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      Characterization of Brain Iron Deposition Pattern and Its Association With Genetic Risk Factor in Alzheimer’s Disease Using Susceptibility-Weighted Imaging

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          Abstract

          The presence of iron is an important factor for normal brain functions, whereas excessive deposition of iron may impair normal cognitive function in the brain and lead to Alzheimer’s disease (AD). MRI has been widely applied to characterize brain structural and functional changes caused by AD. However, the effectiveness of using susceptibility-weighted imaging (SWI) for the analysis of brain iron deposition is still unclear, especially within the context of early AD diagnosis. Thus, in this study, we aim to explore the relationship between brain iron deposition measured by SWI with the progression of AD using various feature selection and classification methods. The proposed model was evaluated on a 69-subject SWI imaging dataset consisting of 24 AD patients, 21 mild cognitive impairment patients, and 24 normal controls. The identified AD progression-related regions were then compared with the regions reported from previous genetic association studies, and we observed considerable overlap between these two. Further, we have identified a new potential AD-related gene (MEF2C) closely related to the interaction between iron deposition and AD progression in the brain.

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          Most cited references56

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          Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease

          Neurology, 34(7), 939-939
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            A fast diffeomorphic image registration algorithm.

            This paper describes DARTEL, which is an algorithm for diffeomorphic image registration. It is implemented for both 2D and 3D image registration and has been formulated to include an option for estimating inverse consistent deformations. Nonlinear registration is considered as a local optimisation problem, which is solved using a Levenberg-Marquardt strategy. The necessary matrix solutions are obtained in reasonable time using a multigrid method. A constant Eulerian velocity framework is used, which allows a rapid scaling and squaring method to be used in the computations. DARTEL has been applied to intersubject registration of 471 whole brain images, and the resulting deformations were evaluated in terms of how well they encode the shape information necessary to separate male and female subjects and to predict the ages of the subjects.
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              BrainNet Viewer: A Network Visualization Tool for Human Brain Connectomics

              The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI), we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/).
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                Author and article information

                Contributors
                Journal
                Front Hum Neurosci
                Front Hum Neurosci
                Front. Hum. Neurosci.
                Frontiers in Human Neuroscience
                Frontiers Media S.A.
                1662-5161
                07 June 2021
                2021
                : 15
                : 654381
                Affiliations
                [1] 1Beijing International Center for Mathematical Research, Peking University , Beijing, China
                [2] 2Massachusetts General Hospital and Harvard Medical School , Boston, MA, United States
                [3] 3Peking University Institute of Mental Health (Sixth Hospital) , Beijing, China
                [4] 4National Clinical Research Center for Mental Disorders and Key Laboratory of Mental Health, Ministry of Health, Peking University , Beijing, China
                [5] 5Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia , Beijing, China
                Author notes

                Edited by: Dajiang Zhu, University of Texas at Arlington, United States

                Reviewed by: Jingwen Yan, Indiana University, United States; Yong Liu, Beijing University of Posts and Telecommunications (BUPT), China

                *Correspondence: Huali Wang, huali_wang@ 123456bjmu.edu.cn

                These authors share first authorship

                This article was submitted to Brain Imaging and Stimulation, a section of the journal Frontiers in Human Neuroscience

                Article
                10.3389/fnhum.2021.654381
                8215439
                34163341
                d697c229-b2df-4f87-9444-3a57396e1e5e
                Copyright © 2021 You, Li, Wang, Wang, Dong and Li.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 January 2021
                : 27 April 2021
                Page count
                Figures: 2, Tables: 3, Equations: 6, References: 56, Pages: 9, Words: 0
                Categories
                Human Neuroscience
                Original Research

                Neurosciences
                alzheimer’s disease,brain iron deposition,swi,feature selection,genetic risk factor

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