title: New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo.
abstract: The brain is one of the most complex organs, and tools are lacking to assess its cellular morphology in vivo. Here we combine original diffusion-weighted magnetic resonance (MR) spectroscopy acquisition and novel modeling strategies to explore the possibility of quantifying brain cell morphology noninvasively. First, the diffusion of cell-specific metabolites is measured at ultra-long diffusion times in the rodent and primate brain in vivo to observe how cell long-range morphology constrains metabolite diffusion. Massive simulations of particles diffusing in synthetic cells parameterized by morphometric statistics are then iterated to fit experimental data. This method yields synthetic cells (tentatively neurons and astrocytes) that exhibit striking qualitative and quantitative similarities with histology (e.g., using Sholl analysis). With our approach, we measure major interspecies difference regarding astrocytes, whereas dendritic organization appears better conserved throughout species. This work suggests that the time dependence of metabolite diffusion coefficient allows distinguishing and quantitatively characterizing brain cell morphologies noninvasively.
authors.affiliation: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Recherche (UMR) 9199 (Neurodegenerative Diseases Laboratory), Université Paris-Sud, Université Paris-Saclay, CNRS, F-92260 Fontenay-aux-Roses, France; marco.palombo@cea.fr julien.valette@cea.fr.
authors.forename: Marco
authors.initials: M
authors.lastname: Palombo
authors.affiliation: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Recherche (UMR) 9199 (Neurodegenerative Diseases Laboratory), Université Paris-Sud, Université Paris-Saclay, CNRS, F-92260 Fontenay-aux-Roses, France;
authors.forename: Clémence
authors.initials: C
authors.lastname: Ligneul
authors.affiliation: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Recherche (UMR) 9199 (Neurodegenerative Diseases Laboratory), Université Paris-Sud, Université Paris-Saclay, CNRS, F-92260 Fontenay-aux-Roses, France;
authors.forename: Chloé
authors.initials: C
authors.lastname: Najac
authors.affiliation: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Recherche (UMR) 9199 (Neurodegenerative Diseases Laboratory), Université Paris-Sud, Université Paris-Saclay, CNRS, F-92260 Fontenay-aux-Roses, France;
authors.forename: Juliette
authors.initials: J
authors.lastname: Le Douce
authors.affiliation: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Service (UMS) 27, INSERM, F-92260 Fontenay-aux-Roses, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Flament
authors.affiliation: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Recherche (UMR) 9199 (Neurodegenerative Diseases Laboratory), Université Paris-Sud, Université Paris-Saclay, CNRS, F-92260 Fontenay-aux-Roses, France;
authors.forename: Carole
authors.initials: C
authors.lastname: Escartin
authors.affiliation: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Recherche (UMR) 9199 (Neurodegenerative Diseases Laboratory), Université Paris-Sud, Université Paris-Saclay, CNRS, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Service (UMS) 27, INSERM, F-92260 Fontenay-aux-Roses, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hantraye
authors.affiliation: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Recherche (UMR) 9199 (Neurodegenerative Diseases Laboratory), Université Paris-Sud, Université Paris-Saclay, CNRS, F-92260 Fontenay-aux-Roses, France;
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Brouillet
authors.affiliation: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Recherche (UMR) 9199 (Neurodegenerative Diseases Laboratory), Université Paris-Sud, Université Paris-Saclay, CNRS, F-92260 Fontenay-aux-Roses, France;
authors.forename: Gilles
authors.initials: G
authors.lastname: Bonvento
authors.affiliation: MIRCen, Institut d'Imagerie Biomédicale, Direction de la Recherche Fondamentale, Commissariat à l'Energie Atomique et aux Energies Alternatives, F-92260 Fontenay-aux-Roses, France; Unité Mixte de Recherche (UMR) 9199 (Neurodegenerative Diseases Laboratory), Université Paris-Sud, Université Paris-Saclay, CNRS, F-92260 Fontenay-aux-Roses, France; marco.palombo@cea.fr julien.valette@cea.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Valette
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001921:Brain / Q000166:cytology / Q000000981:diagnostic imaging; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology*
keywords: cell morphology; diffusion-weighted NMR spectroscopy; metabolites; noninvasive histology; numerical simulations