UNC-Utah NA-MIC framework for DTI fiber tract analysis.

Diffusion tensor imaging has become an important modality in the field of neuroimaging to capture changes in micro-organization and to assess white matter integrity or development. While there exists a number of tractography toolsets, these usually lack tools for preprocessing or to analyze diffusion properties along the fiber tracts. Currently, the field is in critical need of a coherent end-to-end toolset for performing an along-fiber tract analysis, accessible to non-technical neuroimaging researchers. The UNC-Utah NA-MIC DTI framework represents a coherent, open source, end-to-end toolset for atlas fiber tract based DTI analysis encompassing DICOM data conversion, quality control, atlas building, fiber tractography, fiber parameterization, and statistical analysis of diffusion properties. Most steps utilize graphical user interfaces (GUI) to simplify interaction and provide an extensive DTI analysis framework for non-technical researchers/investigators. We illustrate the use of our framework on a small sample, cross sectional neuroimaging study of eight healthy 1-year-old children from the Infant Brain Imaging Study (IBIS) Network. In this limited test study, we illustrate the power of our method by quantifying the diffusion properties at 1 year of age on the genu and splenium fiber tracts.

Incorporating population-level variability in orthopedic biomechanical analysis: a review.

Effectively addressing population-level variability within orthopedic analyses requires robust data sets that span the target population and can be greatly facilitated by statistical methods for incorporating such data into functional biomechanical models. Data sets continue to be disseminated that include not just anatomical information but also key mechanical data including tissue or joint stiffness, gait patterns, and other inputs relevant to analysis of joint function across a range of anatomies and physiologies. Statistical modeling can be used to establish correlations between a variety of structural and functional biometrics rooted in these data and to quantify how these correlations change from health to disease and, finally, to joint reconstruction or other clinical intervention. Principal component analysis provides a basis for effectively and efficiently integrating variability in anatomy, tissue properties, joint kinetics, and kinematics into mechanistic models of joint function. With such models, bioengineers are able to study the effects of variability on biomechanical performance, not just on a patient-specific basis but in a way that may be predictive of a larger patient population. The goal of this paper is to demonstrate the broad use of statistical modeling within orthopedics and to discuss ways to continue to leverage these techniques to improve biomechanical understanding of orthopedic systems across populations.

UNC-Utah NA-MIC DTI framework: Atlas Based Fiber Tract Analysis with Application to a Study of Nicotine Smoking Addiction.

PURPOSE: The UNC-Utah NA-MIC DTI framework represents a coherent, open source, atlas fiber tract based DTI analysis framework that addresses the lack of a standardized fiber tract based DTI analysis workflow in the field. Most steps utilize graphical user interfaces (GUI) to simplify interaction and provide an extensive DTI analysis framework for non-technical researchers/investigators. DATA: We illustrate the use of our framework on a 54 directional DWI neuroimaging study contrasting 15 Smokers and 14 Controls. METHODS: At the heart of the framework is a set of tools anchored around the multi-purpose image analysis platform 3D-Slicer. Several workflow steps are handled via external modules called from Slicer in order to provide an integrated approach. Our workflow starts with conversion from DICOM, followed by thorough automatic and interactive quality control (QC), which is a must for a good DTI study. Our framework is centered around a DTI atlas that is either provided as a template or computed directly as an unbiased average atlas from the study data via deformable atlas building. Fiber tracts are defined via interactive tractography and clustering on that atlas. DTI fiber profiles are extracted automatically using the atlas mapping information. These tract parameter profiles are then analyzed using our statistics toolbox (FADTTS). The statistical results are then mapped back on to the fiber bundles and visualized with 3D Slicer. RESULTS: This framework provides a coherent set of tools for DTI quality control and analysis. CONCLUSIONS: This framework will provide the field with a uniform process for DTI quality control and analysis.

Measures for Validation of DTI Tractography.

The evaluation of analysis methods for diffusion tensor imaging (DTI) remains challenging due to the lack of gold standards and validation frameworks. Significant work remains in developing metrics for comparing fiber bundles generated from streamline tractography. We propose a set of volumetric and tract oriented measures for evaluating tract differences. The different methods developed for this assessment work are: an overlap measurement, a point cloud distance and a quantification of the diffusion properties at similar locations between fiber bundles. The application of the measures in this paper is a comparison of atlas generated tractography to tractography generated in individual images. For the validation we used a database of 37 subject DTIs, and applied the measurements on five specific fiber bundles: uncinate, cingulum (left and right for both bundles) and genu. Each measurments is interesting for specific use: the overlap measure presents a simple and comprehensive metric but is sensitive to partial voluming and does not give consistent values depending on the bundle geometry. The point cloud distance associated with a quantile interpretation of the distribution gives a good intuition of how close and similar the bundles are. Finally, the functional difference is useful for a comparison of the diffusion properties since it is the focus of many DTI analysis to compare scalar invariants. The comparison demonstrated reasonable similarity of results. The tract difference measures are also applicable to comparison of tractography algorithms, quality control, reproducibility studies, and other validation problems.

Evaluation of DTI Property Maps as Basis of DTI Atlas Building.

Compared to region of interest based DTI analysis, voxel-based analysis gives higher degree of localization and avoids the procedure of manual delineation with the resulting intra and inter-rater variability. One of the major challenges in voxel-wise DTI analysis is to get high quality voxel-level correspondence. For that purpose, current DTI analysis tools are building on nonlinear registration algorithms that deform individual datasets into a template image that is either precomputed or computed as part of the analysis. A variety of matching criteria and deformation schemes have been proposed, but often comparative evaluation is missing. In our opinion, the use of consistent and unbiased measures to evaluate current DTI procedures is of great importance and our work presents two possible measures. Specifically, we propose the evaluation criteria generalization and specificity, originally introduced by the shape modeling community, to evaluate and compare different DTI nonlinear warping results. These measures are of indirect nature and have a population wise view. Both measures incorporate information of the variability of the registration results in the template space via a voxel-wise PCA model. Thus far, we have used these measures to evaluate our own DTI analysis procedure employing fluid-based registration on scalar DTI maps. Generalization and specificity from tensor images in the template space were computed for 8 scalar property maps. We found that for our procedure an intensity-normalized FA feature outperformed the other scalar measurements. Also, using the tensor images rather than the FA maps as a comparison frame seemed to produce more robust results.

Constrained data decomposition and regression for analyzing healthy aging from fiber tract diffusion properties.

It has been shown that brain structures in normal aging undergo significant changes attributed to neurodevelopmental and neurodegeneration processes as a lifelong, dynamic process. Modeling changes in healthy aging will be necessary to explain differences to neurodegenerative patterns observed in mental illness and neurological disease. Driving application is the analysis of brain white matter properties as a function of age, given a database of diffusion tensor images (DTI) of 86 subjects well-balanced across adulthood. We present a methodology based on constrained PCA (CPCA) for fitting age-related changes of white matter diffusion of fiber tracts. It is shown that CPCA applied to tract functions of diffusion isolates population noise and retains age as a smooth change over time, well represented by the first principal mode. CPCA is therefore applied to a functional data analysis (FDA) problem. Age regression on tract functions reveals a nonlinear trajectory but also age-related changes varying locally along tracts. Four tracts with four different tensor-derived scalar diffusion measures were analyzed, and leave-one-out validation of data compression is shown.

VOXEL-WISE GROUP ANALYSIS OF DTI.

Diffusion tensor MRI (DTI) is now a widely used modality to investigate the fiber tissues in vivo, especially the white matter in brain. An automatic pipeline is described in this paper to conduct a localized voxel-wise multiple-subject group comparison study of DTI. The pipeline consists of 3 steps: 1) Preprocessing, including image format converting, image quality check, eddy-current and motion artifact correction, skull stripping and tensor image estimation, 2) study-specific unbiased DTI atlas computation via affine followed by fluid nonlinear registration and warping of all individual DTI images into the common atlas space to achieve voxel-wise correspondence, 3) voxelwise statistical analysis via heterogeneous linear regression and wild bootstrap technique for correcting for multiple comparisons. This pipeline was applied to process data from a fitness and aging study and preliminary results are presented. The results show that this fully automatic pipeline is suitable for voxel-wise group DTI analysis.

Probabilistic white matter fiber tracking using particle filtering and von Mises-Fisher sampling.

Standard particle filtering technique have previously been applied to the problem of fiber tracking by Brun et al. [Brun, A., Bjornemo, M., Kikinis, R., Westin, C.F., 2002. White matter tractography using sequential importance sampling. In: Proceedings of the ISMRM Annual Meeting, p. 1131] and Bjornemo et al. [Bjornemo, M., Brun, A., Kikinis, R., Westin, C.F., 2002. Regularized stochastic white matter tractography using diffusion tensor MRI, In: Proc. MICCAI, pp. 435-442]. However, these previous attempts have not utilised the full power of the technique, and as a result the fiber paths were tracked in a goal directed way. In this paper, we provide an advanced technique by presenting a fast and novel probabilistic method for white matter fiber tracking in diffusion weighted MRI (DWI), which takes advantage of the weighting and resampling mechanism of particle filtering. We formulate fiber tracking using a non-linear state space model which captures both smoothness regularity of the fibers and the uncertainties in the local fiber orientations due to noise and partial volume effects. Global fiber tracking is then posed as a problem of particle filtering. To model the posterior distribution, we classify voxels of the white matter as either prolate or oblate tensors. We then construct the orientation distributions for prolate and oblate tensors separately. Finally, the importance density function for particle filtering is modeled using the von Mises-Fisher distribution on a unit sphere. Fast and efficient sampling is achieved using Ulrich-Wood's simulation algorithm. Given a seed point, the method is able to rapidly locate the globally optimal fiber and also provides a probability map for potential connections. The proposed method is validated and compared to alternative methods both on synthetic data and real-world brain MRI datasets.

Group analysis of DTI fiber tract statistics with application to neurodevelopment.

Diffusion tensor imaging (DTI) provides a unique source of information about the underlying tissue structure of brain white matter in vivo including both the geometry of major fiber bundles as well as quantitative information about tissue properties represented by derived tensor measures. This paper presents a method for statistical comparison of fiber bundle diffusion properties between populations of diffusion tensor images. Unbiased diffeomorphic atlas building is used to compute a normalized coordinate system for populations of diffusion images. The diffeomorphic transformations between each subject and the atlas provide spatial normalization for the comparison of tract statistics. Diffusion properties, such as fractional anisotropy (FA) and tensor norm, along fiber tracts are modeled as multivariate functions of arc length. Hypothesis testing is performed non-parametrically using permutation testing based on the Hotelling T(2) statistic. The linear discriminant embedded in the T(2) metric provides an intuitive, localized interpretation of detected differences. The proposed methodology was tested on two clinical studies of neurodevelopment. In a study of 1 and 2 year old subjects, a significant increase in FA and a correlated decrease in Frobenius norm was found in several tracts. Significant differences in neonates were found in the splenium tract between controls and subjects with isolated mild ventriculomegaly (MVM) demonstrating the potential of this method for clinical studies.

Group statistics of DTI fiber bundles using spatial functions of tensor measures.

We present a framework for hypothesis testing of differences between groups of DTI fiber tracts. An anatomical, tract-oriented coordinate system provides a basis for estimating the distribution of diffusion properties. The parametrization of sampled, smooth functions is normalized across a population using DTI atlas building. Functional data analysis, an extension of multivariate statistics to continuous functions is applied to the problem of hypothesis testing and discrimination. B-spline models of fractional anisotropy (FA) and Frobenius norm measures are analyzed jointly. Plots of the discrimination direction provide a clinical interpretation of the group differences. The methodology is tested on a pediatric study of subjects aged one and two years.

Quantification of measurement error in DTI: theoretical predictions and validation.

The presence of Rician noise in magnetic resonance imaging (MRI) introduces systematic errors in diffusion tensor imaging (DTI) measurements. This paper evaluates gradient direction schemes and tensor estimation routines to determine how to achieve the maximum accuracy and precision of tensor derived measures for a fixed amount of scan time. We present Monte Carlo simulations that quantify the effect of noise on diffusion measurements and validate these simulation results against appropriate in-vivo images. The predicted values of the systematic and random error caused by imaging noise are essential both for interpreting the results of statistical analysis and for selecting optimal imaging protocols given scan time limitations.

Probabilistic fiber tracking using particle filtering.

This paper presents a novel and fast probabilistic method for white matter fiber tracking from diffusion weighted MRI (DWI). We formulate fiber tracking on a nonlinear state space model which is able to capture both smoothness regularity of fibers and uncertainties of the local fiber orientations due to noise and partial volume effects. The global tracking model is implemented using particle filtering, which allows us to recursively compute the posterior distribution of the potential fibers. The fiber orientation distribution is theoretically formulated for prolate and oblate tensors separately. Fast and efficient sampling is realised using the von Mises-Fisher distribution on unit spheres. Given a seed point, the method is able to rapidly locate the global optimal fiber and also provide a connectivity map. The proposed method is demonstrated on a brain dataset.

Improved correspondence for DTI population studies via unbiased atlas building.

We present a method for automatically finding correspondence in Diffusion Tensor Imaging (DTI) from deformable registration to a common atlas. The registration jointly produces an average DTI atlas, which is unbiased with respect to the choice of a template image, along with diffeomorphic correspondence between each image. The registration image match metric uses a feature detector for thin fiber structures of white matter, and interpolation and averaging of diffusion tensors use the Riemannian symmetric space framework. The anatomically significant correspondence provides a basis for comparison of tensor features and fiber tract geometry in clinical studies and for building DTI population atlases.