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      Brain iron redistribution in mesial temporal lobe epilepsy: a susceptibility-weighted magnetic resonance imaging study

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          Abstract

          Background

          The roles of iron in epilepsy and its pathophysiological significance are poorly understood, especially whether iron levels are abnormal in subcortcal structures. This study aims to demonstrate whole-brain iron alterations and its clinical relevancies in mesial temporal lobe epilepsy (mTLE) in vivo, using susceptibility-weighted magnetic resonance imaging (SWI).

          Methods

          We studied 62 patients with mTLE and 62 healthy controls. Brain iron concentration was quantified using SWI phase values. Voxel-wise analysis was carried out to compare iron levels between mTLE and controls, and to assess the relationship between altered iron concentration and clinical parameters in mTLE.

          Results

          Patients with mTLE showed decreases of iron levels in the subcortical structures such as substantia nigra, red nucleus, and basal ganglia. Conversely, iron levels were decreased in the cortex. Subcortical iron levels were negatively correlated to those in the cortex. Moreover, cortical and basal ganglia iron levels were related to clinical variables including epilepsy duration, age at seizures onset, and histories of precipitating factors.

          Conclusions

          Our SWI findings suggest a redistribution of iron between subcortical and cortical structures in mTLE. The degree of redistribution is affected by both progression of epilepsy and precipitating factors. Investigation on brain iron redistribution offers new insights into the pathogenesis of mTLE, and may be a potential biomarker for monitoring the clinical progression of epilepsy.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12868-014-0117-3) contains supplementary material, which is available to authorized users.

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          Most cited references28

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Susceptibility weighted imaging (SWI).

            Susceptibility differences between tissues can be utilized as a new type of contrast in MRI that is different from spin density, T1-, or T2-weighted imaging. Signals from substances with different magnetic susceptibilities compared to their neighboring tissue will become out of phase with these tissues at sufficiently long echo times (TEs). Thus, phase imaging offers a means of enhancing contrast in MRI. Specifically, the phase images themselves can provide excellent contrast between gray matter (GM) and white matter (WM), iron-laden tissues, venous blood vessels, and other tissues with susceptibilities that are different from the background tissue. Also, for the first time, projection phase images are shown to demonstrate tissue (vessel) continuity. In this work, the best approach for combining magnitude and phase images is discussed. The phase images are high-pass-filtered and then transformed to a special phase mask that varies in amplitude between zero and unity. This mask is multiplied a few times into the original magnitude image to create enhanced contrast between tissues with different susceptibilities. For this reason, this method is referred to as susceptibility-weighted imaging (SWI). Mathematical arguments are presented to determine the number of phase mask multiplications that should take place. Examples are given for enhancing GM/WM contrast and water/fat contrast, identifying brain iron, and visualizing veins in the brain. Copyright 2004 Wiley-Liss, Inc.
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              Imaging iron stores in the brain using magnetic resonance imaging.

              For the last century, there has been great physiological interest in brain iron and its role in brain function and disease. It is well known that iron accumulates in the brain for people with Huntington's disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis, chronic hemorrhage, cerebral infarction, anemia, thalassemia, hemochromatosis, Hallervorden-Spatz, Down syndrome, AIDS and in the eye for people with macular degeneration. Measuring the amount of nonheme iron in the body may well lead to not only a better understanding of the disease progression but an ability to predict outcome. As there are many forms of iron in the brain, separating them and quantifying each type have been a major challenge. In this review, we present our understanding of attempts to measure brain iron and the potential of doing so with magnetic resonance imaging. Specifically, we examine the response of the magnetic resonance visible iron in tissue that produces signal changes in both magnitude and phase images. These images seem to correlate with brain iron content, perhaps ferritin specifically, but still have not been successfully exploited to accurately and precisely quantify brain iron. For future quantitative studies of iron content we propose four methods: correlating R2' and phase to iron content; applying a special filter to the phase to obtain a susceptibility map; using complex analysis to extract the product of susceptibility and volume content of the susceptibility source; and using early and late echo information to separately predict susceptibility and volume content.
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                Author and article information

                Contributors
                zhangzq2001@126.com
                weiliao.wl@gmail.com
                boris.bernhardt@gmail.com
                fmriwangzg@126.com
                Tanqifu126@126.com
                yangfang021011@163.com
                yijunliu@psychiatry.ufl.edu
                cjr.luguangming@vip.163.com
                Journal
                BMC Neurosci
                BMC Neurosci
                BMC Neuroscience
                BioMed Central (London )
                1471-2202
                21 November 2014
                21 November 2014
                2014
                : 15
                : 1
                : 117
                Affiliations
                [ ]Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, 305# Eastern Zhongshan Rd, Nanjing, 210002 China
                [ ]Center for Cognition and Brain Disorders, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015 China
                [ ]Department of Social Neuroscience, Max Planck Institute for Human Cognitive and Brain Science, Leipzig, Germany
                [ ]Department of Neurosurgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002 China
                [ ]Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002 China
                [ ]Department of Psychiatry and Neuroscience, University of Florida, Gainesville, Fl USA
                Article
                117
                10.1186/s12868-014-0117-3
                4243317
                25413842
                ec35496d-f8b8-4c0b-b93b-4d9e9d916aa4
                © Zhang et al.; licensee BioMed Central Ltd. 2014

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 19 May 2014
                : 7 October 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Neurosciences
                brain iron,mesial temporal lobe epilepsy,susceptibility-weighted magnetic resonance imaging

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