title: Myelin and iron concentration in the human brain: a quantitative study of MRI contrast.
abstract: During the last five years ultra-high-field magnetic resonance imaging (MRI) has enabled an unprecedented view of living human brain. Brain tissue contrast in most MRI sequences is known to reflect mainly the spatial distributions of myelin and iron. These distributions have been shown to overlap significantly in many brain regions, especially in the cortex. It is of increasing interest to distinguish and identify cortical areas by their appearance in MRI, which has been shown to be feasible in vivo. Parcellation can benefit greatly from quantification of the independent contributions of iron and myelin to MRI contrast. Recent studies using susceptibility mapping claim to allow such a separation of the effects of myelin and iron in MRI. We show, using post-mortem human brain tissue, that this goal can be achieved. After MRI scanning of the block with appropriate T1 mapping and T2* weighted sequences, we section the block and apply a novel technique, proton induced X-ray emission (PIXE), to spatially map iron, phosphorus and sulfur elemental concentrations, simultaneously with 1μm spatial resolution. Because most brain phosphorus is located in myelin phospholipids, a calibration step utilizing element maps of sulfur enables semi-quantitative ex vivo mapping of myelin concentration. Combining results for iron and myelin concentration in a linear model, we have accurately modeled MRI tissue contrasts. Conversely, iron and myelin concentrations can now be estimated from appropriate MRI measurements in post-mortem brain samples.
authors.affiliation: Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstrasse 1a, 04103 Leipzig, Germany. Electronic address: stueber@cbs.mpg.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Stüber
authors.affiliation: Paul-Flechsig-Institute for Brain Research, Faculty of Medicine, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany; Department of Neuroscience and Physiology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA. Electronic address: Markus.Morawski@medizin.uni-leipzig.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Morawski
authors.affiliation: Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstrasse 1a, 04103 Leipzig, Germany. Electronic address: schaefer@cbs.mpg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäfer
authors.affiliation: Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstrasse 1a, 04103 Leipzig, Germany; Institut Lumière et Matière, UMR5306 Université Claude Bernard Lyon I, F-69622 Villeurbanne, France. Electronic address: labadie@cbs.mpg.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Labadie
authors.affiliation: Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstrasse 1a, 04103 Leipzig, Germany. Electronic address: waehnert@cbs.mpg.de.
authors.forename: Miriam
authors.initials: M
authors.lastname: Wähnert
authors.affiliation: Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstrasse 1a, 04103 Leipzig, Germany. Electronic address: leuze@cbs.mpg.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Leuze
authors.affiliation: Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstrasse 1a, 04103 Leipzig, Germany. Electronic address: streicher@cbs.mpg.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Streicher
authors.affiliation: Institute of Nuclear Solid State Physics, Faculty of Physics, University of Leipzig, Linnéstrasse 5, 04103 Leipzig, Germany. Electronic address: barapatre@physik.uni-leipzig.de.
authors.forename: Nirav
authors.initials: N
authors.lastname: Barapatre
authors.affiliation: Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstrasse 1a, 04103 Leipzig, Germany. Electronic address: reimann@cbs.mpg.de.
authors.forename: Katja
authors.initials: K
authors.lastname: Reimann
authors.affiliation: Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstrasse 1a, 04103 Leipzig, Germany. Electronic address: sgeyer@cbs.mpg.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Geyer
authors.affiliation: Institute of Nuclear Solid State Physics, Faculty of Physics, University of Leipzig, Linnéstrasse 5, 04103 Leipzig, Germany. Electronic address: spemann@uni-leipzig.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Spemann
authors.affiliation: Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstrasse 1a, 04103 Leipzig, Germany. Electronic address: turner@cbs.mpg.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Turner
mesh_terms: D000368:Aged; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D007501:Iron / Q000032:analysis*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009185:Myelin Proteins / Q000032:analysis*
chemical_list: D009185:Myelin Proteins; D007501:Iron
keywords: Magnetic susceptibility; PIXE; Phosphorus; Simulations