title: Brain intracellular metabolites are freely diffusing along cell fibers in grey and white matter, as measured by diffusion-weighted MR spectroscopy in the human brain at 7 T.
abstract: Due to the specific compartmentation of brain metabolites, diffusion-weighted magnetic resonance spectroscopy opens unique insight into neuronal and astrocytic microstructures. The apparent diffusion coefficient (ADC) of brain metabolites depends on various intracellular parameters including cytosol viscosity and molecular crowding. When diffusion time (t d) is long enough, the size and geometry of the compartment in which the metabolites diffuse strongly influence metabolites ADC. In a previous study, performed in the macaque brain, we measured neuronal and astrocytic metabolites ADC at long t d (from 86 to 1,011 ms) in a large voxel enclosing an equal proportion of white and grey matter. We showed that metabolites apparently diffuse freely along the axis of dendrites, axons and astrocytic processes. To assess potential differences between these two tissue types, here we measured for the first time in the Human brain the t d-dependency of metabolites trace/3 ADC at 7 teslas using a localized diffusion-weighted STEAM sequence, in parietal and occipital voxels, respectively, containing mainly white and grey matter. We show that, in both tissues and over the observed timescale (t d varying from 92 to 712 ms) metabolite ADC reaches a non-zero plateau, suggesting that metabolites are not confined inside subcellular regions such as cell bodies, or inside subcellular compartments such as organelles, but are rather free to diffuse in the whole fiber-like structure of neurons and astrocytes. Beyond the fundamental insights into intracellular compartmentation of metabolites, this work also provides a new framework for interpreting results of neuroimaging techniques based on molecular diffusion, such as diffusion-weighted magnetic resonance spectroscopy and imaging.
authors.affiliation: Commissariat à l'Energie Atomique (CEA), Molecular Imaging Research Center (MIRCen), Institut d'Imagerie Biomédicale (I2BM), BP no. 6, Bâtiment 61, 18 route du panorama, 92265, Fontenay-aux-Roses, France.|Unité de Recherche Associée CEA-CNRS 2210, Centre National de la Recherche Scientifique (CNRS), BP no. 6, 18 route du panorama, 92265, Fontenay-aux-Roses, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Najac
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Francesca
authors.initials: F
authors.lastname: Branzoli
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Itamar
authors.initials: I
authors.lastname: Ronen
authors.affiliation: Commissariat à l'Energie Atomique (CEA), Molecular Imaging Research Center (MIRCen), Institut d'Imagerie Biomédicale (I2BM), BP no. 6, Bâtiment 61, 18 route du panorama, 92265, Fontenay-aux-Roses, France. julien.valette@cea.fr.|Unité de Recherche Associée CEA-CNRS 2210, Centre National de la Recherche Scientifique (CNRS), BP no. 6, 18 route du panorama, 92265, Fontenay-aux-Roses, France. julien.valette@cea.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Valette
mesh_terms: D000328:Adult; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D066128:Gray Matter / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D066127:White Matter / Q000378:metabolism; D055815:Young Adult
keywords: Diffusion; Human brain; Intracellular compartmentation; Magnetic resonance spectroscopy; Metabolites; Microstructure