Publications by Year: 2012


Shenton ME, Hamoda HM, Schneiderman JS, Bouix S, Pasternak O, Rathi Y, Vu MA, Purohit MP, Helmer KG, Koerte IK, Lin AP, Westin CF, Kikinis R, Kubicki M, Stern RA, Zafonte R. A Review of Magnetic Resonance Imaging and Diffusion Tensor Imaging Findings in Mild Traumatic Brain Injury. Brain Imaging Behav. 2012;6(2):137–92.
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.
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.
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 JC, Pujol S, Bauer C, Jennings D, Fennessy F, Sonka M, Buatti J, Aylward S, Miller J V, Pieper S, Kikinis R. 3D Slicer as an image computing platform for the Quantitative Imaging Network. Magn Reson Imaging. 2012;30(9):1323–41.
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.
Nakhmani A, Tannenbaum A. Self-crossing Detection and Location for Parametric active Contours. IEEE Trans Image Process. 2012;21(7):3150–6.
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.
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.
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, Tristan-Vega A, Aja-Fernández S, Alberola-López C, Westin CF, Estepar RSJ. Optimal real-time estimation in diffusion tensor imaging. Magn Reson Imaging. 2012;30(4):506–17.
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.
Mamata H, Tokuda J, Gill RR, Padera RF, Lenkinski RE, Sugarbaker DJ, Butler JP, Hatabu H. Clinical application of pharmacokinetic analysis as a biomarker of solitary pulmonary nodules: dynamic contrast-enhanced MR imaging. Magn Reson Med. 2012;68(5):1614–22.
The purpose of this study is to evaluate perfusion indices and pharmacokinetic parameters in solitary pulmonary nodules (SPNs). Thirty patients of 34 enrolled with SPNs (15-30 mm) were evaluated in this study. T1 and T2-weighted structural images and 2D turbo FLASH perfusion images were acquired with shallow free breathing. B-spline nonrigid image registration and optimization by χ² test against pharmacokinetic model curve were performed on dynamic contrast-enhanced MRI. This allowed voxel-by-voxel calculation of k(ep) , the rate constant for tracer transport to and from plasma and the extravascular extracellular space. Mean transit time, time-to-peak, initial slope, and maximum enhancement (E(max) ) were calculated from time-intensity curves fitted to a gamma variate function. After blinded data analysis, correlation with tissue histology from surgical resection or biopsy samples was performed. Histologic evaluation revealed 25 malignant and five benign SPNs. All benign SPNs had k(ep) 1.0 min$^-$¹. Sensitivity to diagnose malignant SPNs at a cutoff of k(ep) = 1.0 min$^-$¹ was 76%, specificity was 100%, positive predictive value was 100%, negative predictive value was 45%, and accuracy was 80%. Of all indices studied, k(ep) was the most significant in differentiating malignant from benign SPNs.
Tristan-Vega A, Aja-Fernández S, Westin CF. Least squares for diffusion tensor estimation revisited: propagation of uncertainty with Rician and non-Rician signals. Neuroimage. 2012;59(4):4032–43.
Least Squares (LS) and its minimum variance counterpart, Weighted Least Squares (WLS), have become very popular when estimating the Diffusion Tensor (DT), to the point that they are the standard in most of the existing software for diffusion MRI. They are based on the linearization of the Stejskal-Tanner equation by means of the logarithmic compression of the diffusion signal. Due to the Rician nature of noise in traditional systems, a certain bias in the estimation is known to exist. This artifact has been made patent through some experimental set-ups, but it is not clear how the distortion translates in the reconstructed DT, and how important it is when compared to the other source of error contributing to the Mean Squared Error (MSE) in the estimate, i.e. the variance. In this paper we propose the analytical characterization of log-Rician noise and its propagation to the components of the DT through power series expansions. We conclude that even in highly noisy scenarios the bias for log-Rician signals remains moderate when compared to the corresponding variance. Yet, with the advent of Parallel Imaging (pMRI), the Rician model is not always valid. We make our analysis extensive to a number of modern acquisition techniques through the study of a more general Non Central-Chi (nc-χ) model. Since WLS techniques were initially designed bearing in mind Rician noise, it is not clear whether or not they still apply to pMRI. An important finding in our work is that the common implementation of WLS is nearly optimal when nc-χ noise is considered. Unfortunately, the bias in the estimation becomes far more important in this case, to the point that it may nearly overwhelm the variance in given situations. Furthermore, we evidence that such bias cannot be removed by increasing the number of acquired gradient directions. A number of experiments have been conducted that corroborate our analytical findings, while in vivo data have been used to test the actual relevance of the bias in the estimation.
Gao Y, Corn B, Schifter D, Tannenbaum A. Multiscale 3D shape representation and segmentation with applications to hippocampal/caudate extraction from brain MRI. Med Image Anal. 2012;16(2):374–85.
Extracting structure of interest from medical images is an important yet tedious work. Due to the image quality, the shape knowledge is widely used for assisting and constraining the segmentation process. In many previous works, shape knowledge was incorporated by first constructing a shape space from training cases, and then constraining the segmentation process to be within the learned shape space. However, such an approach has certain limitations due to the number of variations, eigen-shapemodes, that can be captured in the learned shape space. Moreover, small scale shape variances are usually overwhelmed by those in the large scale, and therefore the local shape information is lost. In this work, we present a multiscale representation for shapes with arbitrary topology, and a fully automatic method to segment the target organ/tissue from medical images using such multiscale shape information and local image features. First, we handle the problem of lacking eigen-shapemodes by providing a multiscale shape representation using the wavelet transform. Consequently, the shape variances existing in the training shapes captured by the statistical learning step are also represented at various scales. Note that by doing so, one can greatly enrich the eigen-shapemodes as well as capture small scale shape changes. Furthermore, in order to make full use of the training information, not only the shape but also the grayscale training images are utilized in a multi-atlas initialization procedure. By combining such initialization with the multiscale shape knowledge, we perform segmentation tests for challenging medical data sets where the target objects have low contrast and sharp corner structures, and demonstrate the statistically significant improvement obtained by employing such multiscale representation, in representing shapes as well as the overall shape based segmentation tasks.
Rosenberger G, Nestor PG, Oh JS, Levitt JJ, Kindleman G, Bouix S, Fitzsimmons J, Niznikiewicz M, Westin CF, Kikinis R, McCarley RW, Shenton ME, Kubicki M. Anterior limb of the internal capsule in schizophrenia: a diffusion tensor tractography study. Brain Imaging Behav. 2012;6(3):417–25.
Thalamo-cortical feedback loops play a key role in the processing and coordination of processing and integration of perceptual inputs and outputs, and disruption in this connection has long been hypothesized to contribute significantly to neuropsychological disturbances in schizophrenia. To test this hypothesis, we applied diffusion tensor tractography to 18 patients suffering schizophrenia and 20 control subjects. Fractional anisotropy (FA) was evaluated in the bilateral anterior and posterior limbs of the internal capsule, and correlated with clinical and neurocognitive measures. Patients diagnosed with schizophrenia showed significantly reduced FA bilaterally in the anterior but not the posterior limb of the internal capsule, compared with healthy control subjects. Lower FA correlated with lower scores on tests of declarative episodic memory in the patient group only. These findings suggest that disruptions, bilaterally, in thalamo-cortical connections in schizophrenia may contribute to disease-related impairment in the coordination of mnemonic processes of encoding and retrieval that are vital for efficient learning of new information.