Insights into brain microstructure from in vivo DW-MRS

Abstract

Many developmental processes, such as plasticity and aging, or pathological processes such as neurological diseases are characterized by modulations of specific cellular types and their microstructures. Diffusion-weighted Magnetic Resonance Imaging (DW-MRI) is a powerful technique for probing microstructure, yet its information arises from the ubiquitous, non-specific water signal. By contrast, diffusion-weighted Magnetic Resonance Spectroscopy (DW-MRS) allows specific characterizations of tissues such as brain and muscle in vivo by quantifying the diffusion properties of MR-observable metabolites. Many brain metabolites are predominantly intracellular, and some of them are preferentially localized in specific brain cell populations, e.g., neurons and glia. Given the microstructural sensitivity of diffusion-encoding filters, investigation of metabolite diffusion properties using DW-MRS can thus provide exclusive cell and compartment-specific information. Furthermore, since many models and assumptions are used for quantification of water diffusion, metabolite diffusion may serve to generate a-priori information for model selection in DW-MRI. However, DW-MRS measurements are extremely challenging, from the acquisition to the accurate and correct analysis and quantification stages. In this review, we survey the state-of-the-art methods that have been developed for the robust acquisition, quantification and analysis of DW-MRS data and discuss the potential relevance of DW-MRS for elucidating brain microstructure in vivo. The review highlights that when accurate data on the diffusion of multiple metabolites is combined with accurate computational and geometrical modeling, DW-MRS can provide unique cell-specific information on the intracellular structure of brain tissue, in health and disease, which could serve as incentives for further application in vivo in human research and clinical MRI.

Axon Diameters and Myelin Content Modulate Microscopic Fractional Anisotropy at Short Diffusion Times in Fixed Rat Spinal Cord

“…In fact, the values reported in [44,45]. Further studies are needed to establish which underlying biological components give rise to such high µFA in gray matter, but dendrites, astrocyte branches, and nonmyelinated or myelinated axons traversing gray matter could be suspected [93,99]. Time-dependent or spectroscopic experiments on metabolites could provide insight into such questions in the future.…”

Revisiting double diffusion encoding MRS in the mouse brain at 11.7T: Which microstructural features are we sensitive to?

“…using a pair of diffusion gradients as proposed by Stejskal-Tanner (Stejskal and Tanner, 1965). This is of particular interest because intracellular metabolites are constantly exploring their local environment under the effect of diffusion, thus potentially reporting precious information on several attributes of the cell microstructure such as cell fiber length or diameter (Palombo et al, 2018c). Moreover, unlike water, some metabolites are known to be confined in specific cell compartments, as in the case of NAA and glutamate (Glu), which are neuronal markers, or myo-inositol (Ins) and choline compounds (tCho), which are associated to glial cells (Choi et al, 2007).…”

Diffusion-weighted magnetic resonance spectroscopy enables cell-specific monitoring of astrocyte reactivity in vivo

“…Indeed, most brain metabolites are confined in the intracellular space, and some of them are even considered to be cell-specific: Nacetylaspartate (NAA) and glutamate (Glu) have for example been reported to be mostly found 25 in neurons, while choline compounds (tCho) and myo-inositol (Ins) are thought to be predominantly in glial cells (Choi et al, 2007;Gill et al, 1989) (more particularly in astrocytes for myo-inositol (Brand et al, 1993)). Hence, the diffusion of these metabolites, as measured using diffusion-weighted MRS (DW-MRS), must specifically depend on the cellular structure constraining them (Palombo et al, 2017c). Some recent works, including ours, support this idea:…”

“…2A, macromolecules contribute a lot to high-b spectra: the intensity of the broad macromolecules peak at 0.9 ppm is comparable to NAA intensity. Therefore, it is crucial to properly quantify their signal for such experiments (Palombo et al, 2017c). Here the excellent spectral quality and signal-to-noise ratio SNR at all diffusion-weightings (at b=50 ms/µm 2 the SNR, calculated relative to NAA, is 26 ± 2 in the CNTF group, and 30 ± 2 in the control group), 100 as well as for macromolecules ( Fig.…”

“…indeed, different diffusion behaviors that can be reasonably (and quantitatively) explained in terms of different cellular structure have been reported for neuronal and glial metabolites in the healthy brain (Palombo et al, 2017c). However it has never been established that variations of metabolite diffusion, e.g.…”