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      D-BRAIN: Anatomically Accurate Simulated Diffusion MRI Brain Data

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          Abstract

          Diffusion Weighted (DW) MRI allows for the non-invasive study of water diffusion inside living tissues. As such, it is useful for the investigation of human brain white matter (WM) connectivity in vivo through fiber tractography (FT) algorithms. Many DW-MRI tailored restoration techniques and FT algorithms have been developed. However, it is not clear how accurately these methods reproduce the WM bundle characteristics in real-world conditions, such as in the presence of noise, partial volume effect, and a limited spatial and angular resolution. The difficulty lies in the lack of a realistic brain phantom on the one hand, and a sufficiently accurate way of modeling the acquisition-related degradation on the other. This paper proposes a software phantom that approximates a human brain to a high degree of realism and that can incorporate complex brain-like structural features. We refer to it as a Diffusion BRAIN (D-BRAIN) phantom. Also, we propose an accurate model of a (DW) MRI acquisition protocol to allow for validation of methods in realistic conditions with data imperfections. The phantom model simulates anatomical and diffusion properties for multiple brain tissue components, and can serve as a ground-truth to evaluate FT algorithms, among others. The simulation of the acquisition process allows one to include noise, partial volume effects, and limited spatial and angular resolution in the images. In this way, the effect of image artifacts on, for instance, fiber tractography can be investigated with great detail. The proposed framework enables reliable and quantitative evaluation of DW-MR image processing and FT algorithms at the level of large-scale WM structures. The effect of noise levels and other data characteristics on cortico-cortical connectivity and tractography-based grey matter parcellation can be investigated as well.

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          Rich-club organization of the human connectome.

          The human brain is a complex network of interlinked regions. Recent studies have demonstrated the existence of a number of highly connected and highly central neocortical hub regions, regions that play a key role in global information integration between different parts of the network. The potential functional importance of these "brain hubs" is underscored by recent studies showing that disturbances of their structural and functional connectivity profile are linked to neuropathology. This study aims to map out both the subcortical and neocortical hubs of the brain and examine their mutual relationship, particularly their structural linkages. Here, we demonstrate that brain hubs form a so-called "rich club," characterized by a tendency for high-degree nodes to be more densely connected among themselves than nodes of a lower degree, providing important information on the higher-level topology of the brain network. Whole-brain structural networks of 21 subjects were reconstructed using diffusion tensor imaging data. Examining the connectivity profile of these networks revealed a group of 12 strongly interconnected bihemispheric hub regions, comprising the precuneus, superior frontal and superior parietal cortex, as well as the subcortical hippocampus, putamen, and thalamus. Importantly, these hub regions were found to be more densely interconnected than would be expected based solely on their degree, together forming a rich club. We discuss the potential functional implications of the rich-club organization of the human connectome, particularly in light of its role in information integration and in conferring robustness to its structural core.
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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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              Diffusion tensor tractography reveals abnormal topological organization in structural cortical networks in Alzheimer's disease.

              Recent research on Alzheimer's disease (AD) has shown that the decline of cognitive and memory functions is accompanied by a disrupted neuronal connectivity characterized by white matter (WM) degeneration. However, changes in the topological organization of WM structural network in AD remain largely unknown. Here, we used diffusion tensor image tractography to construct the human brain WM networks of 25 AD patients and 30 age- and sex-matched healthy controls, followed by a graph theoretical analysis. We found that both AD patients and controls had a small-world topology in WM network, suggesting an optimal balance between structurally segregated and integrative organization. More important, the AD patients exhibited increased shortest path length and decreased global efficiency in WM network compared with controls, implying abnormal topological organization. Furthermore, we showed that the WM network contained highly connected hub regions that were predominately located in the precuneus, cingulate cortex, and dorsolateral prefrontal cortex, which was consistent with the previous diffusion-MRI studies. Specifically, AD patients were found to have reduced nodal efficiency predominantly located in the frontal regions. Finally, we showed that the alterations of various network properties were significantly correlated with the behavior performances. Together, the present study demonstrated for the first time that the Alzheimer's brain was associated with disrupted topological organization in the large-scale WM structural networks, thus providing the structural evidence for abnormalities of systematic integrity in this disease. This work could also have implications for understanding how the abnormalities of structural connectivity in AD underlie behavioral deficits in the patients.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2016
                1 March 2016
                : 11
                : 3
                : e0149778
                Affiliations
                [1 ]iMinds - IPI - TELIN, Ghent University, Ghent, Belgium
                [2 ]iMinds - Vision Lab, Department of Physics, University of Antwerp, Antwerp, Belgium
                [3 ]Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands
                University of Minnesota, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: DP BJ JA JS AP AL WP. Performed the experiments: DP. Analyzed the data: DP JA AL. Contributed reagents/materials/analysis tools: DP BJ TR JS AP AL WP. Wrote the paper: DP BJ JA TR JS AP AL WP.

                Article
                PONE-D-14-56811
                10.1371/journal.pone.0149778
                4773122
                26930054
                3bc1fa6c-4fa3-4f69-8f29-b116bcc16810
                © 2016 Perrone 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
                : 8 January 2015
                : 4 February 2016
                Page count
                Figures: 10, Tables: 1, Pages: 23
                Funding
                This work was supported by the Fund for Scientific Research-Flanders (FWO). The authors thank the Interuniversity Attraction Poles Program (P7/11) initiated by the Belgian Science Policy Office. Ben Jeurissen is a postdoctoral fellow of the Research Fund Flanders (FWO). The research of A.L. is supported by VIDI Grant 639.072.411 from the Netherlands Organisation for Scientific Research (NWO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                All relevant data are available via Figshare ( https://dx.doi.org/10.6084/m9.figshare.2199001.v3).

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