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.
Highlights
While water molecules are ubiquitous in the brain, many metabolites detected by magnetic resonance spectroscopy (MRS) in vivo are primarily intracellular, with typical extracellular concentrations ∼1,000–10,000 times lower than intracellular concentrations
We will see how studying the time-dependency of metabolite apparent diffusion coefficient (ADC) allows clarifying the nature of the compartments where MRS-detected metabolites are diffusing, and may allow probing morphological features at different spatial scales
An intracellular diffusion coefficient including some short-range tortuosity along fibers as discussed in the previous paragraph was let as a free parameter in addition to morphometric parameters, and was found to be ∼0.3–0.45 μm2/ms, i.e., lower than those derived from oscillating gradient data, but very close to values derived from high-b values (Kroenke et al, 2004; Ligneul et al, 2017b), suggesting that the latter already include short-range tortuosity
Summary
Received: 25 September 2017 Accepted: 03 January 2018 Published: 19 January 2018. Citation: Valette J, Ligneul C, Marchadour C, Najac C and Palombo M (2018) Brain Metabolite Diffusion from Ultra-Short to Ultra-Long Time Scales: What Do. Their diffusion is expected to purely reflect intracellular properties, opening unique possibilities to use metabolites as specific probes to explore cellular organization and structure. 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.
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