Assessing Cellular Microstructure in Biological Tissues using In Vivo Diffusion-Weighted Magnetic Resonance.

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Background

Magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques have opened new doors for examining biological tissues in vivo. By combining sensitization to diffusion using magnetic field gradients with a variety of imaging and localization schemes, diffusion-weighted (DW)-MRI and -MRS allow investigating translational diffusion of endogenous molecules, such as water or metabolites, in biological tissues, most commonly the brain but also other organs such as skeletal muscle.

The typical voxel resolution of MRI or MRS is in the millimeter to centimeter range, much lower than the physiologically relevant size of tissue structures, i.e. the cellular scale. However, as molecules are typically diffusing over just a few µm during the duration of the measurement (the “diffusion time”) and encounter numerous biological membranes at these scales, the average cellular microstructure has a critical influence on the measured diffusion signal. Hence, DW-MRI and DW-MRS are sensitive to tissue microstructure at a scale well below the nominal imaging resolution. However, the connection between diffusion properties and tissue microstructure remains indirect, so any attempt to quantify microstructure will require some degree of modeling and validation.

The microstructural features that can be probed and modeled will depend on the molecular probes considered. Water molecules, as detected by DW-MRI, are ubiquitous in living tissues (i.e. they are present in all cells, as well as in the extracellular space), and also can cross biological membranes to some extent. Hence water diffusion is potentially sensitive to microstructure in all compartments including exchange between compartments. Disentangling these parameters, however, may prove very challenging, although the sensitivity to specific parameters may be improved by tuning acquisition parameters such as the diffusion time. In contrast, most metabolites detected by DW-MRS are specifically intracellular, and some of them are even thought to be specific to certain types of cells such as neurons or glial cells in the brain, allowing a more direct access to the intracellular space, and arguably simpler modeling. However, this comes at the expense of much decreased signal-to-noise ratio, as metabolites are typically concentrated 10^4 less than water, hence requiring correspondingly increased detection volume.

The goal of this Research Topic is to gather experts in various acquisition and modeling strategies and show how these approaches, despite their own strengths and weakness, can yield unique information about cellular microstructure, and sometimes complement each other.

Keywords: Magnetic resonance, MRI, diffusion, microstructure

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