Gautam Prasad

Online Resource for Validation of Brain Segmentation Methods

One key issue that must be addressed during the development of image segmentation algorithms is the accuracy of the results they produce. Algorithm developers require this so they can see where methods need to be improved and see how new developments compare with existing ones. Users of algorithms also need to understand the characteristics of algorithms when they select and apply them to their neuroimaging analysis applications. Many metrics have been proposed to characterize error and success rates in segmentation, and several datasets have also been made public for evaluation. Still, the methodologies used in analyzing and reporting these results vary from study to study, so even when studies use the same metrics their numerical results may not necessarily be directly comparable. To address this problem, we developed a web-based resource for evaluating the performance of skull-stripping in T1-weighted MRI. The resource provides both the data to be segmented and an online application that performs a validation study on the data. Users may download the test dataset, segment it using whichever method they wish to assess, and upload their segmentation results to the server. The server computes a series of metrics, displays a detailed report of the validation results, and archives these for future browsing and analysis. We applied this framework to the evaluation of 3 popular skull-stripping algorithms--the Brain Extraction Tool [Smith, S.M., 2002. Fast robust automated brain extraction. Hum. Brain Mapp. 17 (3),143-155 (Nov)], the Hybrid Watershed Algorithm [Ségonne, F., Dale, A.M., Busa, E., Glessner, M., Salat, D., Hahn, H.K., Fischl, B., 2004. A hybrid approach to the skull stripping problem in MRI. NeuroImage 22 (3), 1060-1075 (Jul)], and the Brain Surface Extractor [Shattuck, D.W., Sandor-Leahy, S.R., Schaper, K.A., Rottenberg, D.A., Leahy, R.M., 2001. Magnetic resonance image tissue classification using a partial volume model. NeuroImage 13 (5), 856-876 (May) under several different program settings. Our results show that with proper parameter selection, all 3 algorithms can achieve satisfactory skull-stripping on the test data.

Tractography density and network measures in Alzheimer'S disease

Brain connectivity declines in Alzheimers disease (AD), both functionally and structurally. Connectivity maps and networks derived from diffusion-based tractography offer new ways to track disease progression and to understand how AD affects the brain. Here we set out to identify (1) which fiber network measures show greatest differences between AD patients and controls, and (2) how these effects depend on the density of fibers extracted by the tractography algorithm. We computed brain networks from diffusion-weighted images (DWI) of the brain, in 110 subjects (28 normal elderly, 56 with early and 11 with late mild cognitive impairment, and 15 with AD). We derived connectivity matrices and network topology measures, for each subject, from whole-brain tractography and cortical parcellations. We used an ODF lookup table to speed up fiber extraction, and to exploit the full information in the orientation distribution function (ODF). This made it feasible to compute high density connectivity maps. We used accelerated tractography to compute a large number of fibers to understand what effect fiber density has on network measures and in distinguishing different disease groups in our data. We focused on global efficiency, transitivity, path length, mean degree, density, modularity, small world, and assortativity measures computed from weighted and binary undirected connectivity matrices. Of all these measures, the mean nodal degree best distinguished diagnostic groups. High-density fiber matrices were most helpful for picking up the more subtle clinical differences, e.g. between mild cognitively impaired (MCI) and normals, or for distinguishing subtypes of MCI (early versus late). Care is needed in clinical analyses of brain connectivity, as the density of extracted fibers may affect how well a network measure can pick up differences between patients and controls.

Atlas-based fiber clustering for multi-subject analysis of high angular resolution diffusion imaging tractography

High angular resolution diffusion imaging (HARDI) allows in vivo analysis of the white matter structure and connectivity. Based on orientation distribution functions (ODFs) that represent the directionality of water diffusion at each point in the brain, tractography methods can recover major axonal pathways. This enables tract-based analysis of fiber integrity and connectivity. For multi-subject comparisons, fibers may be clustered into bundles that are consistently found across subjects. To do this, we scanned 20 young adults with HARDI at 4 T. From the reconstructed ODFs, we performed whole-brain tractography with a novel Hough transform method. We then used measures of agreement between the extracted 3D curves and a co-registered probabilistic DTI atlas to select key pathways. Using median filtering and a shortest path graph search, we derived the maximum density path to compactly represent each tract in the population. With this tract-based method, we performed tract-based analysis of fractional anisotropy, and assessed how the chosen tractography algorithm influenced the results. The resulting method may expedite population-based statistical analysis of HARDI and DTI.

Genetics of path lengths in brain connectivity networks: HARDI-Based maps in 457 adults

Brain connectivity analyses are increasingly popular for investigating organization. Many connectivity measures including path lengths are generally defined as the number of nodes traversed to connect a node in a graph to the others. Despite its name, path length is purely topological, and does not take into account the physical length of the connections. The distance of the trajectory may also be highly relevant, but is typically overlooked in connectivity analyses. Here we combined genotyping, anatomical MRI and HARDI to understand how our genes influence the cortical connections, using whole-brain tractography. We defined a new measure, based on Dijkstras algorithm, to compute path lengths for tracts connecting pairs of cortical regions. We compiled these measures into matrices where elements represent the physical distance traveled along tracts. We then analyzed a large cohort of healthy twins and show that our path length measure is reliable, heritable, and influenced even in young adults by the Alzheimers risk gene, CLU.

A Dynamical Clustering Model of Brain Connectivity Inspired by the N-Body Problem

We present a method for studying brain connectivity by simulating a dynamical evolution of the nodes of the network. The nodes are treated as particles, and evolved under a simulated force analogous to gravitational acceleration in the well-known N -body problem. The particle nodes correspond to regions of the cortex. The locations of particles are defined as the centers of the respective regions on the cortex and their masses are proportional to each regions volume. The force of attraction is modeled on the gravitational force, and explicitly made proportional to the elements of a connectivity matrix derived from diffusion imaging data. We present experimental results of the simulation on a population of 110 subjects from the Alzheimers Disease Neuroimaging Initiative (ADNI), consisting of healthy elderly controls, early mild cognitively impaired (eMCI), late MCI (LMCI), and Alzheimers disease (AD) patients. Results show significant differences in the dynamic properties of connectivity networks in healthy controls, compared to eMCI as well as AD patients.

Estimating Uncertainty in Brain Region Delineations

This paper presents a method for estimating uncertainty in MRI-based brain region delineations provided by fully-automated segmentation methods. In large data sets, the uncertainty estimates could be used to detect fully-automated method failures, identify low-quality imaging data, or endow downstream statistical analyses with per-subject uncertainty in derived morphometric measures. Region segmentation is formulated in a statistical inference framework; the probability that a given region-delineating surface accounts for observed image data is quantified by a distribution that takes into account a prior model of plausible region shape and a model of how the region appears in images. Region segmentation consists of finding the maximum a posteriori (MAP) parameters of the delineating surface under this distribution, and segmentation uncertainty is quantified in terms of how sharply peaked the distribution is in the vicinity of the maximum. Uncertainty measures are estimated through Markov Chain Monte Carlo (MCMC) sampling of the distribution in the vicinity of the MAP estimate. Experiments on real and synthetic data show that the uncertainty measures automatically detect when the delineating surface of the entire brain is unclear due to poor image quality or artifact; the experiments cover multiple appearance models to demonstrate the generality of the method. The approach is also general enough to accommodate a wide range of shape models and brain regions.

Flow-based network measures of brain connectivity in Alzheimer'S disease

We present a new flow-based method for modeling brain structural connectivity. The method uses a modified maximum-flow algorithm that is robust to noise in the diffusion data and guided by biologically viable pathways and structure of the brain. A flow network is first created using a lattice graph by connecting all lattice points (voxel centers) to all their neighbors by edges. Edge weights are based on the orientation distribution function (ODF) value in the direction of the edge. The maximum-flow is computed based on this flow graph using the flow or the capacity between each region of interest (ROI) pair by following the connected tractography fibers projected onto the flow graph edges. Network measures such as global efficiency, transitivity, path length, mean degree, density, modularity, small world, and assortativity are computed from the flow connectivity matrix. We applied our method to diffusion-weighted images (DWIs) from 110 subjects (28 normal elderly, 56 with early and 11 with late mild cognitive impairment, and 15 with AD) and segmented co-registered anatomical MRIs into cortical regions. Experimental results showed better performance compared to the standard fiber-counting methods when distinguishing Alzheimers disease from normal aging.

Skull-stripping with deformable organisms

Segmenting brain from non-brain tissue within magnetic resonance (MR) images of the human head, also known as skull-stripping, is a critical processing step in the analysis of neuroimaging data. Though many algorithms have been developed to address this problem, challenges remain. In this paper, we apply the “deformable organism” framework to the skull-stripping problem. Within this framework, deformable models are equipped with higher-level control mechanisms based on the principles of artificial life, including sensing, reactive behavior, knowledge representation, and proactive planning. Our new deformable organisms are governed by a high-level plan aimed at the fully-automated segmentation of various parts of the head in MR imagery, and they are able to cooperate in computing a robust and accurate segmentation. We applied our segmentation approach to a test set of human MRI data using manual delineations of the data as a reference “gold standard.” We compare these results with results from three widely used methods using set-similarity metrics.

Using the raw diffusion MRI signal and the von Mises-Fisher distribution for classification of Alzheimer's disease.

Diffusion MRI (dMRI) offers new signals for disease classification not available using standard anatomical MRI. However, most studies transform the raw signal to a parametric model before extracting features for classification. Here, we employ a novel method that models the signal directly to extract features for classification of Alzheimers disease (AD) patients versus healthy controls (HC). We studied 38 AD patients and 51 HC from the Alzheimers Disease Neuroimaging Initiative, and evaluated the effectiveness of two sets of features for a logistic regression classifier: (1) coefficients from a mixture of von Mises-Fisher (vMF) distributions with fixed mean directions, and (2) coefficients from a spherical harmonic (SH) expansion. We compared the classification performance for these methods with that of fractional anisotropy (FA), a popular scalar metric used in dMRI. We found vMF, SH and FA features achieved mean accuracies of 86.9%, 85.6% and 76.4% respectively, suggesting benefits of “beyond-tensor” diffusion models.

7T Multi-shell Hybrid Diffusion Imaging (HYDI) for Mapping Brain Connectivity in Mice

Diffusion weighted imaging (DWI) is widely used to study microstructural characteristics of the brain. High angular resolution diffusion imaging (HARDI) samples diffusivity at a large number of spherical angles, to better resolve neural fibers that mix or cross. Here, we implemented a framework for advanced mathematical analysis of mouse 5-shell HARDI (b=1000, 3000, 4000, 8000, 12000 s/mm2), also known as hybrid diffusion imaging (HYDI). Using q-ball imaging (QBI) at ultra-high field strength (7 Tesla), we computed diffusion and fiber orientation distribution functions (dODF, fODF) to better detect crossing fibers. We also computed a quantitative anisotropy (QA) index, and deterministic tractography, from the peak orientation of the fODFs. We found that the signal to noise ratio (SNR) of the QA was significantly higher in single and multi-shell reconstructed data at the lower b-values (b=1000, 3000, 4000 s/mm2) than at higher b-values (b=8000, 12000 s/mm2); the b=1000 s/mm2 shell increased the SNR of the QA in all multi-shell reconstructions, but when used alone or in <5-shell reconstruction, it led to higher angular error for the major fibers, compared to 5-shell HYDI. Multi-shell data reconstructed major fibers with less error than single-shell data, and was most successful at reducing the angular error when the lowest shell was excluded (b=1000 s/mm2). Overall, high-resolution connectivity mapping with 7T HYDI offers great potential for understanding unresolved changes in mouse models of brain disease.