Publications by Year: 2009

Sampat MP, Berger AM, Healy BC, Hildenbrand P, Vass J, Meier DS, Chitnis T, Weiner HL, Bakshi R, Guttmann CRG. Regional white matter atrophy--based classification of multiple sclerosis in cross-sectional and longitudinal data. AJNR Am J Neuroradiol. 2009;30 (9) :1731-9.Abstract
BACKGROUND AND PURPOSE: The different clinical subtypes of multiple sclerosis (MS) may reflect underlying differences in affected neuroanatomic regions. Our aim was to analyze the effectiveness of jointly using the inferior subolivary medulla oblongata volume (MOV) and the cross-sectional area of the corpus callosum in distinguishing patients with relapsing-remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS), and primary-progressive multiple sclerosis (PPMS). MATERIALS AND METHODS: We analyzed a cross-sectional dataset of 64 patients (30 RRMS, 14 SPMS, 20 PPMS) and a separate longitudinal dataset of 25 patients (114 MR imaging examinations). Twelve patients in the longitudinal dataset had converted from RRMS to SPMS. For all images, the MOV and corpus callosum were delineated manually and the corpus callosum was parcellated into 5 segments. Patients from the cross-sectional dataset were classified as RRMS, SPMS, or PPMS by using a decision tree algorithm with the following input features: brain parenchymal fraction, age, disease duration, MOV, total corpus callosum area and areas of 5 segments of the corpus callosum. To test the robustness of the classification technique, we applied the results derived from the cross-sectional analysis to the longitudinal dataset. RESULTS: MOV and central corpus callosum segment area were the 2 features retained by the decision tree. Patients with MOV >0.94 cm(3) were classified as having RRMS. Patients with progressive MS were further subclassified as having SPMS if the central corpus callosum segment area was <55.12 mm(2), and as having PPMS otherwise. In the cross-sectional dataset, 51/64 (80%) patients were correctly classified. For the longitudinal dataset, 88/114 (77%) patient time points were correctly classified as RRMS or SPMS. CONCLUSIONS: Classification techniques revealed differences in affected neuroanatomic regions in subtypes of multiple sclerosis. The combination of central corpus callosum segment area and MOV provides good discrimination among patients with RRMS, SPMS, and PPMS.
Pohl KM, Sabuncu MR. A unified framework for MR based disease classification. Inf Process Med Imaging. 2009;21 :300-13.Abstract
In this paper, we employ an anatomical parameterization of spatial warps to reveal structural differences between medical images of healthy control subjects and disease patients. The warps are represented as structure-specific 9-parameter affine transformations, which constitute a global, non-rigid mapping between the atlas and image coordinates. Our method estimates the structure-specific transformation parameters directly from medical scans by minimizing a Kullback-Leibler divergence measure. The resulting parameters are then input to a linear Support Vector Machine classifier, which assigns individual scans to a specific clinical group. The classifier also enables us to interpret the anatomical differences between groups, as we can visualize the discriminative warp that best differentiates the two groups. We test the accuracy of our approach on a data set consisting of Magnetic Resonance scans from 16 first episode schizophrenics and 17 age-matched healthy control subjects. The data set also contains manual labels for four regions of interest in both hemispheres: superior temporal gyrus, amygdala, hippocampus, and para-hippocampal gyrus. On this small size data set, our approach, which performs classification based on the MR images directly, yields a leave-one-out cross-validation accuracy of up to 90%. This compares favorably with the accuracy achieved by state-of-the-art techniques in schizophrenia MRI research.
Tao R, Fletcher TP, Gerber S, Whitaker RT. A variational image-based approach to the correction of susceptibility artifacts in the alignment of diffusion weighted and structural MRI. Inf Process Med Imaging. 2009;21 :664-75.Abstract
This paper presents a method for correcting the geometric and greyscale distortions in diffusion-weighted MRI that result from inhomogeneities in the static magnetic field. These inhomogeneities may due to imperfections in the magnet or to spatial variations in the magnetic susceptibility of the object being imaged--so called susceptibility artifacts. Echo-planar imaging (EPI), used in virtually all diffusion weighted acquisition protocols, assumes a homogeneous static field, which generally does not hold for head MRI. The resulting distortions are significant, sometimes more than ten millimeters. These artifacts impede accurate alignment of diffusion images with structural MRI, and are generally considered an obstacle to the joint analysis of connectivity and structure in head MRI. In principle, susceptibility artifacts can be corrected by acquiring (and applying) a field map. However, as shown in the literature and demonstrated in this paper, field map corrections of susceptibility artifacts are not entirely accurate and reliable, and thus field maps do not produce reliable alignment of EPIs with corresponding structural images. This paper presents a new, image-based method for correcting susceptibility artifacts. The method relies on a variational formulation of the match between an EPI baseline image and a corresponding T2-weighted structural image but also specifically accounts for the physics of susceptibility artifacts. We derive a set of partial differential equations associated with the optimization, describe the numerical methods for solving these equations, and present results that demonstrate the effectiveness of the proposed method compared with field-map correction.
Gholami B, Haddad WM, Tannenbaum AR. Agitation and pain assessment using digital imaging. Conf Proc IEEE Eng Med Biol Soc. 2009;2009 :2176-9.Abstract
Pain assessment in patients who are unable to verbally communicate with medical staff is a challenging problem in patient critical care. The fundamental limitations in sedation and pain assessment in the intensive care unit (ICU) stem from subjective assessment criteria, rather than quantifiable, measurable data for ICU sedation and analgesia. This often results in poor quality and inconsistent treatment of patient agitation and pain from nurse to nurse. Recent advancements in pattern recognition techniques using a relevance vector machine algorithm can assist medical staff in assessing sedation and pain by constantly monitoring the patient and providing the clinician with quantifiable data for ICU sedation. In this paper, we show that the pain intensity assessment given by a computer classifier has a strong correlation with the pain intensity assessed by expert and non-expert human examiners.
Banks DC, Beason KM. Decoupling illumination from isosurface generation using 4D light transport. IEEE Trans Vis Comput Graph. 2009;15 (6) :1595-602.Abstract
One way to provide global illumination for the scientist who performs an interactive sweep through a 3D scalar dataset is to pre-compute global illumination, resample the radiance onto a 3D grid, then use it as a 3D texture. The basic approach of repeatedly extracting isosurfaces, illuminating them, and then building a 3D illumination grid suffers from the non-uniform sampling that arises from coupling the sampling of radiance with the sampling of isosurfaces. We demonstrate how the illumination step can be decoupled from the isosurface extraction step by illuminating the entire 3D scalar function as a 3-manifold in 4-dimensional space. By reformulating light transport in a higher dimension, one can sample a 3D volume without requiring the radiance samples to aggregate along individual isosurfaces in the pre-computed illumination grid.
Oguro S, Tokuda J, Elhawary H, Haker S, Kikinis R, Tempany CM, Hata N. MRI Signal Intensity Based B-Spline Nonrigid Registration for Pre- and Intraoperative Imaging during Prostate Brachytherapy. J Magn Reson Imaging. 2009;30 (5) :1052-8.Abstract

PURPOSE: To apply an intensity-based nonrigid registration algorithm to MRI-guided prostate brachytherapy clinical data and to assess its accuracy. MATERIALS AND METHODS: A nonrigid registration of preoperative MRI to intraoperative MRI images was carried out in 16 cases using a Basis-Spline algorithm in a retrospective manner. The registration was assessed qualitatively by experts' visual inspection and quantitatively by measuring the Dice similarity coefficient (DSC) for total gland (TG), central gland (CG), and peripheral zone (PZ), the mutual information (MI) metric, and the fiducial registration error (FRE) between corresponding anatomical landmarks for both the nonrigid and a rigid registration method. RESULTS: All 16 cases were successfully registered in less than 5 min. After the nonrigid registration, DSC values for TG, CG, PZ were 0.91, 0.89, 0.79, respectively, the MI metric was -0.19 +/- 0.07 and FRE presented a value of 2.3 +/- 1.8 mm. All the metrics were significantly better than in the case of rigid registration, as determined by one-sided t-tests. CONCLUSION: The intensity-based nonrigid registration method using clinical data was demonstrated to be feasible and showed statistically improved metrics when compare to only rigid registration. The method is a valuable tool to integrate pre- and intraoperative images for brachytherapy.

Ou W, Nummenmaa A, Golland P, Hamalainen MS. Multimodal functional imaging using fMRI-informed regional EEG/MEG source estimation. Conf Proc IEEE Eng Med Biol Soc. 2009;2009 :1926-9.Abstract
We propose a novel method, fMRI-Informed Regional Estimation (FIRE), which utilizes information from fMRI in E/MEG source reconstruction. FIRE takes advantage of the spatial alignment between the neural and the vascular activities, while allowing for substantial differences in their dynamics. Furthermore, with the regional approach, FIRE can be efficiently applied to a dense grid of sources. Inspection of our optimization procedure reveals that FIRE is related to the re-weighted minimum-norm algorithms, the difference being that the weights in the proposed approach are computed from both the current estimates and fMRI data. Analysis of both simulated and human fMRI-MEG data shows that FIRE reduces the ambiguities in source localization present in the minimum-norm estimates. Comparisons with several joint fMRI-E/MEG algorithms demonstrate robustness of FIRE in the presence of sources silent to either fMRI or E/MEG measurements.
Kindlmann GL, San José Estépar R, Smith SM, Westin C-F. Sampling and visualizing creases with scale-space particles. IEEE Trans Vis Comput Graph. 2009;15 (6) :1415-24.Abstract
Particle systems have gained importance as a methodology for sampling implicit surfaces and segmented objects to improve mesh generation and shape analysis. We propose that particle systems have a significantly more general role in sampling structure from unsegmented data. We describe a particle system that computes samplings of crease features (i.e. ridges and valleys, as lines or surfaces) that effectively represent many anatomical structures in scanned medical data. Because structure naturally exists at a range of sizes relative to the image resolution, computer vision has developed the theory of scale-space, which considers an n-D image as an (n+1)-D stack of images at different blurring levels. Our scale-space particles move through continuous four-dimensional scale-space according to spatial constraints imposed by the crease features, a particle-image energy that draws particles towards scales of maximal feature strength, and an inter-particle energy that controls sampling density in space and scale. To make scale-space practical for large three-dimensional data, we present a spline-based interpolation across scale from a small number of pre-computed blurrings at optimally selected scales. The configuration of the particle system is visualized with tensor glyphs that display information about the local Hessian of the image, and the scale of the particle. We use scale-space particles to sample the complex three-dimensional branching structure of airways in lung CT, and the major white matter structures in brain DTI.
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.