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      Reduced Ventral Cingulum Integrity and Increased Behavioral Problems in Children with Isolated Optic Nerve Hypoplasia and Mild to Moderate or No Visual Impairment

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          Abstract

          Objectives

          To assess the prevalence of behavioral problems in children with isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no developmental delay. To identify white matter abnormalities that may provide neural correlates for any behavioral abnormalities identified.

          Patients and Methods

          Eleven children with isolated optic nerve hypoplasia (mean age 5.9 years) underwent behavioral assessment and brain diffusion tensor imaging, Twenty four controls with isolated short stature (mean age 6.4 years) underwent MRI, 11 of whom also completed behavioral assessments. Fractional anisotropy images were processed using tract-based spatial statistics. Partial correlation between ventral cingulum, corpus callosum and optic radiation fractional anisotropy, and child behavioral checklist scores (controlled for age at scan and sex) was performed.

          Results

          Children with optic nerve hypoplasia had significantly higher scores on the child behavioral checklist (p<0.05) than controls (4 had scores in the clinically significant range). Ventral cingulum, corpus callosum and optic radiation fractional anisotropy were significantly reduced in children with optic nerve hypoplasia. Right ventral cingulum fractional anisotropy correlated with total and externalising child behavioral checklist scores (r = −0.52, p<0.02, r = −0.46, p<0.049 respectively). There were no significant correlations between left ventral cingulum, corpus callosum or optic radiation fractional anisotropy and behavioral scores.

          Conclusions

          Our findings suggest that children with optic nerve hypoplasia and mild to moderate or no visual impairment require behavioral assessment to determine the presence of clinically significant behavioral problems. Reduced structural integrity of the ventral cingulum correlated with behavioral scores, suggesting that these white matter abnormalities may be clinically significant. The presence of reduced fractional anisotropy in the optic radiations of children with mild to moderate or no visual impairment raises questions as to the pathogenesis of these changes which will need to be addressed by future studies.

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          Most cited references18

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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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            Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data.

            There has been much recent interest in using magnetic resonance diffusion imaging to provide information about anatomical connectivity in the brain, by measuring the anisotropic diffusion of water in white matter tracts. One of the measures most commonly derived from diffusion data is fractional anisotropy (FA), which quantifies how strongly directional the local tract structure is. Many imaging studies are starting to use FA images in voxelwise statistical analyses, in order to localise brain changes related to development, degeneration and disease. However, optimal analysis is compromised by the use of standard registration algorithms; there has not to date been a satisfactory solution to the question of how to align FA images from multiple subjects in a way that allows for valid conclusions to be drawn from the subsequent voxelwise analysis. Furthermore, the arbitrariness of the choice of spatial smoothing extent has not yet been resolved. In this paper, we present a new method that aims to solve these issues via (a) carefully tuned non-linear registration, followed by (b) projection onto an alignment-invariant tract representation (the "mean FA skeleton"). We refer to this new approach as Tract-Based Spatial Statistics (TBSS). TBSS aims to improve the sensitivity, objectivity and interpretability of analysis of multi-subject diffusion imaging studies. We describe TBSS in detail and present example TBSS results from several diffusion imaging studies.
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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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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                12 March 2013
                : 8
                : 3
                : e59048
                Affiliations
                [1 ]Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, University College London Institute of Child Health, London, United Kingdom
                [2 ]Neurosciences Unit, UCL Institute of Child Health and Developmental Vision Clinic, Great Ormond Street Children’s Hospital, London, United Kingdom
                [3 ]Imaging and Biophysics Unit, University College London Institute of Child Health, London, United Kingdom
                University of Maryland, College Park, United States of America
                Author notes

                Competing Interests: This study was sponsored by The Child Growth Foundation and an unrestricted educational grant from Novo Nordisk Ltd. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

                Involved in reviewing the manuscript: EAW MO JC KS ND AS CC MTD. Approved the final version of the manuscript: EAW MO JC KS ND AS CC MTD. Conceived and designed the experiments: EAW MO JC ND AS CC MTD. Performed the experiments: EAW MO JC KS. Analyzed the data: EAW MO. Contributed reagents/materials/analysis tools: JC CC. Wrote the paper: EAW.

                ¶ These authors also contributed equally to this work.

                Article
                PONE-D-12-22311
                10.1371/journal.pone.0059048
                3595222
                23554967
                04f303fe-b2d0-476f-a2f4-d63e4b102d69
                Copyright @ 2013

                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
                : 28 July 2012
                : 11 February 2013
                Page count
                Pages: 8
                Funding
                This study was sponsored by The Child Growth Foundation and an unrestricted educational grant from Novo Nordisk Ltd. EAW and MOR are sponsored by The Child Growth Foundation and an unrestricted educational grant from Novo Nordisk Ltd. MTD is funded by Great Ormond Street Children’s Charity. JC, KS, AS, ND and CC have nothing to declare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Endocrinology
                Pediatric Endocrinology
                Neurology
                Developmental and Pediatric Neurology
                Neuroimaging
                Ophthalmology
                Pediatric Ophthalmology
                Radiology
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Social and Behavioral Sciences
                Psychology
                Behavior

                Uncategorized
                Uncategorized

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