Publications

2012
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.
O'Donnell LJ, Wells WM, Golby AJ, Westin C-F. Unbiased groupwise registration of white matter tractography. Med Image Comput Comput Assist Interv. 2012;15 (Pt 3) :123-30.Abstract
We present what we believe to be the first investigation into unbiased multi-subject registration of whole brain diffusion tractography of the white matter. To our knowledge, this is also the first entropy-based objective function applied to fiber tract registration. To define the probability of fiber trajectories for the computation of entropy, we take advantage of a pairwise fiber distance used as the basis for a Gaussian-like kernel. By employing several values of the kernel's scale parameter, the method is inherently multi-scale. Results of experiments using synthetic and real datasets demonstrate the potential of the method for simultaneous joint registration of tractography.
Gholami B, Bailey JM, Haddad WM, Tannenbaum AR. Clinical Decision Support and Closed-Loop Control for Cardiopulmonary Management and Intensive Care Unit Sedation Using Expert Systems. IEEE Trans Control Syst Technol. 2012;20 (5) :1343-1350.Abstract
Patients in the intensive care unit (ICU) who require mechanical ventilation due to acute respiratory failure also frequently require the administration of sedative agents. The need for sedation arises both from patient anxiety due to the loss of personal control and the unfamiliar and intrusive environment of the ICU, and also due to pain or other variants of noxious stimuli. While physicians select the agent(s) used for sedation and cardiovascular function, the actual administration of these agents is the responsibility of the nursing staff. If clinical decision support systems and closed-loop control systems could be developed for critical care monitoring and lifesaving interventions as well as the administration of sedation and cardiopulmonary management, the ICU nurse could be released from the intense monitoring of sedation, allowing her/him to focus on other critical tasks. One particularly attractive strategy is to utilize the knowledge and experience of skilled clinicians, capturing explicitly the rules expert clinicians use to decide on how to titrate drug doses depending on the level of sedation. In this paper, we extend the deterministic rule-based expert system for cardiopulmonary management and ICU sedation framework presented in [1] to a stochastic setting by using probability theory to quantify uncertainty and hence deal with more realistic clinical situations.
Fedorov A, Tuncali K, Fennessy FM, Tokuda J, Hata N, Wells WM, Kikinis R, Tempany CM. Image Registration for Targeted MRI-guided Transperineal Prostate Biopsy. J Magn Reson Imaging. 2012;36 (4) :987-92.Abstract

PURPOSE: To develop and evaluate image registration methodology for automated re-identification of tumor-suspicious foci from preprocedural MR exams during MR-guided transperineal prostate core biopsy. MATERIALS AND METHODS: A hierarchical approach for automated registration between planning and intra-procedural T2-weighted prostate MRI was developed and evaluated on the images acquired during 10 consecutive MR-guided biopsies. Registration accuracy was quantified at image-based landmarks and by evaluating spatial overlap for the manually segmented prostate and sub-structures. Registration reliability was evaluated by simulating initial mis-registration and analyzing the convergence behavior. Registration precision was characterized at the planned biopsy targets. RESULTS: The total computation time was compatible with a clinical setting, being at most 2 min. Deformable registration led to a significant improvement in spatial overlap of the prostate and peripheral zone contours compared with both rigid and affine registration. Average in-slice landmark registration error was 1.3 ± 0.5 mm. Experiments simulating initial mis-registration resulted in an estimated average capture range of 6 mm and an average in-slice registration precision of ±0.3 mm. CONCLUSION: Our registration approach requires minimum user interaction and is compatible with the time constraints of our interventional clinical workflow. The initial evaluation shows acceptable accuracy, reliability and consistency of the method.

2011
Kapur T, Tempany CM, Jolesz FA. Proceedings of the 4th Image Guided Therapy Workshop. 2011;4 :1-121. 2011 IGT Workshop Proceedings
Moscufo N, Guttmann CRG, Meier D, Csapo I, Hildenbrand PG, Healy BC, Schmidt JA, Wolfson L. Brain regional lesion burden and impaired mobility in the elderly. Neurobiol Aging. 2011;32 (4) :646-54.Abstract
This study investigated the relationship of brain white matter (WM) lesions affecting specific neural networks with decreased mobility in ninety-nine healthy community-dwelling subjects ≥75 years old prospectively enrolled by age and mobility status. We assessed lesion burden in the genu, body and splenium of corpus callosum; anterior, superior and posterior corona radiata; anterior and posterior limbs of internal capsule; corticospinal tract; and superior longitudinal fasciculus. Burden in the splenium of corpus callosum (SCC) demonstrated the highest correlation particularly with walking speed (r=0.4, p<10(-4)), and in logistic regression it was the best regional predictor of low mobility performance. We also found that independent of mobility, corona radiata has the largest lesion burden with anterior (ACR) and posterior (PCR) aspects being the most frequently affected. The results suggest that compromised inter-hemispheric integration of visuospatial information through the SCC plays an important role in mobility impairment in the elderly. The relatively high lesion susceptibility of ACR and PCR in all subjects may obscure the importance of these lesions in mobility impairment.
Langs G, Menze BH, Lashkari D, Golland P. Detecting stable distributed patterns of brain activation using Gini contrast. Neuroimage. 2011;56 (2) :497-507.Abstract
The relationship between spatially distributed fMRI patterns and experimental stimuli or tasks offers insights into cognitive processes beyond those traceable from individual local activations. The multivariate properties of the fMRI signals allow us to infer interactions among individual regions and to detect distributed activations of multiple areas. Detection of task-specific multivariate activity in fMRI data is an important open problem that has drawn much interest recently. In this paper, we study and demonstrate the benefits of random forest classifiers and the associated Gini importance measure for selecting voxel subsets that form a multivariate neural response. The Gini importance measure quantifies the predictive power of a particular feature when considered as part of the entire pattern. The measure is based on a random sampling of fMRI time points and voxels. As a consequence the resulting voxel score, or Gini contrast, is highly reproducible and reliably includes all informative features. The method does not rely on a priori assumptions about the signal distribution, a specific statistical or functional model or regularization. Instead, it uses the predictive power of features to characterize their relevance for encoding task information. The Gini contrast offers an additional advantage of directly quantifying the task-relevant information in a multiclass setting, rather than reducing the problem to several binary classification subproblems. In a multicategory visual fMRI study, the proposed method identified informative regions not detected by the univariate criteria, such as the t-test or the F-test. Including these additional regions in the feature set improves the accuracy of multicategory classification. Moreover, we demonstrate higher classification accuracy and stability of the detected spatial patterns across runs than the traditional methods such as the recursive feature elimination used in conjunction with support vector machines.
Sandhu R, Dambreville S, Yezzi A, Tannenbaum A. A nonrigid kernel-based framework for 2D-3D pose estimation and 2D image segmentation. IEEE Trans Pattern Anal Mach Intell. 2011;33 (6) :1098-115.Abstract
In this work, we present a nonrigid approach to jointly solving the tasks of 2D-3D pose estimation and 2D image segmentation. In general, most frameworks that couple both pose estimation and segmentation assume that one has exact knowledge of the 3D object. However, under nonideal conditions, this assumption may be violated if only a general class to which a given shape belongs is given (e.g., cars, boats, or planes). Thus, we propose to solve the 2D-3D pose estimation and 2D image segmentation via nonlinear manifold learning of 3D embedded shapes for a general class of objects or deformations for which one may not be able to associate a skeleton model. Thus, the novelty of our method is threefold: first, we present and derive a gradient flow for the task of nonrigid pose estimation and segmentation. Second, due to the possible nonlinear structures of one's training set, we evolve the pre-image obtained through kernel PCA for the task of shape analysis. Third, we show that the derivation for shape weights is general. This allows us to use various kernels, as well as other statistical learning methodologies, with only minimal changes needing to be made to the overall shape evolution scheme. In contrast with other techniques, we approach the nonrigid problem, which is an infinite-dimensional task, with a finite-dimensional optimization scheme. More importantly, we do not explicitly need to know the interaction between various shapes such as that needed for skeleton models as this is done implicitly through shape learning. We provide experimental results on several challenging pose estimation and segmentation scenarios.

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