David W. Shattuck

Magnetic Resonance Image Tissue Classification Using a Partial Volume Model

We describe a sequence of low-level operations to isolate and classify brain tissue within T1-weighted magnetic resonance images (MRI). Our method first removes nonbrain tissue using a combination of anisotropic diffusion filtering, edge detection, and mathematical morphology. We compensate for image nonuniformities due to magnetic field inhomogeneities by fitting a tricubic B-spline gain field to local estimates of the image nonuniformity spaced throughout the MRI volume. The local estimates are computed by fitting a partial volume tissue measurement model to histograms of neighborhoods about each estimate point. The measurement model uses mean tissue intensity and noise variance values computed from the global image and a multiplicative bias parameter that is estimated for each region during the histogram fit. Voxels in the intensity-normalized image are then classified into six tissue types using a maximum a posteriori classifier. This classifier combines the partial volume tissue measurement model with a Gibbs prior that models the spatial properties of the brain. We validate each stage of our algorithm on real and phantom data. Using data from the 20 normal MRI brain data sets of the Internet Brain Segmentation Repository, our method achieved average kappa indices of kappa = 0.746 +/- 0.114 for gray matter (GM) and kappa = 0.798 +/- 0.089 for white matter (WM) compared to expert labeled data. Our method achieved average kappa indices kappa = 0.893 +/- 0.041 for GM and kappa = 0.928 +/- 0.039 for WM compared to the ground truth labeling on 12 volumes from the Montreal Neurological Institutes BrainWeb phantom.

Construction of a 3D probabilistic atlas of human cortical structures

We describe the construction of a digital brain atlas composed of data from manually delineated MRI data. A total of 56 structures were labeled in MRI of 40 healthy, normal volunteers. This labeling was performed according to a set of protocols developed for this project. Pairs of raters were assigned to each structure and trained on the protocol for that structure. Each rater pair was tested for concordance on 6 of the 40 brains; once they had achieved reliability standards, they divided the task of delineating the remaining 34 brains. The data were then spatially normalized to well-known templates using 3 popular algorithms: AIR5.2.5s nonlinear warp (Woods et al., 1998) paired with the ICBM452 Warp 5 atlas (Rex et al., 2003), FSLs FLIRT (Smith et al., 2004) was paired with its own template, a skull-stripped version of the ICBM152 T1 average; and SPM5s unified segmentation method (Ashburner and Friston, 2005) was paired with its canonical brain, the whole head ICBM152 T1 average. We thus produced 3 variants of our atlas, where each was constructed from 40 representative samples of a data processing stream that one might use for analysis. For each normalization algorithm, the individual structure delineations were then resampled according to the computed transformations. We next computed averages at each voxel location to estimate the probability of that voxel belonging to each of the 56 structures. Each version of the atlas contains, for every voxel, probability densities for each region, thus providing a resource for automated probabilistic labeling of external data types registered into standard spaces; we also computed average intensity images and tissue density maps based on the three methods and target spaces. These atlases will serve as a resource for diverse applications including meta-analysis of functional and structural imaging data and other bioinformatics applications where display of arbitrary labels in probabilistically defined anatomic space will facilitate both knowledge-based development and visualization of findings from multiple disciplines.

BrainSuite: an automated cortical surface identification tool.

We describe a new magnetic resonance (MR) image analysis tool that produces cortical surface representations with spherical topology from MR images of the human brain. The tool provides a sequence of low-level operations in a single package that can produce accurate brain segmentations in clinical time. The tools include skull and scalp removal, image nonuniformity compensation, voxel-based tissue classification, topological correction, rendering, and editing functions. The collection of tools is designed to require minimal user interaction to produce cortical representations. In this paper we describe the theory of each stage of the cortical surface identification process. We then present classification validation results using real and phantom data. We also present a study of interoperator variability.

Genetics of Brain Fiber Architecture and Intellectual Performance

The study is the first to analyze genetic and environmental factors that affect brain fiber architecture and its genetic linkage with cognitive function. We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4 Tesla), in 92 identical and fraternal twins. White matter integrity, quantified using fractional anisotropy (FA), was used to fit structural equation models (SEM) at each point in the brain, generating three-dimensional maps of heritability. We visualized the anatomical profile of correlations between white matter integrity and full-scale, verbal, and performance intelligence quotients (FIQ, VIQ, and PIQ). White matter integrity (FA) was under strong genetic control and was highly heritable in bilateral frontal (a2 = 0.55, p = 0.04, left; a2 = 0.74, p = 0.006, right), bilateral parietal (a2 = 0.85, p < 0.001, left; a2 = 0.84, p < 0.001, right), and left occipital (a2 = 0.76, p = 0.003) lobes, and was correlated with FIQ and PIQ in the cingulum, optic radiations, superior fronto-occipital fasciculus, internal capsule, callosal isthmus, and the corona radiata (p = 0.04 for FIQ and p = 0.01 for PIQ, corrected for multiple comparisons). In a cross-trait mapping approach, common genetic factors mediated the correlation between IQ and white matter integrity, suggesting a common physiological mechanism for both, and common genetic determination. These genetic brain maps reveal heritable aspects of white matter integrity and should expedite the discovery of single-nucleotide polymorphisms affecting fiber connectivity and cognition.

Visualization of image data from cells to organisms

Advances in imaging techniques and high-throughput technologies are providing scientists with unprecedented possibilities to visualize internal structures of cells, organs and organisms and to collect systematic image data characterizing genes and proteins on a large scale. To make the best use of these increasingly complex and large image data resources, the scientific community must be provided with methods to query, analyze and crosslink these resources to give an intuitive visual representation of the data. This review gives an overview of existing methods and tools for this purpose and highlights some of their limitations and challenges.

Automated graph-based analysis and correction of cortical volume topology

The human cerebral cortex is topologically equivalent to a sheet and can be considered topologically spherical if it is closed at the brainstem. Low-level segmentation of magnetic resonance (MR) imagery typically produces cerebral volumes whose tessellations are not topologically spherical. The authors present a novel algorithm that analyzes and constrains the topology of a volumetric object. Graphs are formed that represent the connectivity of voxel segments in the foreground and background of the image. These graphs are analyzed and minimal corrections to the volume are made prior to tessellation. The authors apply the algorithm to a simple test object and to cerebral white matter masks generated by a low-level tissue identification sequence. The authors tessellate the resulting objects using the marching cubes algorithm and verify their topology by computing their Euler characteristics. A key benefit of the algorithm is that it localizes the change to a volume to the specific areas of its topological defects.

A multimodal, multidimensional atlas of the C57BL/6J mouse brain

Strains of mice, through breeding or the disruption of normal genetic pathways, are widely used to model human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison. We have developed a digital atlas of the adult C57BL/6J mouse brain as a comprehensive framework for storing and accessing the myriad types of information about the mouse brain. Our implementation was constructed using several different imaging techniques: magnetic resonance microscopy, blockface imaging, classical histology and immunohistochemistry. Along with raw and annotated images, it contains database management systems and a set of tools for comparing information from different techniques. The framework allows facile correlation of results from different animals, investigators or laboratories by establishing a canonical representation of the mouse brain and providing the tools for the insertion of independent data into the same space as the atlas. This tool will aid in managing the increasingly complex and voluminous amounts of information about the mammalian brain. It provides a framework that encompasses genetic information in the context of anatomical imaging and holds tremendous promise for producing new insights into the relationship between genotype and phenotype. We describe a suite of tools that enables the independent entry of other types of data, facile retrieval of information and straightforward display of images. Thus, the atlas becomes a framework for managing complex genetic and epigenetic information about the mouse brain. The atlas and associated tools may be accessed at http://www.loni.ucla.edu/MAP.

Qualitative and quantitative evaluation of six algorithms for correcting intensity nonuniformity effects.

The desire to correct intensity nonuniformity in magnetic resonance images has led to the proliferation of nonuniformity-correction (NUC) algorithms with different theoretical underpinnings. In order to provide end users with a rational basis for selecting a given algorithm for a specific neuroscientific application, we evaluated the performance of six NUC algorithms. We used simulated and real MRI data volumes, including six repeat scans of the same subject, in order to rank the accuracy, precision, and stability of the nonuniformity corrections. We also compared algorithms using data volumes from different subjects and different (1.5T and 3.0T) MRI scanners in order to relate differences in algorithmic performance to intersubject variability and/or differences in scanner performance. In phantom studies, the correlation of the extracted with the applied nonuniformity was highest in the transaxial (left-to-right) direction and lowest in the axial (top-to-bottom) direction. Two of the six algorithms demonstrated a high degree of stability, as measured by the iterative application of the algorithm to its corrected output. While none of the algorithms performed ideally under all circumstances, locally adaptive methods generally outperformed nonadaptive methods.

Quantitative Evaluation of Automated Skull-Stripping Methods Applied to Contemporary and Legacy Images: Effects of Diagnosis, Bias Correction, and Slice Location

Performance of automated methods to isolate brain from nonbrain tissues in magnetic resonance (MR) structural images may be influenced by MR signal inhomogeneities, type of MR image set, regional anatomy, and age and diagnosis of subjects studied. The present study compared the performance of four methods: Brain Extraction Tool (BET; Smith [ 2002 ]: Hum Brain Mapp 17:143–155); 3dIntracranial (Ward [ 1999 ] Milwaukee: Biophysics Research Institute, Medical College of Wisconsin; in AFNI); a Hybrid Watershed algorithm (HWA, Segonne et al. [ 2004 ] Neuroimage 22:1060–1075; in FreeSurfer); and Brain Surface Extractor (BSE, Sandor and Leahy [ 1997 ] IEEE Trans Med Imag 16:41–54; Shattuck et al. [ 2001 ] Neuroimage 13:856–876) to manually stripped images. The methods were applied to uncorrected and bias‐corrected datasets; Legacy and Contemporary T1‐weighted image sets; and four diagnostic groups (depressed, Alzheimers, young and elderly control). To provide a criterion for outcome assessment, two experts manually stripped six sagittal sections for each dataset in locations where brain and nonbrain tissue are difficult to distinguish. Methods were compared on Jaccard similarity coefficients, Hausdorff distances, and an Expectation‐Maximization algorithm. Methods tended to perform better on contemporary datasets; bias correction did not significantly improve method performance. Mesial sections were most difficult for all methods. Although AD image sets were most difficult to strip, HWA and BSE were more robust across diagnostic groups compared with 3dIntracranial and BET. With respect to specificity, BSE tended to perform best across all groups, whereas HWA was more sensitive than other methods. The results of this study may direct users towards a method appropriate to their T1‐weighted datasets and improve the efficiency of processing for large, multisite neuroimaging studies. Hum. Brain Mapping, 2005.

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.