echo experiment performed on an excised rat brain.
Ozarslan E, Shepherd TM, Vemuri BC, Blackband SJ, Mareci TH. Fast orientation mapping from HARDI. Med Image Comput Comput Assist Interv. 2005;8 (Pt 1) :156-63.Abstract
This paper introduces a new, accurate and fast method for fiber orientation mapping using high angular resolution diffusion imaging (HARDI) data. The approach utilizes the Fourier relationship between the water displacement probabilities and diffusion attenuated magnetic resonance (MR) signal expressed in spherical coordinates. The Laplace series coefficients of the water displacement probabilities are evaluated at a fixed distance away from the origin. The computations take under one minute for most three-dimensional datasets. We present orientation maps computed from excised rat optic chiasm, brain and spinal cord images. The developed method will improve the reliability of tractography schemes and make it possible to correctly identify the neural connections between functionally connected regions of the nervous system.
O'Donnell L, Westin C-F. White matter tract clustering and correspondence in populations. Med Image Comput Comput Assist Interv. 2005;8 (Pt 1) :140-7.Abstract
We present a novel method for finding white matter fiber correspondences and clusters across a population of brains. Our input is a collection of paths from tractography in every brain. Using spectral methods we embed each path as a vector in a high dimensional space. We create the embedding space so that it is common across all brains, consequently similar paths in all brains will map to points near each other in the space. By performing clustering in this space we are able to find matching fiber tract clusters in all brains. In addition, we automatically obtain correspondence of tractographic paths across brains: by selecting one or several paths of interest in one brain, the most similar paths in all brains are obtained as the nearest points in the high-dimensional space.
Hoge SW, Westin C-F. Identification of translational displacements between N-dimensional data sets using the high-order SVD and phase correlation. IEEE Trans Image Process. 2005;14 (7) :884-9.Abstract
This paper presents an extension of the phase correlation image alignment method to N-dimensional data sets. By the Fourier shift theorem, the motion model for translational shifts between N-dimensional images can be represented as a rank-one tensor. Through use of a high-order singular value decomposition, the phase correlation between two N-dimensional data sets can be decomposed to independently identify translational displacements along each dimension with subpixel resolution. Using three-dimensional MRI data sets, we demonstrate the effectiveness of this approach relative to other N-dimensional image registration methods.
Wiegand LC, Warfield SK, Levitt JJ, Hirayasu Y, Salisbury DF, Heckers S, Bouix S, Schwartz D, Spencer M, Dickey CC, et al. An in vivo MRI study of prefrontal cortical complexity in first-episode psychosis. Am J Psychiatry. 2005;162 (1) :65-70.Abstract
OBJECTIVE: The purpose of this study was to investigate abnormalities in the surface complexity of the prefrontal cortex and in the hemispheric asymmetry of cortical complexity in first-episode patients with schizophrenia. METHOD: An estimate of the surface complexity of the prefrontal cortex was derived from the number of voxels along the boundary between gray matter and CSF. Magnetic resonance imaging scans were acquired from patients with a first episode of schizophrenia (N=17), patients with a first episode of affective psychosis (N=17), and normal comparison subjects (N=17), age-matched within a narrow age range (18-29 years). This study group was the focus of a previous study that showed lower prefrontal cortical volume in patients with schizophrenia. RESULTS: Prefrontal cortical complexity was not significantly different among the groups. However, the schizophrenia patients differed significantly from the normal comparison subjects in asymmetry, with the schizophrenia patients showing less left-greater-than-right asymmetry in cortical complexity than the comparison subjects. CONCLUSIONS: An abnormal pattern of asymmetry in the prefrontal cortex of first-episode patients with schizophrenia provides evidence for a neurodevelopmental mechanism in the etiology of schizophrenia.
Bouix S, Siddiqi K, Tannenbaum A. Flux driven automatic centerline extraction. Med Image Anal. 2005;9 (3) :209-21.Abstract
We present a fast, robust and automatic method for computing centerline paths through tubular structures for application to virtual endoscopy. The key idea is to utilize a skeletonization algorithm which exploits properties of the average outward flux of the gradient vector field of a Euclidean distance function from the boundary of the structure. The algorithm is modified to yield a collection of 3D curves, each of which is locally centered. The approach requires no user interaction, is virtually parameter free and has low computational complexity. We validate the method quantitatively on a number of synthetic data sets with known centerlines and qualitatively on colon and vessel data segmented from CT and CRA images.
Bouix S, Pruessner JC, Louis Collins D, Siddiqi K. Hippocampal shape analysis using medial surfaces. Neuroimage. 2005;25 (4) :1077-89.Abstract
In magnetic resonance imaging (MRI) research, significant attention has been paid to the analysis of the hippocampus (HC) within the medial temporal lobe because of its importance in memory and learning, and its role in neurodegenerative diseases. Manual segmentation protocols have established a volume decline in the HC in conjunction with Alzheimer's disease, epilepsy, post-traumatic stress disorder, and depression. Furthermore, recent studies have investigated age-related changes of HC volume which show an interaction with gender; in early adulthood, volume reduction of the HC is found in men but not in women. In this paper, we investigated gender differences in normal subjects in young adulthood by employing a shape analysis of the HC using medial surfaces. For each subject, the most prominent medial manifold of the HC was extracted and flattened. The flattened sheets were then registered using both a rigid and a non-rigid alignment technique, and the medial surface radius was expressed as a height function over them. This allowed for an investigation of the association between subject variables and the local width of the HC. With regard to the effects of age and gender, it could be shown that the previously observed gender differences were mostly due to volume loss in males in the lateral areas of the HC head and tail. We suggest that the analysis of HC shape using medial surfaces might thus serve as a complimentary technique to investigate group differences to the established segmentation protocols for volume quantification in MRI.
Martin-Fernandez M, Bouix S, Ungar L, McCarley RW, Shenton ME. Two methods for validating brain tissue classifiers. Med Image Comput Comput Assist Interv. 2005;8 (Pt 1) :515-22.Abstract
In this paper, we present an evaluation of seven automatic brain tissue classifiers based on level of agreements. A number of agreement measures are explained, and we show how they can be used to compare different segmentation techniques. We use the Simultaneous Truth and Performance Level Estimation (STAPLE) of Warfield et al. but also introduce a novel evaluation technique based on the Williams' index. The methods are evaluated using these two techniques on a population of forty subjects, each having an SPGR scan and a co-registered T2 weighted scan. We provide an interpretation of the results and show how similar the output of the STAPLE analysis and Williams' index are. When no ground truth is required, we recommend the use of Williams' index as it is easy and fast to compute.
2004
Fischl B, van der Kouwe A, Destrieux C, Halgren E, Ségonne F, Salat DH, Busa E, Seidman LJ, Goldstein J, Kennedy D, et al. Automatically parcellating the human cerebral cortex. Cereb Cortex. 2004;14 (1) :11-22.Abstract
We present a technique for automatically assigning a neuroanatomical label to each location on a cortical surface model based on probabilistic information estimated from a manually labeled training set. This procedure incorporates both geometric information derived from the cortical model, and neuroanatomical convention, as found in the training set. The result is a complete labeling of cortical sulci and gyri. Examples are given from two different training sets generated using different neuroanatomical conventions, illustrating the flexibility of the algorithm. The technique is shown to be comparable in accuracy to manual labeling.
Alberola-López C, Martín-Fernández M, Ruiz-Alzola J. Comments on: A methodology for evaluation of boundary detection algorithms on medical images. IEEE Trans Med Imaging. 2004;23 (5) :658-60.Abstract
In this paper we analyze a result previously published about a comparison between two statistical tests used for evaluation of boundary detection algorithms on medical images. We conclude that the statement made by Chalana and Kim (1997) about the performance of the percentage test has a weak theoretical foundation, and according to our results, is not correct. In addition, we propose a one-sided hypothesis test for which the acceptance region can be determined in advance, as opposed to the two-sided confidence intervals proposed in the original paper, which change according to the estimated quantity.
Sundberg M, Borga M, Knutsson H, Johansson A, Strömberg T, Oberg PA. Fibre-optic array for curvature assessment: application in otitis diagnosis. Med Biol Eng Comput. 2004;42 (2) :245-52.Abstract
A contact-free sensor consisting of two parallel optical-fibre arrays was designed to assess surface shapes of diffusely scattering media. By sequentially illuminating objects using one fibre array and detecting the diffusely back-scattered photons by the other, a source-detector intensity matrix was formed, where the matrix element (i, j) was the intensity at detector j when light source i was excited. Experimental data from convex and concave polyacetal plastic surfaces were recorded. A mathematical model was used for simulating source-detector intensity matrices for the surfaces analysed in the experiments. Experimental results from the system were compared with the theoretically expected results provided by the mathematical model. The shape and relative amplitude showed similar behaviour in the experiments and simulations. A convex/concave discriminator index D, representing the detected intensity difference between two source-detector separations, was defined. The relative dynamic range of D, defined as the difference between the maximum and the minimum divided by the mean of the index, was 1.37 for convex surfaces and 0.68 for concave surfaces, at a measuring distance of 4.5 mm. The index D was positive for convex surfaces and negative for concave surfaces, which showed that the system could distinguish between convex and concave surfaces, an important result for the diagnosis of otitis media.
Shin LM, Shin PS, Heckers S, Krangel TS, Macklin ML, Orr SP, Lasko N, Segal E, Makris N, Richert K, et al. Hippocampal function in posttraumatic stress disorder. Hippocampus. 2004;14 (3) :292-300.Abstract
Recent studies have reported memory deficits and reduced hippocampal volumes in posttraumatic stress disorder (PTSD). The goal of the current research was to use functional neuroimaging and a validated explicit memory paradigm to examine hippocampal function in PTSD. We used positron emission tomography (PET) and a word-stem completion task to study regional cerebral blood flow (rCBF) in the hippocampus in 16 firefighters: 8 with PTSD (PTSD group) and 8 without PTSD (Control group). During PET scanning, participants viewed three-letter word stems on a computer screen and completed each stem with a word they had previously encoded either deeply (High Recall condition) or shallowly (Low Recall condition). Relative to the Control group, the PTSD group exhibited significantly smaller rCBF increases in the left hippocampus in the High vs Low Recall comparison. However, this finding reflected relatively elevated rCBF in the Low Recall condition in the PTSD group. Collapsing across High and Low Recall conditions, (1) the PTSD group had higher rCBF in bilateral hippocampus and left amygdala than the Control group, and (2) within the PTSD group, symptom severity was positively associated with rCBF in hippocampus and parahippocampal gyrus. The groups did not significantly differ with regard to accuracy scores on the word-stem completion task. The PTSD group had significantly smaller right (and a trend for smaller left) hippocampal volumes than the Control group. The results suggest an abnormal rCBF response in the hippocampus during explicit recollection of nonemotional material in firefighters with PTSD, and that this abnormal response appears to be driven by relatively elevated hippocampal rCBF in the comparison condition.
Herbert MR, Ziegler DA, Makris N, Filipek PA, Kemper TL, Normandin JJ, Sanders HA, Kennedy DN, Caviness VS. Localization of white matter volume increase in autism and developmental language disorder. Ann Neurol. 2004;55 (4) :530-40.Abstract
Increased brain volume in autism appears to be driven mainly by an unexplained white matter enlargement, and we have reported a similar phenomenon in developmental language disorder (DLD). Localization of this enlargement would strongly guide research into its cause, tissue basis, and functional implications. We utilized a white matter parcellation technique that divides cerebral white matter into an outer zone containing the radiate compartment and an inner zone containing sagittal and bridging system compartments. In both high-functioning autism and DLD, enlargement localized to the radiate white matter (all lobes in autism, all but parietal in DLD), whereas inner zone white matter compartments showed no volume differences from controls. Furthermore, in both autism and DLD, later or longer-myelinating regions showed greater volume increases over controls. Neither group showed cerebral cortex, corpus callosum, or internal capsule volume differences from control. Radiate white matter myelinates later than deep white matter; this pattern of enlargement thus is consistent with striking postnatal head circumference percentile increases reported in autism. These findings suggest an ongoing postnatal process in both autism and DLD that is probably intrinsic to white matter, that primarily affects intrahemispheric and corticocortical connections, and that places these two disorders on the same spectrum.
Makris N, Gasic GP, Seidman LJ, Goldstein JM, Gastfriend DR, Elman I, Albaugh MD, Hodge SM, Ziegler DA, Sheahan FS, et al. Decreased absolute amygdala volume in cocaine addicts. Neuron. 2004;44 (4) :729-40.Abstract
The amygdala is instrumental to a set of brain processes that lead to cocaine consumption, including those that mediate reward and drug craving. This study examined the volumes of the amygdala and hippocampus in cocaine-addicted subjects and matched healthy controls and determined that the amygdala but not the hippocampus was significantly reduced in volume. The right-left amygdala asymmetry in control subjects was absent in the cocaine addicts. Topological analysis of amygdala isosurfaces (population averages) revealed that the isosurface of the cocaine-dependent group undercut the anterior and superior surfaces of the control group, implicating a difference in the corticomedial and basolateral nuclei. In cocaine addicts, amygdala volume did not correlate with any measure of cocaine use. The amygdala symmetry coefficient did correlate with baseline but not cocaine-primed craving. These findings argue for a condition that predisposes the individual to cocaine dependence by affecting the amygdala, or a primary event early in the course of cocaine use.
De Fossé L, Hodge SM, Makris N, Kennedy DN, Caviness VS, McGrath L, Steele S, Ziegler DA, Herbert MR, Frazier JA, et al. Language-association cortex asymmetry in autism and specific language impairment. Ann Neurol. 2004;56 (6) :757-66.Abstract
Language deficits are among the core impairments of autism. We previously reported asymmetry reversal of frontal language cortex in boys with autism. Specific language impairment (SLI) and autism share similar language deficits and may share genetic links. This study evaluated asymmetry of frontal language cortex in a new, independent sample of right-handed boys, including a new sample of boys with autism and a group of boys with SLI. The boys with autism were divided into those with language impairment (ALI) and those with normal language ability (ALN). Subjects (right-handed, aged 6.2-13.4 years) included 22 boys with autism (16 ALI and 6 ALN), 9 boys with a history of or present SLI, and 11 normal controls. MRI brain scans were segmented into grey and white matter; then the cerebral cortex was parcellated into 48 gyral-based divisions per hemisphere. Group differences in volumetric asymmetry were predicted a priori in language-related regions in inferior lateral frontal (Broca's area) and posterior superior temporal cortex. Language impaired boys with autism and SLI both had significant reversal of asymmetry in frontal language-related cortex; larger on the right side in both groups of language impaired boys and larger on the left in both unimpaired language groups, strengthening a phenotypic link between ALI and SLI. Thus, we replicated the observation of reversed asymmetry in frontal language cortex reported previously in an independent autism sample, and observed similar reversal in boys with SLI, further strengthening a phenotypic link between SLI and a subgroup of autism. Linguistically unimpaired boys with autism had similar asymmetry compared with the control group, suggesting that Broca's area asymmetry reversal is related more to language impairment than specifically to autism diagnosis.
Fischl B, Salat DH, van der Kouwe AJW, Makris N, Ségonne F, Quinn BT, Dale AM. Sequence-independent segmentation of magnetic resonance images. Neuroimage. 2004;23 Suppl 1 :S69-84.Abstract
We present a set of techniques for embedding the physics of the imaging process that generates a class of magnetic resonance images (MRIs) into a segmentation or registration algorithm. This results in substantial invariance to acquisition parameters, as the effect of these parameters on the contrast properties of various brain structures is explicitly modeled in the segmentation. In addition, the integration of image acquisition with tissue classification allows the derivation of sequences that are optimal for segmentation purposes. Another benefit of these procedures is the generation of probabilistic models of the intrinsic tissue parameters that cause MR contrast (e.g., T1, proton density, T2*), allowing access to these physiologically relevant parameters that may change with disease or demographic, resulting in nonmorphometric alterations in MR images that are otherwise difficult to detect. Finally, we also present a high band width multiecho FLASH pulse sequence that results in high signal-to-noise ratio with minimal image distortion due to B0 effects. This sequence has the added benefit of allowing the explicit estimation of T2* and of reducing test-retest intensity variability.
May FS, Chen CQ, Gilbertson MW, Shenton ME, Pitman RK. Cavum septum pellucidum in monozygotic twins discordant for combat exposure: relationship to posttraumatic stress disorder. Biol Psychiatry. 2004;55 (6) :656-8.Abstract
BACKGROUND: Abnormally large cavum septum pellucidum has been reported in posttraumatic stress disorder; however, the origin of this association is uncertain. METHODS: We utilized magnetic resonance imaging to measure cavum septum pellucidum in pairs of identical twins discordant for combat exposure in Vietnam. RESULTS: Presence of abnormal cavum septum pellucidum was significantly correlated between exposed and unexposed twins, indicating that it is partially determined by heredity and/or shared environment. There was a greater proportion of cavum septum pellucidum in combat-exposed twins with posttraumatic stress disorder and their noncombat-exposed co-twins. CONCLUSIONS: The presence of abnormally large cavum septum pellucidum is a familial vulnerability factor for posttraumatic stress disorder.
Kubicki M, Maier SE, Westin C-F, Mamata H, Ersner-Hershfield H, Estepar R, Kikinis R, Jolesz FA, McCarley RW, Shenton ME. Comparison of single-shot echo-planar and line scan protocols for diffusion tensor imaging. Acad Radiol. 2004;11 (2) :224-32.Abstract
RATIONALE AND OBJECTIVES: Both single-shot diffusion-weighted echo-planar imaging (EPI) and line scan diffusion imaging (LSDI) can be used to obtain magnetic resonance diffusion tensor data and to calculate directionally invariant diffusion anisotropy indices, ie, indirect measures of the organization and coherence of white matter fibers in the brain. To date, there has been no comparison of EPI and LSDI. Because EPI is the most commonly used technique for acquiring diffusion tensor data, it is important to understand the limitations and advantages of LSDI relative to EPI. MATERIALS AND METHODS: Five healthy volunteers underwent EPI and LSDI diffusion on a 1.5 Tesla magnet (General Electric Medical Systems, Milwaukee, WI). Four-mm thick coronal sections, covering the entire brain, were obtained. In addition, one subject was tested with both sequences over four sessions. For each image voxel, eigenvectors and eigenvalues of the diffusion tensor were calculated, and fractional anisotropy (FA) was derived. Several regions of interest were delineated, and for each, mean FA and estimated mean standard deviation were calculated and compared. RESULTS: Results showed no significant differences between EPI and LSDI for mean FA for the five subjects. When intersession reproducibility for one subject was evaluated, there was a significant difference between EPI and LSDI in FA for the corpus callosum and the right uncinate fasciculus. Moreover, errors associated with each FA measure were larger for EPI than for LSDI. CONCLUSION: Results indicate that both EPI- and LSDI-derived FA measures are sufficiently robust. However, when higher accuracy is needed, LSDI provides smaller error and smaller inter-subject and inter-session variability than EPI.
Schreyer AG, Fürst A, Agha A, Kikinis R, Scheibl K, Schölmerich J, Feuerbach S, Herfarth H, Seitz J. Magnetic resonance imaging based colonography for diagnosis and assessment of diverticulosis and diverticulitis. Int J Colorectal Dis. 2004;19 (5) :474-80.Abstract
BACKGROUND AND AIMS: MRI-based colonography is a new minimally invasive imaging modality to assess the colon and abdomen. This new method which is applied mainly for polyp screening could be an integrative approach for colonic diverticulitis assessment. This study evaluated the feasibility of MRI-based colonography to assess diverticulosis or diverticulitis. PATIENTS AND METHODS: Fourteen consecutive patients with clinically suspected diverticulitis were examined by MRI colonography on a 1.5-T scanner. All patients underwent abdominal CT as gold standard. N-Butyl-scopalamin was given intravenously to reduce bowel peristalsis. After rectal administration of a T1-positive enema T1- and T2-weighted acquisitions with additional intravenous contrast were obtained. A 3D FLASH sequence was acquired for virtual colonography. The results were compared with CT and biological parameters such as white blood cell count and C-reactive protein. RESULTS: Of 56 bowel segments (sigmoid colon, descending colon, transverse colon, ascending colon) in all 14 patients 54 were assessed to have good to fair image quality. Having CT as standard of reference, all sigmoid diverticula were diagnosed based on MRI. Inflammation as judged by CT was identically assessed on MRI. 3D models of the colon revealed further diverticula in the remaining colon; additionally, the 3D models gave a comprehensive image for surgical planning. CONCLUSION: In our preliminary study MRI colonography revealed the same diagnosis as CT in all patients without ionizing radiation. Additionally, 3D-rendered models and virtual colonoscopy can be performed. This comprehensive 3D models could replace presurgical planning barium enema with concurrent assessment of the residual colon.
Wiegand LC, Warfield SK, Levitt JJ, Hirayasu Y, Salisbury DF, Heckers S, Dickey CC, Kikinis R, Jolesz FA, McCarley RW, et al. Prefrontal cortical thickness in first-episode psychosis: a magnetic resonance imaging study. Biol Psychiatry. 2004;55 (2) :131-40.Abstract
BACKGROUND: Findings from postmortem studies suggest reduced prefrontal cortical thickness in schizophrenia; however, cortical thickness in first-episode schizophrenia has not been evaluated using magnetic resonance imaging (MRI). METHODS: Prefrontal cortical thickness was measured using MRI in first-episode schizophrenia patients (n = 17), first-episode affective psychosis patients (n = 17), and normal control subjects (n = 17); subjects were age-matched within 2 years and within a narrow age range (18-29 years). A previous study using the same subjects reported reduced prefrontal gray matter volume in first-episode schizophrenia. Manual editing was performed on those prefrontal segmentations before cortical thickness was measured. RESULTS: Prefrontal cortical thickness was not significantly different among groups. Prefrontal gray matter volume and thickness were, however, positively correlated in both schizophrenia and control subjects. The product of boundary complexity and thickness, an alternative measure of volume, was positively correlated with volume for all three groups. Finally, age and age at first medication were negatively correlated with prefrontal cortical thickness only in first-episode schizophrenia. CONCLUSIONS: This study demonstrates the potential usefulness of MRI for the study of cortical thickness abnormalities in schizophrenia. Correlations between cortical thickness and age and between cortical thickness and age at first medication suggest that the longer the schizophrenic process has been operative, the thinner the prefrontal cortex, although this needs confirmation in a longitudinal study.

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