TY - JOUR ID - discovery10043126 N2 - In vivo diffusion-weighted MR spectroscopy (DW-MRS) allows measuring diffusion properties of brain metabolites. Unlike water, most metabolites are confined within cells. Hence, their diffusion is expected to purely reflect intracellular properties, opening unique possibilities to use metabolites as specific probes to explore cellular organization and structure. However, interpretation and modeling of DW-MRS, and more generally of intracellular diffusion, remains difficult. In this perspective paper, we will focus on the study of the time-dependency of brain metabolite apparent diffusion coefficient (ADC). We will see how measuring ADC over several orders of magnitude of diffusion times, from less than 1 ms to more than 1 s, allows clarifying our understanding of brain metabolite diffusion, by firmly establishing that metabolites are neither massively transported by active mechanisms nor massively confined in subcellular compartments or cell bodies. Metabolites appear to be instead diffusing in long fibers typical of neurons and glial cells such as astrocytes. Furthermore, we will evoke modeling of ADC time-dependency to evaluate the effect of, and possibly quantify, some structural parameters at various spatial scales, departing from a simple model of hollow cylinders and introducing additional complexity, either short-ranged (such as dendritic spines) or long-ranged (such as cellular fibers ramification). Finally, we will discuss the experimental feasibility and expected benefits of extending the range of diffusion times toward even shorter and longer values. SN - 1662-453X UR - http://doi.org/10.3389/fnins.2018.00002 PB - FRONTIERS MEDIA SA JF - Frontiers in Neuroscience KW - Science & Technology KW - Life Sciences & Biomedicine KW - Neurosciences KW - Neurosciences & Neurology KW - intracellular diffusion KW - brain metabolites KW - ADC time-dependency KW - microstructure KW - diffusion time KW - MAGNETIC-RESONANCE-SPECTROSCOPY KW - N-ACETYL-ASPARTATE KW - WEIGHTED MR SPECTROSCOPY KW - RAT-BRAIN KW - IN-VIVO KW - INTRACELLULAR METABOLITES KW - H-1-NMR SPECTROSCOPY KW - ANOMALOUS DIFFUSION KW - SELF-DIFFUSION KW - CELL A1 - Valette, J A1 - Ligneul, C A1 - Marchadour, C A1 - Najac, C A1 - Palombo, M TI - Brain Metabolite Diffusion from Ultra-Short to Ultra-Long Time Scales: What Do We Learn, Where Should We Go? EP - 6 AV - public Y1 - 2018/01/19/ VL - 12 N1 - © 2018 Valette, Ligneul, Marchadour, Najac and Palombo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. ER -