@article{discovery10043126,
            note = {{\copyright} 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.},
           month = {January},
          volume = {12},
         journal = {Frontiers in Neuroscience},
            year = {2018},
           title = {Brain Metabolite Diffusion from Ultra-Short to Ultra-Long Time Scales: What Do We Learn, Where Should We Go?},
       publisher = {FRONTIERS MEDIA SA},
          author = {Valette, J and Ligneul, C and Marchadour, C and Najac, C and Palombo, M},
            issn = {1662-453X},
        abstract = {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.},
             url = {http://doi.org/10.3389/fnins.2018.00002},
        keywords = {Science \& Technology, Life Sciences \& Biomedicine, Neurosciences, Neurosciences \& Neurology, intracellular diffusion, brain metabolites, ADC time-dependency, microstructure, diffusion time, MAGNETIC-RESONANCE-SPECTROSCOPY, N-ACETYL-ASPARTATE, WEIGHTED MR SPECTROSCOPY, RAT-BRAIN, IN-VIVO, INTRACELLULAR METABOLITES, H-1-NMR SPECTROSCOPY, ANOMALOUS DIFFUSION, SELF-DIFFUSION, CELL}
}