Publications by Year: 2012

2012
Chariker JH, Naaz F, Pani JR. Item difficulty in the evaluation of computer-based instruction: an example from neuroanatomy. Anat Sci Educ. 2012;5 (2) :63-75.Abstract
This article reports large item effects in a study of computer-based learning of neuroanatomy. Outcome measures of the efficiency of learning, transfer of learning, and generalization of knowledge diverged by a wide margin across test items, with certain sets of items emerging as particularly difficult to master. In addition, the outcomes of comparisons between instructional methods changed with the difficulty of the items to be learned. More challenging items better differentiated between instructional methods. This set of results is important for two reasons. First, it suggests that instruction may be more efficient if sets of consistently difficult items are the targets of instructional methods particularly suited to them. Second, there is wide variation in the published literature regarding the outcomes of empirical evaluations of computer-based instruction. As a consequence, many questions arise as to the factors that may affect such evaluations. The present article demonstrates that the level of challenge in the material that is presented to learners is an important factor to consider in the evaluation of a computer-based instructional system.
Casaseca-de-la-Higuera P, Tristán-Vega A, Aja-Fernández S, Alberola-López C, Westin C-F, San José Estépar R. Optimal real-time estimation in diffusion tensor imaging. Magn Reson Imaging. 2012;30 (4) :506-17.Abstract
Diffusion tensor imaging (DTI) constitutes the most used paradigm among the diffusion-weighted magnetic resonance imaging (DW-MRI) techniques due to its simplicity and application potential. Recently, real-time estimation in DW-MRI has deserved special attention, with several proposals aiming at the estimation of meaningful diffusion parameters during the repetition time of the acquisition sequence. Specifically focusing on DTI, the underlying model of the noise present in the acquired data is not taken into account, leading to a suboptimal estimation of the diffusion tensor. In this paper, we propose an optimal real-time estimation framework for DTI reconstruction in single-coil acquisitions. By including an online estimation of the time-changing noise variance associated to the acquisition process, the proposed method achieves the sequential best linear unbiased estimator. Results on both synthetic and real data show that our method outperforms those so far proposed, reaching the best performance of the existing proposals by processing a substantially lower number of diffusion images.
Nakhmani A, Tannenbaum A. Self-crossing Detection and Location for Parametric active Contours. IEEE Trans Image Process. 2012;21 (7) :3150-6.Abstract
Active contours are very popular tools for video tracking and image segmentation. Parameterized contours are used due to their fast evolution and have become the method of choice in the Sobolev context. Unfortunately, these contours are not easily adaptable to topological changes, and they may sometimes develop undesirable loops, resulting in erroneous results. To solve such topological problems, one needs an algorithm for contour self-crossing detection. We propose a simple methodology via simple techniques from differential topology. The detection is accomplished by inspecting the total net change of a given contour's angle, without point sorting and plane sweeping. We discuss the efficient implementation of the algorithm. We also provide algorithms for locating crossings by angle considerations and by plotting the four-connected lines between the discrete contour points. The proposed algorithms can be added to any parametric active-contour model. We show examples of successful tracking in real-world video sequences by Sobolev active contours and the proposed algorithms and provide ideas for further research.
Gao Y, Kikinis R, Bouix S, Shenton M, Tannenbaum A. A 3D interactive multi-object segmentation tool using local robust statistics driven active contours. Med Image Anal. 2012;16 (6) :1216-27.Abstract
Extracting anatomical and functional significant structures renders one of the important tasks for both the theoretical study of the medical image analysis, and the clinical and practical community. In the past, much work has been dedicated only to the algorithmic development. Nevertheless, for clinical end users, a well designed algorithm with an interactive software is necessary for an algorithm to be utilized in their daily work. Furthermore, the software would better be open sourced in order to be used and validated by not only the authors but also the entire community. Therefore, the contribution of the present work is twofolds: first, we propose a new robust statistics based conformal metric and the conformal area driven multiple active contour framework, to simultaneously extract multiple targets from MR and CT medical imagery in 3D. Second, an open source graphically interactive 3D segmentation tool based on the aforementioned contour evolution is implemented and is publicly available for end users on multiple platforms. In using this software for the segmentation task, the process is initiated by the user drawn strokes (seeds) in the target region in the image. Then, the local robust statistics are used to describe the object features, and such features are learned adaptively from the seeds under a non-parametric estimation scheme. Subsequently, several active contours evolve simultaneously with their interactions being motivated by the principles of action and reaction-this not only guarantees mutual exclusiveness among the contours, but also no longer relies upon the assumption that the multiple objects fill the entire image domain, which was tacitly or explicitly assumed in many previous works. In doing so, the contours interact and converge to equilibrium at the desired positions of the desired multiple objects. Furthermore, with the aim of not only validating the algorithm and the software, but also demonstrating how the tool is to be used, we provide the reader reproducible experiments that demonstrate the capability of the proposed segmentation tool on several public available data sets.
Fedorov A, Beichel R, Kalpathy-Cramer J, Finet J, Fillion-Robin J-C, Pujol S, Bauer C, Jennings D, Fennessy F, Sonka M, et al. 3D Slicer as an image computing platform for the Quantitative Imaging Network. Magn Reson Imaging. 2012;30 (9) :1323-41.Abstract
Quantitative analysis has tremendous but mostly unrealized potential in healthcare to support objective and accurate interpretation of the clinical imaging. In 2008, the National Cancer Institute began building the Quantitative Imaging Network (QIN) initiative with the goal of advancing quantitative imaging in the context of personalized therapy and evaluation of treatment response. Computerized analysis is an important component contributing to reproducibility and efficiency of the quantitative imaging techniques. The success of quantitative imaging is contingent on robust analysis methods and software tools to bring these methods from bench to bedside. 3D Slicer is a free open-source software application for medical image computing. As a clinical research tool, 3D Slicer is similar to a radiology workstation that supports versatile visualizations but also provides advanced functionality such as automated segmentation and registration for a variety of application domains. Unlike a typical radiology workstation, 3D Slicer is free and is not tied to specific hardware. As a programming platform, 3D Slicer facilitates translation and evaluation of the new quantitative methods by allowing the biomedical researcher to focus on the implementation of the algorithm and providing abstractions for the common tasks of data communication, visualization and user interface development. Compared to other tools that provide aspects of this functionality, 3D Slicer is fully open source and can be readily extended and redistributed. In addition, 3D Slicer is designed to facilitate the development of new functionality in the form of 3D Slicer extensions. In this paper, we present an overview of 3D Slicer as a platform for prototyping, development and evaluation of image analysis tools for clinical research applications. To illustrate the utility of the platform in the scope of QIN, we discuss several use cases of 3D Slicer by the existing QIN teams, and we elaborate on the future directions that can further facilitate development and validation of imaging biomarkers using 3D Slicer.
Gao Y, Rathi Y, Bouix S, Tannenbaum A. Filtering in the diffeomorphism group and the registration of point sets. IEEE Trans Image Process. 2012;21 (10) :4383-96.Abstract
The registration of a pair of point sets as well as the estimation of their pointwise correspondences is a challenging and important task in computer vision. In this paper, we present a method to estimate the diffeomorphic deformation, together with the pointwise correspondences, between a pair of point sets. Many of the registration problems are iteratively solved by estimating the correspondence, locally optimizing certain cost functionals over the rigid or similarity or affine transformation group, then estimating the correspondence again, and so on. This type of approach, however, is well-known to be susceptible to suboptimal local solutions. In this paper, we first adopt the perspective of treating the registration as a posterior estimation optimization problem and solve it accordingly via a particle-filtering framework. Second, within such a framework, the diffeomorphic registration is performed to correct the nonlinear deformation of the points. In doing so, we provide a solution less susceptible to local minima. We provide the experimental results, which include challenging medical data sets where the two point sets differ by 180 (°) rotation as well as local deformations, to highlight the algorithm's capability of robustly finding the more globally optimal solution for the registration task.
Kikinis Z, Asami T, Bouix S, Finn CT, Ballinger T, Tworog-Dube E, Kucherlapati R, Kikinis R, Shenton ME, Kubicki M. Reduced Fractional Anisotropy and Axial Diffusivity in White Matter in 22q11.2 Deletion Syndrome: A Pilot Study. Schizophr Res. 2012;141 (1) :35-9.Abstract
Individuals with 22q11.2 deletion syndrome (22q11.2DS) evince a 30% incidence of schizophrenia. We compared the white matter (WM) of 22q11.2DS patients without schizophrenia to a group of matched healthy controls using Tract-Based-Spatial-Statistics (TBSS). We found localized reduction of Fractional Anisotropy (FA) and Axial Diffusivity (AD; measure of axonal integrity) in WM underlying the left parietal lobe. No changes in Radial Diffusivity (RD; measure of myelin integrity) were observed. Of note, studies in chronic schizophrenia patients report reduced FA, no changes in AD, and increases in RD in WM. Our findings suggest different WM microstructural pathology in 22q11.2DS than in patients with schizophrenia.
Shenton ME, Hamoda HM, Schneiderman JS, Bouix S, Pasternak O, Rathi Y, Vu M-A, Purohit MP, Helmer KG, Koerte IK, et al. A Review of Magnetic Resonance Imaging and Diffusion Tensor Imaging Findings in Mild Traumatic Brain Injury. Brain Imaging Behav. 2012;6 (2) :137-92.Abstract

Mild traumatic brain injury (mTBI), also referred to as concussion, remains a controversial diagnosis because the brain often appears quite normal on conventional computed tomography (CT) and magnetic resonance imaging (MRI) scans. Such conventional tools, however, do not adequately depict brain injury in mTBI because they are not sensitive to detecting diffuse axonal injuries (DAI), also described as traumatic axonal injuries (TAI), the major brain injuries in mTBI. Furthermore, for the 15 to 30 % of those diagnosed with mTBI on the basis of cognitive and clinical symptoms, i.e., the "miserable minority," the cognitive and physical symptoms do not resolve following the first 3 months post-injury. Instead, they persist, and in some cases lead to long-term disability. The explanation given for these chronic symptoms, i.e., postconcussive syndrome, particularly in cases where there is no discernible radiological evidence for brain injury, has led some to posit a psychogenic origin. Such attributions are made all the easier since both posttraumatic stress disorder (PTSD) and depression are frequently co-morbid with mTBI. The challenge is thus to use neuroimaging tools that are sensitive to DAI/TAI, such as diffusion tensor imaging (DTI), in order to detect brain injuries in mTBI. Of note here, recent advances in neuroimaging techniques, such as DTI, make it possible to characterize better extant brain abnormalities in mTBI. These advances may lead to the development of biomarkers of injury, as well as to staging of reorganization and reversal of white matter changes following injury, and to the ability to track and to characterize changes in brain injury over time. Such tools will likely be used in future research to evaluate treatment efficacy, given their enhanced sensitivity to alterations in the brain. In this article we review the incidence of mTBI and the importance of characterizing this patient population using objective radiological measures. Evidence is presented for detecting brain abnormalities in mTBI based on studies that use advanced neuroimaging techniques. Taken together, these findings suggest that more sensitive neuroimaging tools improve the detection of brain abnormalities (i.e., diagnosis) in mTBI. These tools will likely also provide important information relevant to outcome (prognosis), as well as play an important role in longitudinal studies that are needed to understand the dynamic nature of brain injury in mTBI. Additionally, summary tables of MRI and DTI findings are included. We believe that the enhanced sensitivity of newer and more advanced neuroimaging techniques for identifying areas of brain damage in mTBI will be important for documenting the biological basis of postconcussive symptoms, which are likely associated with subtle brain alterations, alterations that have heretofore gone undetected due to the lack of sensitivity of earlier neuroimaging techniques. Nonetheless, it is noteworthy to point out that detecting brain abnormalities in mTBI does not mean that other disorders of a more psychogenic origin are not co-morbid with mTBI and equally important to treat. They arguably are. The controversy of psychogenic versus physiogenic, however, is not productive because the psychogenic view does not carefully consider the limitations of conventional neuroimaging techniques in detecting subtle brain injuries in mTBI, and the physiogenic view does not carefully consider the fact that PTSD and depression, and other co-morbid conditions, may be present in those suffering from mTBI. Finally, we end with a discussion of future directions in research that will lead to the improved care of patients diagnosed with mTBI.

Cooper RJ, Caffini M, Dubb J, Fang Q, Custo A, Tsuzuki D, Fischl B, Wells W, Dan I, Boas DA. Validating atlas-guided DOT: a comparison of diffuse optical tomography informed by atlas and subject-specific anatomies. Neuroimage. 2012;62 (3) :1999-2006.Abstract
We describe the validation of an anatomical brain atlas approach to the analysis of diffuse optical tomography (DOT). Using MRI data from 32 subjects, we compare the diffuse optical images of simulated cortical activation reconstructed using a registered atlas with those obtained using a subject's true anatomy. The error in localization of the simulated cortical activations when using a registered atlas is due to a combination of imperfect registration, anatomical differences between atlas and subject anatomies and the localization error associated with diffuse optical image reconstruction. When using a subject-specific MRI, any localization error is due to diffuse optical image reconstruction only. In this study we determine that using a registered anatomical brain atlas results in an average localization error of approximately 18 mm in Euclidean space. The corresponding error when the subject's own MRI is employed is 9.1 mm. In general, the cost of using atlas-guided DOT in place of subject-specific MRI-guided DOT is a doubling of the localization error. Our results show that despite this increase in error, reasonable anatomical localization is achievable even in cases where the subject-specific anatomy is unavailable.
Gao Y, Li Z, Lin Z, Zhu L, Tannenbaum A, Bouix S, Wong CP. Automated dispersion and orientation analysis for carbon nanotube reinforced polymer composites. Nanotechnology. 2012;23 (43) :435706.Abstract
The properties of carbon nanotube (CNT)/polymer composites are strongly dependent on the dispersion and orientation of CNTs in the host matrix. Quantification of the dispersion and orientation of CNTs by means of microstructure observation and image analysis has been demonstrated as a useful way to understand the structure-property relationship of CNT/polymer composites. However, due to the various morphologies and large amount of CNTs in one image, automatic and accurate identification of CNTs has become the bottleneck for dispersion/orientation analysis. To solve this problem, shape identification is performed for each pixel in the filler identification step, so that individual CNTs can be extracted from images automatically. The improved filler identification enables more accurate analysis of CNT dispersion and orientation. The dispersion index and orientation index obtained for both synthetic and real images from model compounds correspond well with the observations. Moreover, these indices help to explain the electrical properties of CNT/silicone composite, which is used as a model compound. This method can also be extended to other polymer composites with high-aspect-ratio fillers.
Pasternak O, Westin C-F, Bouix S, Seidman LJ, Goldstein JM, Woo T-UW, Petryshen TL, Mesholam-Gately RI, McCarley RW, Kikinis R, et al. Excessive extracellular volume reveals a neurodegenerative pattern in schizophrenia onset. J Neurosci. 2012;32 (48) :17365-72.Abstract
Diffusion MRI has been successful in identifying the existence of white matter abnormalities in schizophrenia in vivo. However, the role of these abnormalities in the etiology of schizophrenia is not well understood. Accumulating evidence from imaging, histological, genetic, and immunochemical studies support the involvement of axonal degeneration and neuroinflammation--ubiquitous components of neurodegenerative disorders--as the underlying pathologies of these abnormalities. Nevertheless, the current imaging modalities cannot distinguish neuroinflammation from axonal degeneration, and therefore provide little specificity with respect to the pathophysiology progression and whether it is related to a neurodegenerative process. Free-water imaging is a new methodology that is sensitive to water molecules diffusing in the extracellular space. Excessive extracellular volume is a surrogate biomarker for neuroinflammation and can be separated out to reveal abnormalities such as axonal degeneration that affect diffusion characteristics in the tissue. We applied free-water imaging on diffusion MRI data acquired from schizophrenia-diagnosed human subjects with a first psychotic episode. We found a significant increase in the extracellular volume in both white and gray matter. In contrast, significant signs of axonal degeneration were limited to focal areas in the frontal lobe white matter. Our findings demonstrate that neuroinflammation is more prominent than axonal degeneration in the early stage of schizophrenia, revealing a pattern shared by many neurodegenerative disorders, in which prolonged inflammation leads to axonal degeneration. These findings promote anti-inflammatory treatment for early diagnosed schizophrenia patients.
Venkataraman A, Kubicki M, Golland P. From brain connectivity models to identifying foci of a neurological disorder. Med Image Comput Comput Assist Interv. 2012;15 (Pt 1) :715-22.Abstract
We propose a novel approach to identify the foci of a neurological disorder based on anatomical and functional connectivity information. Specifically, we formulate a generative model that characterizes the network of abnormal functional connectivity emanating from the affected foci. We employ the variational EM algorithm to fit the model and to identify both the afflicted regions and the differences in connectivity induced by the disorder. We demonstrate our method on a population study of schizophrenia.
Egger J, Kapur T, Nimsky C, Kikinis R. Pituitary adenoma volumetry with 3D Slicer. PLoS One. 2012;7 (12) :e51788.Abstract
In this study, we present pituitary adenoma volumetry using the free and open source medical image computing platform for biomedical research: (3D) Slicer. Volumetric changes in cerebral pathologies like pituitary adenomas are a critical factor in treatment decisions by physicians and in general the volume is acquired manually. Therefore, manual slice-by-slice segmentations in magnetic resonance imaging (MRI) data, which have been obtained at regular intervals, are performed. In contrast to this manual time consuming slice-by-slice segmentation process Slicer is an alternative which can be significantly faster and less user intensive. In this contribution, we compare pure manual segmentations of ten pituitary adenomas with semi-automatic segmentations under Slicer. Thus, physicians drew the boundaries completely manually on a slice-by-slice basis and performed a Slicer-enhanced segmentation using the competitive region-growing based module of Slicer named GrowCut. Results showed that the time and user effort required for GrowCut-based segmentations were on average about thirty percent less than the pure manual segmentations. Furthermore, we calculated the Dice Similarity Coefficient (DSC) between the manual and the Slicer-based segmentations to proof that the two are comparable yielding an average DSC of 81.97±3.39%.
Zhu L, Gao Y, Yezzi A, MacLeod R, Cates J, Tannenbaum A. Automatic segmentation of the left atrium from MRI images using salient feature and contour evolution. Conf Proc IEEE Eng Med Biol Soc. 2012;2012 :3211-4.Abstract
We propose an automatic approach for segmenting the left atrium from MRI images. In particular, the thoracic aorta is detected and used as a salient feature to find a seed region that lies inside the left atrium. A hybrid energy that combines robust statistics and localized region intensity information is employed to evolve active contours from the seed region to capture the whole left atrium. The experimental results demonstrate the accuracy and robustness of our approach.
Pasternak O, Shenton ME, Westin C-F. Estimation of extracellular volume from regularized multi-shell diffusion MRI. Med Image Comput Comput Assist Interv. 2012;15 (Pt 2) :305-12.Abstract
Diffusion MRI measures micron scale displacement of water molecules, providing unique insight into microstructural tissue architecture. However, current practical image resolution is in the millimeter scale, and thus diffusivities from many tissue compartments are averaged in each voxel, reducing the sensitivity and specificity of the measurement to subtle pathologies. Recent studies have pointed out that eliminating the contribution of extracellular water increases the sensitivity of the diffusion measures to tissue architecture. Moreover, in brain imaging, estimation of the extracellular volume appears to indicate pathological processes such as atrophy, edema and neuroinflammation. Here we study the free-water method, which assumes a bi-tensor model. We add low b-value shells to a regular DTI acquisition and present methods to improve the estimation of the model parameters using the extra information. In addition, we define a Laplace-Beltrami regularization operator that further stabilizes the multi-shell estimation.
Toews M, Wells III WM, Zöllei L. A Feature-based Developmental Model of the Infant Brain in Structural MRI. Med Image Comput Comput Assist Interv. 2012;15 (Pt 2) :204-11.Abstract

In this paper, anatomical development is modeled as a collection of distinctive image patterns localized in space and time. A Bayesian posterior probability is defined over a random variable of subject age, conditioned on data in the form of scale-invariant image features. The model is automatically learned from a large set of images exhibiting significant variation, used to discover anatomical structure related to age and development, and fit to new images to predict age. The model is applied to a set of 230 infant structural MRIs of 92 subjects acquired at multiple sites over an age range of 8-590 days. Experiments demonstrate that the model can be used to identify age-related anatomical structure, and to predict the age of new subjects with an average error of 72 days.

Savadjiev P, Rathi Y, Bouix S, Verma R, Westin C-F. Multi-scale characterization of white matter tract geometry. Med Image Comput Comput Assist Interv. 2012;15 (Pt 3) :34-41.Abstract
The geometry of white matter tracts is of increased interest for a variety of neuroscientific investigations, as it is a feature reflective of normal neurodevelopment and disease factors that may affect it. In this paper, we introduce a novel method for computing multi-scale fibre tract shape and geometry based on the differential geometry of curve sets. By measuring the variation of a curve's tangent vector at a given point in all directions orthogonal to the curve, we obtain a 2D "dispersion distribution function" at that point. That is, we compute a function on the unit circle which describes fibre dispersion, or fanning, along each direction on the circle. Our formulation is then easily incorporated into a continuous scale-space framework. We illustrate our method on different fibre tracts and apply it to a population study on hemispheric lateralization in healthy controls. We conclude with directions for future work.
Gholami B, Norton I, Tannenbaum AR, Agar NYR. Recursive feature elimination for brain tumor classification using desorption electrospray ionization mass spectrometry imaging. Conf Proc IEEE Eng Med Biol Soc. 2012;2012 :5258-61.Abstract
The metabolism and composition of lipids is of increasing interest for understanding and detecting disease processes. Lipid signatures of tumor type and grade have been demonstrated using magnetic resonance spectroscopy. Clinical management and ultimate prognosis of brain tumors depend largely on the tumor type, subtype, and grade. Mass spectrometry, a well-known analytical technique used to identify molecules in a given sample based on their mass, can significantly improve the problem of tumor type classification. This work focuses on the problem of identifying lipid features to use as input for classification. Feature selection could result in improvements in classifier performance, discovery of biomarkers, improved data interpretation, and patient treatment.
Risholm P, Janoos F, Pursley J, Fedorov A, Tempany CM, Cormack RA, Wells III WM. Selection of Optimal Hyper-Parameters for Estimation of Uncertainty in MRI-TRUS Registration of the Prostate. Med Image Comput Comput Assist Interv. 2012;15 (Pt 3) :107-14.Abstract

Transrectal ultrasound (TRUS) facilitates intra-treatment delineation of the prostate gland (PG) to guide insertion of brachytherapy seeds, but the prostate substructure and apex are not always visible which may make the seed placement sub-optimal. Based on an elastic model of the prostate created from MRI, where the prostate substructure and apex are clearly visible, we use a Bayesian approach to estimate the posterior distribution on deformations that aligns the pre-treatment MRI with intra-treatment TRUS. Without apex information in TRUS, the posterior prediction of the location of the prostate boundary, and the prostate apex boundary in particular, is mainly determined by the pseudo stiffness hyper-parameter of the prior distribution. We estimate the optimal value of the stiffness through likelihood maximization that is sensitive to the accuracy as well as the precision of the posterior prediction at the apex boundary. From a data-set of 10 pre- and intra-treatment prostate images with ground truth delineation of the total PG, 4 cases were used to establish an optimal stiffness hyper-parameter when 15% of the prostate delineation was removed to simulate lack of apex information in TRUS, while the remaining 6 cases were used to cross-validate the registration accuracy and uncertainty over the PG and in the apex.

Wachinger C, Golland P. Spectral label fusion. Med Image Comput Comput Assist Interv. 2012;15 (Pt 3) :410-7.Abstract
We present a new segmentation approach that combines the strengths of label fusion and spectral clustering. The result is an atlas-based segmentation method guided by contour and texture cues in the test image. This offers advantages for datasets with high variability, making the segmentation less prone to registration errors. We achieve the integration by letting the weights of the graph Laplacian depend on image data, as well as atlas-based label priors. The extracted contours are converted to regions, arranged in a hierarchy depending on the strength of the separating boundary. Finally, we construct the segmentation by a region-wise, instead of voxel-wise, voting, increasing the robustness. Our experiments on cardiac MRI show a clear improvement over majority voting and intensity-weighted label fusion.

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