Publications

2012

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. Nineteen of 25 (76%) malignant SPNs showed 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.
Chen GH, Fedorenko EG, Kanwisher NG, Golland P. Deformation-Invariant Sparse Coding for Modeling Spatial Variability of Functional Patterns in the Brain. Mach Learn Interpret Neuroimaging (2011). 2012;7263:68–75.
For a given cognitive task such as language processing, the location of corresponding functional regions in the brain may vary across subjects relative to anatomy. We present a probabilistic generative model that accounts for such variability as observed in fMRI data. We relate our approach to sparse coding that estimates a basis consisting of functional regions in the brain. Individual fMRI data is represented as a weighted sum of these functional regions that undergo deformations. We demonstrate the proposed method on a language fMRI study. Our method identified activation regions that agree with known literature on language processing and established correspondences among activation regions across subjects, producing more robust group-level effects than anatomical alignment alone.
Donnell LJO, Rigolo L, Norton I, Wells WM, Westin CF, Golby AJ. fMRI-DTI modeling via landmark distance atlases for prediction and detection of fiber tracts. Neuroimage. 2012;60(1):456–70.
The overall goal of this research is the design of statistical atlas models that can be created from normal subjects, but may generalize to be applicable to abnormal brains. We present a new style of joint modeling of fMRI, DTI, and structural MRI. Motivated by the fact that a white matter tract and related cortical areas are likely to displace together in the presence of a mass lesion (brain tumor), in this work we propose a rotation and translation invariant model that represents the spatial relationship between fiber tracts and anatomic and functional landmarks. This landmark distance model provides a new basis for representation of fiber tracts and can be used for detection and prediction of fiber tracts based on landmarks. Our results indicate that the measured model is consistent across normal subjects, and thus suitable for atlas building. Our experiments demonstrate that the model is robust to displacement and missing data, and can be successfully applied to a small group of patients with mass lesions.
Tristan-Vega A, García-Pérez V, Aja-Fernández S, Westin CF. Efficient and robust nonlocal means denoising of MR data based on salient features matching. Comput Methods Programs Biomed. 2012;105(2):131–44.
The nonlocal means (NLM) filter has become a popular approach for denoising medical images due to its excellent performance. However, its heavy computational load has been an important shortcoming preventing its use. NLM works by averaging pixels in nonlocal vicinities, weighting them depending on their similarity with the pixel of interest. This similarity is assessed based on the squared difference between corresponding pixels inside local patches centered at the locations compared. Our proposal is to reduce the computational load of this comparison by checking only a subset of salient features associated to the pixels, which suffice to estimate the actual difference as computed in the original NLM approach. The speedup achieved with respect to the original implementation is over one order of magnitude, and, when compared to more recent NLM improvements for MRI denoising, our method is nearly twice as fast. At the same time, we evidence from both synthetic and in vivo experiments that computing of appropriate salient features make the estimation of NLM weights more robust to noise. Consequently, we are able to improve the outcomes achieved with recent state of the art techniques for a wide range of realistic Signal-to-Noise ratio scenarios like diffusion MRI. Finally, the statistical characterization of the features computed allows to get rid of some of the heuristics commonly used for parameter tuning.
Venkataraman A, Rathi Y, Kubicki M, Westin CF, Golland P. Joint modeling of anatomical and functional connectivity for population studies. IEEE Trans Med Imaging. 2012;31(2):164–82.
We propose a novel probabilistic framework to merge information from diffusion weighted imaging tractography and resting-state functional magnetic resonance imaging correlations to identify connectivity patterns in the brain. In particular, we model the interaction between latent anatomical and functional connectivity and present an intuitive extension to population studies. We employ the EM algorithm to estimate the model parameters by maximizing the data likelihood. The method simultaneously infers the templates of latent connectivity for each population and the differences in connectivity between the groups. We demonstrate our method on a schizophrenia study. Our model identifies significant increases in functional connectivity between the parietal/posterior cingulate region and the frontal lobe and reduced functional connectivity between the parietal/posterior cingulate region and the temporal lobe in schizophrenia. We further establish that our model learns predictive differences between the control and clinical populations, and that combining the two modalities yields better results than considering each one in isolation.
Lashkari D, Sridharan R, Vul E, Hsieh PJ, Kanwisher N, Golland P. Search for patterns of functional specificity in the brain: a nonparametric hierarchical Bayesian model for group fMRI data. Neuroimage. 2012;59(2):1348–68.
Functional MRI studies have uncovered a number of brain areas that demonstrate highly specific functional patterns. In the case of visual object recognition, small, focal regions have been characterized with selectivity for visual categories such as human faces. In this paper, we develop an algorithm that automatically learns patterns of functional specificity from fMRI data in a group of subjects. The method does not require spatial alignment of functional images from different subjects. The algorithm is based on a generative model that comprises two main layers. At the lower level, we express the functional brain response to each stimulus as a binary activation variable. At the next level, we define a prior over sets of activation variables in all subjects. We use a Hierarchical Dirichlet Process as the prior in order to learn the patterns of functional specificity shared across the group, which we call functional systems, and estimate the number of these systems. Inference based on our model enables automatic discovery and characterization of dominant and consistent functional systems. We apply the method to data from a visual fMRI study comprised of 69 distinct stimulus images. The discovered system activation profiles correspond to selectivity for a number of image categories such as faces, bodies, and scenes. Among systems found by our method, we identify new areas that are deactivated by face stimuli. In empirical comparisons with previously proposed exploratory methods, our results appear superior in capturing the structure in the space of visual categories of stimuli.
Gadde S, Aucoin N, Grethe JS, Keator DB, Marcus DS, Pieper S. XCEDE: an extensible schema for biomedical data. Neuroinformatics. 2012;10(1):19–32.
The XCEDE (XML-based Clinical and Experimental Data Exchange) XML schema, developed by members of the BIRN (Biomedical Informatics Research Network), provides an extensive metadata hierarchy for storing, describing and documenting the data generated by scientific studies. Currently at version 2.0, the XCEDE schema serves as a specification for the exchange of scientific data between databases, analysis tools, and web services. It provides a structured metadata hierarchy, storing information relevant to various aspects of an experiment (project, subject, protocol, etc.). Each hierarchy level also provides for the storage of data provenance information allowing for a traceable record of processing and/or changes to the underlying data. The schema is extensible to support the needs of various data modalities and to express types of data not originally envisioned by the developers. The latest version of the XCEDE schema and manual are available from http://www.xcede.org/ .