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      Myelin Water Imaging Demonstrates Lower Brain Myelination in Children and Adolescents With Poor Reading Ability

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          Abstract

          Magnetic resonance imaging (MRI) provides a means to non-invasively investigate the neurological links with dyslexia, a learning disability that affects one’s ability to read. Most previous brain MRI studies of dyslexia and reading skill have used structural or diffusion imaging to reveal regional brain abnormalities. However, volumetric and diffusion MRI lack specificity in their interpretation at the microstructural level. Myelin is a critical neural component for brain function and plasticity, and as such, deficits in myelin may impact reading ability. MRI can estimate myelin using myelin water fraction (MWF) imaging, which is based on evaluation of the proportion of short T2 myelin-associated water from multi-exponential T2 relaxation analysis, but has not yet been applied to the study of reading or dyslexia. In this study, MWF MRI, intelligence, and reading assessments were acquired in 20 participants aged 10–18 years with a wide range of reading ability to investigate the relationship between reading ability and myelination. Group comparisons showed markedly lower MWF by 16–69% in poor readers relative to good readers in the left and right thalamus, as well as the left posterior limb of the internal capsule, left/right anterior limb of the internal capsule, left/right centrum semiovale, and splenium of the corpus callosum. MWF over the entire group also correlated positively with three different reading scores in the bilateral thalamus as well as white matter, including the splenium of the corpus callosum, left posterior limb of the internal capsule, left anterior limb of the internal capsule, and left centrum semiovale. MWF imaging from T2 relaxation suggests that myelination, particularly in the bilateral thalamus, splenium, and left hemisphere white matter, plays a role in reading abilities. Myelin water imaging thus provides a potentially valuable in vivo imaging tool for the study of dyslexia and its remediation.

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          Advances in functional and structural MR image analysis and implementation as FSL.

          The techniques available for the interrogation and analysis of neuroimaging data have a large influence in determining the flexibility, sensitivity, and scope of neuroimaging experiments. The development of such methodologies has allowed investigators to address scientific questions that could not previously be answered and, as such, has become an important research area in its own right. In this paper, we present a review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB). This research has focussed on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data. The majority of the research laid out in this paper has been implemented as freely available software tools within FMRIB's Software Library (FSL).
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            The basis of anisotropic water diffusion in the nervous system - a technical review.

            Anisotropic water diffusion in neural fibres such as nerve, white matter in spinal cord, or white matter in brain forms the basis for the utilization of diffusion tensor imaging (DTI) to track fibre pathways. The fact that water diffusion is sensitive to the underlying tissue microstructure provides a unique method of assessing the orientation and integrity of these neural fibres, which may be useful in assessing a number of neurological disorders. The purpose of this review is to characterize the relationship of nuclear magnetic resonance measurements of water diffusion and its anisotropy (i.e. directional dependence) with the underlying microstructure of neural fibres. The emphasis of the review will be on model neurological systems both in vitro and in vivo. A systematic discussion of the possible sources of anisotropy and their evaluation will be presented followed by an overview of various studies of restricted diffusion and compartmentation as they relate to anisotropy. Pertinent pathological models, developmental studies and theoretical analyses provide further insight into the basis of anisotropic diffusion and its potential utility in the nervous system. Copyright 2002 John Wiley & Sons, Ltd.
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              About "axial" and "radial" diffusivities.

              This article presents the potential problems arising from the use of "axial" and "radial" diffusivities, derived from the eigenvalues of the diffusion tensor, and their interpretation in terms of the underlying biophysical properties, such as myelin and axonal density. Simulated and in vivo data are shown. The simulations demonstrate that a change in "radial" diffusivity can cause a fictitious change in "axial" diffusivity and vice versa in voxels characterized by crossing fibers. The in vivo data compare the direction of the principle eigenvector in four different subjects, two healthy and two affected by multiple sclerosis, and show that the angle, alpha, between the principal eigenvectors of corresponding voxels of registered datasets is greater than 45 degrees in areas of low anisotropy, severe pathology, and partial volume. Also, there are areas of white matter pathology where the "radial" diffusivity is 10% greater than that of the corresponding normal tissue and where the direction of the principal eigenvector is altered by more than 45 degrees compared to the healthy case. This should strongly discourage researchers from interpreting changes of the "axial" and "radial" diffusivities on the basis of the underlying tissue structure, unless accompanied by a thorough investigation of their mathematical and geometrical properties in each dataset studied. (c) 2009 Wiley-Liss, Inc.
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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
                16 October 2020
                2020
                : 14
                : 568395
                Affiliations
                [1] 1Department of Biomedical Engineering, University of Alberta , Edmonton, AB, Canada
                [2] 2Department of Physics and Astronomy, University of British Columbia , Vancouver, BC, Canada
                [3] 3Department of Education and Counseling Psychology, University of British Columbia , Vancouver, BC, Canada
                [4] 4Philips Health Care , Hamburg, Germany
                [5] 5Department of Radiology, University of Calgary , Calgary, AB, Canada
                [6] 6Department of Radiology, University of British Columbia , Vancouver, BC, Canada
                [7] 7Department of Pathology & Laboratory Medicine, University of British Columbia , Vancouver, BC, Canada
                [8] 8International Collaboration on Repair Discoveries (ICORD), University of British Columbia , Vancouver, BC, Canada
                Author notes

                Edited by: Nandita Vijayakumar, Deakin University, Australia

                Reviewed by: Mustapha Bouhrara, National Institute on Aging (NIH), United States; Heidi M. Feldman, Stanford University, United States

                *Correspondence: Christian Beaulieu christian.beaulieu@ 123456ualberta.ca

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

                Article
                10.3389/fnhum.2020.568395
                7596275
                33192398
                f8c2b723-4c35-414a-b7d3-6142b345d7c1
                Copyright © 2020 Beaulieu, Yip, Low, Mädler, Lebel, Siegel, Mackay and Laule.

                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
                : 01 June 2020
                : 31 August 2020
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 117, Pages: 12, Words: 9893
                Funding
                Funded by: Networks of Centres of Excellence of Canada 10.13039/501100000161
                Funded by: Natural Sciences and Engineering Research Council of Canada 10.13039/501100000038
                Funded by: Canada Research Chairs 10.13039/501100001804
                Funded by: Multiple Sclerosis Society of Canada 10.13039/501100000261
                Categories
                Human Neuroscience
                Original Research

                Neurosciences
                dyslexia,myelin water,mri,reading ability,children,adolescent
                Neurosciences
                dyslexia, myelin water, mri, reading ability, children, adolescent

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