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      Ensemble Tractography

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          Abstract

          Tractography uses diffusion MRI to estimate the trajectory and cortical projection zones of white matter fascicles in the living human brain. There are many different tractography algorithms and each requires the user to set several parameters, such as curvature threshold. Choosing a single algorithm with specific parameters poses two challenges. First, different algorithms and parameter values produce different results. Second, the optimal choice of algorithm and parameter value may differ between different white matter regions or different fascicles, subjects, and acquisition parameters. We propose using ensemble methods to reduce algorithm and parameter dependencies. To do so we separate the processes of fascicle generation and evaluation. Specifically, we analyze the value of creating optimized connectomes by systematically combining candidate streamlines from an ensemble of algorithms (deterministic and probabilistic) and systematically varying parameters (curvature and stopping criterion). The ensemble approach leads to optimized connectomes that provide better cross-validated prediction error of the diffusion MRI data than optimized connectomes generated using a single-algorithm or parameter set. Furthermore, the ensemble approach produces connectomes that contain both short- and long-range fascicles, whereas single-parameter connectomes are biased towards one or the other. In summary, a systematic ensemble tractography approach can produce connectomes that are superior to standard single parameter estimates both for predicting the diffusion measurements and estimating white matter fascicles.

          Author Summary

          Diffusion MRI and tractography opened a new avenue for studying white matter fascicles and their tissue properties in the living human brain. There are many different tractography methods, and each requires the user to set several parameters. A limitation of tractography is that the results depend on the selection of algorithms and parameters. Here, we analyze an ensemble method, Ensemble Tractography (ET), that reduces the effect of algorithm and parameter selection. ET creates a large set of candidate streamlines using an ensemble of algorithms and parameter values and then selects the streamlines with strong support from the data using a global fascicle evaluation method. Compared to single parameter connectomes, ET connectomes predict diffusion MRI signals better and cover a wider range of white matter volume. Importantly, ET connectomes include both short- and long-association fascicles, which are not typically found together in single-parameter connectomes.

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          Most cited references45

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          Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution.

          Diffusion-weighted (DW) MR images contain information about the orientation of brain white matter fibres that potentially can be used to study human brain connectivity in vivo using tractography techniques. Currently, the diffusion tensor model is widely used to extract fibre directions from DW-MRI data, but fails in regions containing multiple fibre orientations. The spherical deconvolution technique has recently been proposed to address this limitation. It provides an estimate of the fibre orientation distribution (FOD) by assuming the DW signal measured from any fibre bundle is adequately described by a single response function. However, the deconvolution is ill-conditioned and susceptible to noise contamination. This tends to introduce artefactual negative regions in the FOD, which are clearly physically impossible. In this study, the introduction of a constraint on such negative regions is proposed to improve the conditioning of the spherical deconvolution. This approach is shown to provide FOD estimates that are robust to noise whilst preserving angular resolution. The approach also permits the use of super-resolution, whereby more FOD parameters are estimated than were actually measured, improving the angular resolution of the results. The method provides much better defined fibre orientation estimates, and allows orientations to be resolved that are separated by smaller angles than previously possible. This should allow tractography algorithms to be designed that are able to track reliably through crossing fibre regions.
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            Anatomically-constrained tractography: improved diffusion MRI streamlines tractography through effective use of anatomical information.

            Diffusion MRI streamlines tractography suffers from a number of inherent limitations, one of which is the accurate determination of when streamlines should be terminated. Use of an accurate streamlines propagation mask from segmentation of an anatomical image confines the streamlines to the volume of the brain white matter, but does not take full advantage of all of the information available from such an image. We present a modular addition to streamlines tractography, which makes more effective use of the information available from anatomical image segmentation, and the known properties of the neuronal axons being reconstructed, to apply biologically realistic priors to the streamlines generated; we refer to this as "Anatomically-Constrained Tractography". Results indicate that some of the known false positives associated with tractography algorithms are prevented, such that the biological accuracy of the reconstructions should be improved, provided that state-of-the-art streamlines tractography methods are used. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Principles of diffusion tensor imaging and its applications to basic neuroscience research.

              The brain contains more than 100 billion neurons that communicate with each other via axons for the formation of complex neural networks. The structural mapping of such networks during health and disease states is essential for understanding brain function. However, our understanding of brain structural connectivity is surprisingly limited, due in part to the lack of noninvasive methodologies to study axonal anatomy. Diffusion tensor imaging (DTI) is a recently developed MRI technique that can measure macroscopic axonal organization in nervous system tissues. In this article, the principles of DTI methodologies are explained, and several applications introduced, including visualization of axonal tracts in myelin and axonal injuries as well as human brain and mouse embryonic development. The strengths and limitations of DTI and key areas for future research and development are also discussed.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Comput Biol
                PLoS Comput. Biol
                plos
                ploscomp
                PLoS Computational Biology
                Public Library of Science (San Francisco, CA USA )
                1553-734X
                1553-7358
                4 February 2016
                February 2016
                : 12
                : 2
                : e1004692
                Affiliations
                [1 ]Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology, and Osaka University, Suita, Japan
                [2 ]The Japan Society for the Promotion of Science, Tokyo, Japan
                [3 ]Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
                [4 ]Department of Psychology, Stanford University, Stanford, California, United States of America
                [5 ]Instituto Argentino de Radioastronomía (IAR)—CCT La Plata—CONICET, Villa Elisa, Buenos Aires, Argentina
                [6 ]Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States of America
                [7 ]Programs in Neuroscience and Cognitive Science, Indiana University Network Science Institute, Indiana University, Bloomington, Indiana, United States of America
                Oxford University, UNITED KINGDOM
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HT BAW FP. Performed the experiments: HT FP. Analyzed the data: HT BW FP. Contributed reagents/materials/analysis tools: CFC FP. Wrote the paper: HT CFC BAW FP.

                Author information
                http://orcid.org/0000-0002-2096-2384
                http://orcid.org/0000-0001-5437-6095
                http://orcid.org/0000-0002-2469-0494
                Article
                PCOMPBIOL-D-15-00168
                10.1371/journal.pcbi.1004692
                4742469
                26845558
                e56ada72-3ab1-4b7a-a7a0-c52f4c8a805f
                © 2016 Takemura et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 3 February 2015
                : 3 December 2015
                Page count
                Figures: 7, Tables: 0, Pages: 22
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000001, National Science Foundation;
                Award ID: BCS-1228397
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: TR000006, TR000163 and TR000162
                Award Recipient :
                Funded by: Indiana University College of Arts and Sciences Startup funds
                Award Recipient :
                This study was supported by NSF BCS-1228397 to BAW, CTSI GLUE grant funds (NIH TR000006, TR000163 and TR000162) to FP and Indiana University College of Arts and Sciences Startup funds to FP. HT was supported by JSPS Postdoctoral Fellowships for Research Abroad and Grant-in-Aid for JSPS Fellows. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Neuroscience
                Brain Mapping
                Brain Morphometry
                Diffusion Tensor Imaging
                Tractography
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Brain Morphometry
                Diffusion Tensor Imaging
                Tractography
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                Imaging Techniques
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                Magnetic Resonance Imaging
                Brain Morphometry
                Diffusion Tensor Imaging
                Tractography
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                Magnetic Resonance Imaging
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                Diffusion Tensor Imaging
                Tractography
                Research and Analysis Methods
                Imaging Techniques
                Neuroimaging
                Brain Morphometry
                Diffusion Tensor Imaging
                Tractography
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                Custom metadata
                To support reproducible research, the algorithm implementation and example data sets are made available at web sites ( http://purl.stanford.edu/qw092zb0881).

                Quantitative & Systems biology
                Quantitative & Systems biology

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