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      White matter microstructural abnormalities in bipolar disorder: A whole brain diffusion tensor imaging study

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          Abstract

          Background

          Bipolar disorder (BD) is a chronic mental illness characterized by severe disruptions in mood and cognition. Diffusion tensor imaging (DTI) studies suggest that white matter (WM) tract abnormalities may contribute to the clinical hallmarks of the disorder. Using DTI and whole brain voxel-based analysis, we mapped the profile of WM anomalies in BD. All patients in our sample were euthymic and lithium free when scanned.

          Methods

          Diffusion-weighted and T1-weighted structural brain images were acquired from 23 lithium-free euthymic subjects with bipolar I disorder and 19 age- and sex-matched healthy control subjects on a 1.5 T MRI scanner. Scans were processed to provide measures of fractional anisotropy (FA) and mean and radial diffusivity (MD and RD) at each WM voxel, and processed scans were nonlinearly aligned to a customized brain imaging template for statistical group comparisons.

          Results

          Relative to controls, the bipolar group showed widespread regions of lower FA, including the corpus callosum, cortical and thalamic association fibers. MD and RD were abnormally elevated in patients in many of these same regions.

          Conclusions

          Our findings agree with prior reports of WM abnormalities in the corpus callosum and further link a bipolar diagnosis with structural abnormalities of the tapetum, fornix and stria terminalis. Future studies assessing the diagnostic specificity and prognostic implications of these abnormalities would be of interest.

          Highlights

          • Using DTI and whole brain voxel-based analysis, we mapped WM anomalies in BD.

          • Relative to controls, the bipolar group showed widespread regions of lower FA.

          • MD and RD were abnormally elevated in patients in many of these same regions.

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          Most cited references90

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          A rating scale for mania: reliability, validity and sensitivity.

          An eleven item clinician-administered Mania Rating Scale (MRS) is introduced, and its reliability, validity and sensitivity are examined. There was a high correlation between the scores of two independent clinicians on both the total score (0.93) and the individual item scores (0.66 to 0.92). The MRS score correlated highly with an independent global rating, and with scores of two other mania rating scales administered concurrently. The score also correlated with the number of days of subsequent stay in hospital. It was able to differentiate statistically patients before and after two weeks of treatment and to distinguish levels of severity based on the global rating.
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            Demyelination increases radial diffusivity in corpus callosum of mouse brain.

            Myelin damage, as seen in multiple sclerosis (MS) and other demyelinating diseases, impairs axonal conduction and can also be associated with axonal degeneration. Accurate assessments of these conditions may be highly beneficial in evaluating and selecting therapeutic strategies for patient management. Recently, an analytical approach examining diffusion tensor imaging (DTI) derived parameters has been proposed to assess the extent of axonal damage, demyelination, or both. The current study uses the well-characterized cuprizone model of experimental demyelination and remyelination of corpus callosum in mouse brain to evaluate the ability of DTI parameters to detect the progression of myelin degeneration and regeneration. Our results demonstrate that the extent of increased radial diffusivity reflects the severity of demyelination in corpus callosum of mouse brain affected by cuprizone treatment. Subsequently, radial diffusivity decreases with the progression of remyelination. Furthermore, radial diffusivity changes were specific to the time course of changes in myelin integrity as distinct from axonal injury, which was detected by betaAPP immunostaining and shown to be most extensive prior to demyelination. Radial diffusivity offers a specific assessment of demyelination and remyelination, as distinct from acute axonal damage.
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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
                Journal
                Neuroimage (Amst)
                Neuroimage (Amst)
                NeuroImage : Clinical
                Elsevier
                2213-1582
                5 April 2013
                5 April 2013
                2013
                : 2
                : 558-568
                Affiliations
                [a ]Imaging Genetics Center, Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA, USA
                [b ]Semel Institute of Neuroscience and Human Behavior, UCLA School of Medicine, Los Angeles, CA, USA
                [c ]Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, CA, USA
                [d ]Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, CA, USA
                Author notes
                [* ]Corresponding author at: Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Neuroscience Research Building 225E, 635 Charles Young Drive, Los Angeles, CA 90095-1769, USA. Tel.: + 1 310 206 2101; fax: + 1 310 206 5518. thompson@ 123456loni.ucla.edu
                Article
                S2213-1582(13)00037-5
                10.1016/j.nicl.2013.03.016
                3777761
                24179807
                53c55d6a-915b-4ce2-87b3-13ed68621e75
                © 2013 The Authors

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

                History
                : 5 February 2013
                : 26 March 2013
                : 27 March 2013
                Categories
                Article

                bipolar disorder,white matter,neuroimaging,dti,brain mapping,fractional anisotropy

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