Publications

2005
Nierenberg J, Salisbury DF, Levitt JJ, David EA, McCarley RW, Shenton ME. Reduced left angular gyrus volume in first-episode schizophrenia. Am J Psychiatry. 2005;162 (8) :1539-41.Abstract
OBJECTIVE: Research suggests that the normal left-greater-than-right angular gyrus volume asymmetry is reversed in chronic schizophrenia. The authors examined whether angular gyrus volume and asymmetry were abnormal in patients with first-episode schizophrenia. METHOD: Magnetic resonance imaging scans were obtained from 14 inpatients at their first hospitalization for psychosis and 14 normal comparison subjects. Manual editing was undertaken to delineate postcentral, supramarginal, and angular gyri gray matter volumes. RESULTS: Group comparisons revealed that the left angular gyrus gray matter volume in patients was 14.8% less than that of the normal subjects. None of the other regions measured showed significant group volume or asymmetry differences. CONCLUSIONS: Patients with new-onset schizophrenia showed smaller left angular gyrus volumes than normal subjects, consistent with other studies showing parietal lobe volume abnormalities in schizophrenia. Angular gyrus pathology in first-episode patients suggests that the angular gyrus may be a neuroanatomical substrate for the expression of schizophrenia.
Zou KH, Greve DN, Wang M, Pieper SD, Warfield SK, White NS, Manandhar S, Brown GG, Vangel MG, Kikinis R, et al. Reproducibility of functional MR imaging: preliminary results of prospective multi-institutional study performed by Biomedical Informatics Research Network. Radiology. 2005;237 (3) :781-9.Abstract
PURPOSE: To prospectively investigate the factors--including subject, brain hemisphere, study site, field strength, imaging unit vendor, imaging run, and examination visit--affecting the reproducibility of functional magnetic resonance (MR) imaging activations based on a repeated sensory-motor (SM) task. MATERIALS AND METHODS: The institutional review boards of all participating sites approved this HIPAA-compliant study. All subjects gave informed consent. Functional MR imaging data were repeatedly acquired from five healthy men aged 20-29 years who performed the same SM task at 10 sites. Five 1.5-T MR imaging units, four 3.0-T units, and one 4.0-T unit were used. The subjects performed bilateral finger tapping on button boxes with a 3-Hz audio cue and a reversing checkerboard. In a block design, 15-second epochs of alternating baseline and tasks yielded 85 acquisitions per run. Functional MR images were acquired with block-design echo-planar or spiral gradient-echo sequences. Brain activation maps standardized in a unit-sphere for the left and right hemispheres of each subject were constructed. Areas under the receiver operating characteristic curve, intraclass correlation coefficients, multiple regression analysis, and paired Student t tests were used for statistical analyses. RESULTS: Significant factors were subject (P < .005), k-space (P < .005), and field strength (P = .02) for sensitivity and subject (P = .03) and k-space (P = .05) for specificity. At 1.5-T MR imaging, mean sensitivities ranged from 7% to 32% and mean specificities were higher than 99%. At 3.0 T, mean sensitivities and specificities ranged from 42% to 85% and from 96% to 99%, respectively. At 4.0 T, mean sensitivities and specificities ranged from 41% to 73% and from 95% to 99%, respectively. Mean areas under the receiver operating characteristic curve (+/- their standard errors) were 0.77 +/- 0.05 at 1.5 T, 0.90 +/- 0.09 at 3.0 T, and 0.95 +/- 0.02 at 4.0 T, with significant differences between the 1.5- and 3.0-T examinations and between the 1.5- and 4.0-T examinations (P < .01 for both comparisons). Intraclass correlation coefficients ranged from 0.49 to 0.71. CONCLUSION: MR imaging at 3.0- and 4.0-T yielded higher reproducibility across sites and significantly better results than 1.5-T imaging. The effects of subject, k-space, and field strength on examination reproducibility were significant.
Clatz O, Delingette H, Talos I-F, Golby AJ, Kikinis R, Jolesz FA, Ayache N, Warfield SK. Robust nonrigid registration to capture brain shift from intraoperative MRI. IEEE Trans Med Imaging. 2005;24 (11) :1417-27.Abstract
We present a new algorithm to register 3-D preoperative magnetic resonance (MR) images to intraoperative MR images of the brain which have undergone brain shift. This algorithm relies on a robust estimation of the deformation from a sparse noisy set of measured displacements. We propose a new framework to compute the displacement field in an iterative process, allowing the solution to gradually move from an approximation formulation (minimizing the sum of a regularization term and a data error term) to an interpolation formulation (least square minimization of the data error term). An outlier rejection step is introduced in this gradual registration process using a weighted least trimmed squares approach, aiming at improving the robustness of the algorithm. We use a patient-specific model discretized with the finite element method in order to ensure a realistic mechanical behavior of the brain tissue. To meet the clinical time constraint, we parallelized the slowest step of the algorithm so that we can perform a full 3-D image registration in 35 s (including the image update time) on a heterogeneous cluster of 15 personal computers. The algorithm has been tested on six cases of brain tumor resection, presenting a brain shift of up to 14 mm. The results show a good ability to recover large displacements, and a limited decrease of accuracy near the tumor resection cavity.
Savadjiev P, Campbell JSW, Pike BG, Siddiqi K. 3D curve inference for diffusion MRI regularization. Med Image Comput Comput Assist Interv. 2005;8 (Pt 1) :123-30.Abstract
We develop a differential geometric framework for regularizing diffusion MRI data. The key idea is to model white matter fibers as 3D space curves and to then extend Parent and Zucker's 2D curve inference approach [8] by using a notion of co-helicity to indicate compatibility between fibre orientation estimates at each voxel with those in a local neighborhood. We argue that this provides several advantages over earlier regularization methods. We validate the approach quantitatively on a biological phantom and on synthetic data, and qualitatively on data acquired in vivo from a human brain.
Wittek A, Kikinis R, Warfield SK, Miller K. Brain shift computation using a fully nonlinear biomechanical model. Med Image Comput Comput Assist Interv. 2005;8 (Pt 2) :583-90.Abstract
In the present study, fully nonlinear (i.e. accounting for both geometric and material nonlinearities) patient specific finite element brain model was applied to predict deformation field within the brain during the craniotomy-induced brain shift. Deformation of brain surface was used as displacement boundary conditions. Application of the computed deformation field to align (i.e. register) the preoperative images with the intraoperative ones indicated that the model very accurately predicts the displacements of gravity centers of the lateral ventricles and tumor even for very limited information about the brain surface deformation. These results are sufficient to suggest that nonlinear biomechanical models can be regarded as one possible way of complementing medical image processing techniques when conducting nonrigid registration. Important advantage of such models over the linear ones is that they do not require unrealistic assumptions that brain deformations are infinitesimally small and brain tissue stress-strain relationship is linear.
Kubicki M, McCarley RW, Shenton ME. Evidence for white matter abnormalities in schizophrenia. Curr Opin Psychiatry. 2005;18 (2) :121-34.Abstract
PURPOSE OF REVIEW: The purpose of this review is to highlight important recent imaging, histological, and genetic findings relevant to white matter abnormalities in schizophrenia. It is cast within the context of research findings conducted over the last 5 years, where we analyze their importance in understanding schizophrenia, as well as discuss future directions for research. RECENT FINDINGS: White matter abnormalities have long been hypothesized in schizophrenia, although only recently has it become possible to investigate them more closely. This has come about as a result of advances in neuroimaging, including new imaging techniques sensitive to white matter structure, as well as advances in computer science, with new analysis techniques making it possible to evaluate several interconnected brain regions at a time. Postmortem studies, with advances such as fluoroscopy and electron microscopy, have also led to quantifying populations of different brain cells, including myelin-forming oligodendrocytes. Moreover, molecular studies enable examination of immunoreactivity of proteins that are responsible for building myelin sheaths. Additionally, microarray genetic studies allow us to investigate myelin-related genes in schizophrenia. Taken together, these technological advances bring us closer to understanding white matter pathology in schizophrenia. SUMMARY: Advances in new imaging techniques likely account for the renewed interest in investigating white matter abnormalities in schizophrenia, with over 30 new articles published on this topic in the last 12 months, compared with 11 the year before. We review recent imaging, histological, and genetic findings that suggest white matter abnormalities in schizophrenia.
Clatz O, Delingette H, Talos I-F, Golby AJ, Kikinis R, Jolesz FA, Ayache N, Warfield SK. Hybrid formulation of the model-based non-rigid registration problem to improve accuracy and robustness. Med Image Comput Comput Assist Interv. 2005;8 (Pt 2) :295-302.Abstract
We present a new algorithm to register 3D pre-operative Magnetic Resonance (MR) images with intra-operative MR images of the brain. This algorithm relies on a robust estimation of the deformation from a sparse set of measured displacements. We propose a new framework to compute iteratively the displacement field starting from an approximation formulation (minimizing the sum of a regularization term and a data error term) and converging toward an interpolation formulation (least square minimization of the data error term). The robustness of the algorithm is achieved through the introduction of an outliers rejection step in this gradual registration process. We ensure the validity of the deformation by the use of a biomechanical model of the brain specific to the patient, discretized with the finite element method. The algorithm has been tested on six cases of brain tumor resection, presenting a brain shift up to 13 mm.
Pohl KM, Fisher J, Levitt JJ, Shenton ME, Kikinis R, Grimson EWL, Wells WM. A unifying approach to registration, segmentation, and intensity correction. Med Image Comput Comput Assist Interv. 2005;8 (Pt 1) :310-8.Abstract
We present a statistical framework that combines the registration of an atlas with the segmentation of magnetic resonance images. We use an Expectation Maximization-based algorithm to find a solution within the model, which simultaneously estimates image inhomogeneities, anatomical labelmap, and a mapping from the atlas to the image space. An example of the approach is given for a brain structure-dependent affine mapping approach. The algorithm produces high quality segmentations for brain tissues as well as their substructures. We demonstrate the approach on a set of 22 magnetic resonance images. In addition, we show that the approach performs better than similar methods which separate the registration and segmentation problems.
Yoo S-S, Park H-J, Soul JS, Mamata H, Park HW, Westin C-F, Bassan H, Du Plessis AJ, Robertson RL, Maier SE, et al. In vivo visualization of white matter fiber tracts of preterm- and term-infant brains with diffusion tensor magnetic resonance imaging. Invest Radiol. 2005;40 (2) :110-5.Abstract
OBJECTIVE: The goal of this study was to test the feasibility of visualizing a 3-dimensional structure of cerebral white matter fiber tracts in preterm infants, postconceptional age (PCA) 28 weeks to term, by using volumetric diffusion tensor magnetic resonance imaging (DTI) data. MATERIALS AND METHOD: We combined tractography algorithms and visualization methods, currently available for adult DTI data, to trace the pixelated principal direction of a diffusion tensor originating from regions-of-interest with high fractional anisotropy. Consequently, white matter fiber bundles from the genu and the splenium of corpus callosum, the corticospinal tracts, the inferior fronto-occipital fasciculi, and optic radiations were visualized. RESULTS: Our results suggest that major white matter tracts of preterm infant brains, with PCAs ranging from 28 weeks to term (40 weeks old), can be successfully visualized despite the small brain volume and low anisotropy. CONCLUSION: The feasibility of fiber tractography in preterm neonates with DTI may add a new dimension in detection and characterization of white matter injuries of preterm infants.
Kubicki M, Westin C-F, McCarley RW, Shenton ME. The application of DTI to investigate white matter abnormalities in schizophrenia. Ann N Y Acad Sci. 2005;1064 :134-48.Abstract
Schizophrenia is a serious and disabling mental disorder that affects approximately 1% of the general population, with often devastating effects on the psychological and financial resources of the patient, family, and larger community. The etiology of schizophrenia is not known, although it likely involves several interacting biological and environmental factors that predispose an individual to schizophrenia. However, although the underlying pathology remains unknown, it has been believed that brain abnormalities would ultimately be linked to the etiology of schizophrenia. This theory was rekindled in the 1970s, when the first computer-assisted tomography (CT) study showed enlarged lateral ventricles in schizophrenia. Since that time, there have been many improvements in MR acquisition and image processing, including the introduction of positron emission tomography (PET), followed by functional MR (fMRI), and diffusion tensor imaging (DTI). These advances have led to an appreciation of the critical role that brain abnormalities play in schizophrenia. While structural MRI has proven to be useful in investigating and detecting gray matter abnormalities in schizophrenia, the investigation of white matter has proven to be more challenging as white matter appears homogeneous on conventional MRI and the fibers connecting different brain regions cannot be appreciated. With the development of DTI, we are now able to investigate white matter abnormalities in schizophrenia.
Warfield SK, Haker SJ, Talos I-F, Kemper CA, Weisenfeld N, Mewes AUJ, Goldberg-Zimring D, Zou KH, Westin C-F, Wells WM, et al. Capturing intraoperative deformations: research experience at Brigham and Women's Hospital. Med Image Anal. 2005;9 (2) :145-62.Abstract
During neurosurgical procedures the objective of the neurosurgeon is to achieve the resection of as much diseased tissue as possible while achieving the preservation of healthy brain tissue. The restricted capacity of the conventional operating room to enable the surgeon to visualize critical healthy brain structures and tumor margin has lead, over the past decade, to the development of sophisticated intraoperative imaging techniques to enhance visualization. However, both rigid motion due to patient placement and nonrigid deformations occurring as a consequence of the surgical intervention disrupt the correspondence between preoperative data used to plan surgery and the intraoperative configuration of the patient's brain. Similar challenges are faced in other interventional therapies, such as in cryoablation of the liver, or biopsy of the prostate. We have developed algorithms to model the motion of key anatomical structures and system implementations that enable us to estimate the deformation of the critical anatomy from sequences of volumetric images and to prepare updated fused visualizations of preoperative and intraoperative images at a rate compatible with surgical decision making. This paper reviews the experience at Brigham and Women's Hospital through the process of developing and applying novel algorithms for capturing intraoperative deformations in support of image guided therapy.
Nakamura M, McCarley RW, Kubicki M, Dickey CC, Niznikiewicz MA, Voglmaier MM, Seidman LJ, Maier SE, Westin C-F, Kikinis R, et al. Fronto-temporal disconnectivity in schizotypal personality disorder: a diffusion tensor imaging study. Biol Psychiatry. 2005;58 (6) :468-78.Abstract
BACKGROUND: Using diffusion tensor imaging (DTI), we previously reported abnormalities in two critical white matter tracts in schizophrenia, the uncinate fasciculus (UF) and the cingulum bundle (CB), both related to fronto-temporal connectivity. Here, we investigate these two bundles in unmedicated subjects with schizotypal personality disorder (SPD). METHODS: Fifteen male SPD subjects and 15 male control subjects were scanned with line-scan DTI. Fractional anisotropy (FA) and mean diffusivity (D(m)) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Exploratory correlation analyses were evaluated with Spearman's rho, followed by post hoc hierarchical regression analyses. RESULTS: We found bilaterally reduced FA in the UF of SPD subjects. For CB, there was no significant group difference for FA or D(m) measures. Additionally, in SPD, reduced FA in the right UF was correlated with clinical symptoms, including ideas of reference, suspiciousness, restricted affect, and social anxiety. In contrast, left UF area was correlated with measures of cognitive function, including general intelligence, verbal and visual memory, and executive performance. CONCLUSIONS: These findings in SPD suggest altered fronto-temporal connectivity through the UF, similar to findings in schizophrenia, and intact neocortical-limbic connectivity through the CB, in marked contrast with what has been reported in schizophrenia.
Simmross-Wattenberg F, Carranza-Herrezuelo N, Palacios-Camarero C, Casaseca-de-la-Higuera P, Martín-Fernández MA, Aja-Fernández S, Ruiz-Alzola J, Westin C-F, Alberola-López C. Group-Slicer: a collaborative extension of 3D-Slicer. J Biomed Inform. 2005;38 (6) :431-42.Abstract
In this paper, we describe a first step towards a collaborative extension of the well-known 3D-Slicer; this platform is nowadays used as a standalone tool for both surgical planning and medical intervention. We show how this tool can be easily modified to make it collaborative so that it may constitute an integrated environment for expertise exchange as well as a useful tool for academic purposes.
Friman O, Westin C-F. Resampling fMRI time series. Neuroimage. 2005;25 (3) :859-67.Abstract
The problem of selecting a threshold for the statistical parameter maps in functional MRI (fMRI) is a delicate issue. The use of advanced test statistics and/or the complex dependence structure of fMRI noise may preclude parametric statistical methods for finding appropriate thresholds. Non-parametric statistical methodology has been presented as a feasible alternative. In this paper, we discuss resampling methods for finding thresholds in single subject fMRI analysis. It is shown that the presence of a BOLD response in the time series biases the estimation of the temporal autocorrelation, which in turn leads to biased thresholds. Therefore, proposed resampling methods based on Fourier and wavelet transforms, which employ implicit and weak models of the temporal noise characteristic, may produce erroneous thresholds. In contrast, resampling based on a pre-whitening transform, which is driven by an explicit noise model, is robust to the presence of a BOLD response. The size of the bias is, however, largely dependent on the complexity of the experimental design. While blocked designs can induce large biases, event-related designs generate significantly smaller biases. Results supporting these claims are provided.
Verhey JF, Wisser J, Keller T, Westin C-F, Kikinis R. Rigid overlay of volume sonography and MR image data of the female pelvic floor using a fiducial based alignment--feasibility due to a case series. Comput Med Imaging Graph. 2005;29 (4) :243-9.Abstract
The visual combination of different medical image acquisition techniques (modalities) can lead to new modalities with enhanced informative content. In this paper, we present an overlay technique of magnetic resonance (MR) and 3D US image data sets of the female anal canal (internal and external sphincter) as a base for a new diagnostic modality. It is a new field of the application of the overlay technique. Three corresponding MR and US volume data sets from the female pelvic floor region were filtered using adaptive filtering techniques and overlayed (=registered rigidly) with a landmark based alignment method.
Luboz V, Wu X, Krissian K, Westin C-F, Kikinis R, Cotin S, Dawson S. A segmentation and reconstruction technique for 3D vascular structures. Med Image Comput Comput Assist Interv. 2005;8 (Pt 1) :43-50.Abstract
In the context of stroke therapy simulation, a method for the segmentation and reconstruction of human vasculature is presented and evaluated. Based on CTA scans, semi-automatic tools have been developed to reduce dataset noise, to segment using active contours, to extract the skeleton, to estimate the vessel radii and to reconstruct the associated surface. The robustness and accuracy of our technique are evaluated on a vascular phantom scanned in different orientations. The reconstructed surface is compared to a surface generated by marching cubes followed by decimation and smoothing. Experiments show that the proposed technique reaches a good balance in terms of smoothness, number of triangles, and distance error. The reconstructed surface is suitable for real-time simulation, interactive navigation and visualization.
Friman O, Westin C-F. Uncertainty in white matter fiber tractography. Med Image Comput Comput Assist Interv. 2005;8 (Pt 1) :107-14.Abstract
In this work we address the uncertainty associated with fiber paths obtained in white matter fiber tractography. This uncertainty, which arises for example from noise and partial volume effects, is quantified using a Bayesian modeling framework. The theory for estimating the probability of a connection between two areas in the brain is presented, and a new model of the local water diffusion profile is introduced. We also provide a theorem that facilitates the estimation of the parameters in this diffusion model, making the presented method simple to implement.
Pichon E, Westin C-F, Tannenbaum AR. A Hamilton-Jacobi-Bellman approach to high angular resolution diffusion tractography. Med Image Comput Comput Assist Interv. 2005;8 (Pt 1) :180-7.Abstract
This paper describes a new framework for white matter tractography in high angular resolution diffusion data. A direction-dependent local cost is defined based on the diffusion data for every direction on the unit sphere. Minimum cost curves are determined by solving the Hamilton-Jacobi-Bellman using an efficient algorithm. Classical costs based on the diffusion tensor field can be seen as a special case. While the minimum cost (or equivalently the travel time of a particle moving along the curve) and the anisotropic front propagation frameworks are related, front speed is related to particle speed through a Legendre transformation which can severely impact anisotropy information for front propagation techniques. Implementation details and results on high angular diffusion data show that this method can successfully take advantage of the increased angular resolution in high b-value diffusion weighted data despite lower signal to noise ratio.
Mendonça PRS, Padfield DR, Ross JC, Miller JV, Dutta S, Gautham SM. Quantification of emphysema severity by histogram analysis of CT scans. Med Image Comput Comput Assist Interv. 2005;8 (Pt 1) :738-44.Abstract
Emphysema is characterized by the destruction and over distension of lung tissue, which manifest on high resolution computer tomography (CT) images as regions of low attenuation. Typically, it is diagnosed by clinical symptoms, physical examination, pulmonary function tests, and X-ray and CT imaging. In this paper we discuss a quantitative imaging approach to analyze emphysema which employs low-level segmentations of CT images that partition the data into perceptually relevant regions. We constructed multi-dimensional histograms of feature values computed over the image segmentation. For each region in the segmentation, we derive a rich set of feature measurements. While we can use any combination of physical and geometric features, we found that limiting the scope to two features - the mean attenuation across a region and the region area - is effective. The subject histogram is compared to a set of canonical histograms representative of various stages of emphysema using the Earth Mover's Distance metric. Disease severity is assigned based on which canonical histogram is most similar to the subject histogram. Experimental results with 81 cases of emphysema at different stages of disease progression show good agreement against the reading of an expert radiologist.
Ross JC, Langan D, Manjeshwar R, Kaufhold J, Manak J, Wilson D. Registration and integration for fluoroscopy device enhancement. Med Image Comput Comput Assist Interv. 2005;8 (Pt 1) :851-8.Abstract
We investigated a method, motion compensated integration (MCI), for enhancing stent Contrast-to-Noise Ratio (CNR) such that stent deployment may be more easily assessed. MCI registers fluoroscopic frames on the basis of stent motion and performs pixel-wise integration to reduce noise. Registration is based on marker balls, high contrast interventional devices which guide the clinician in stent placement. It is assumed that stent motion is identical to that of the marker balls. Detecting marker balls and identifying their centroids with a high degree of accuracy is a non-trivial task. To address the required registration accuracy, in this work we examine MCI's visualization benefit as a function of registration error. We employ adaptive forced choice experiments to quantify human discrimination fidelity. Perception results are contrasted with CNR measurements. For each level of registration inaccuracy investigated, MCI conferred a benefit (p < 0.05) on stent deployment assessment suggesting the technique is tolerant of modest registration error. We also consider the blurring effect of cardiac motion during the x-ray pulse and select frames for integration as a function of cardiac phase imaged.

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