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

Abstract

The diffusion of brain intracellular metabolites, as measured using diffusion-weighted magnetic resonance spectroscopy in vivo, is thought to specifically depend on the cellular structure constraining them. However, it has never been established that variations of metabolite diffusion, e.g. as observed in some diseases, could indeed be linked to alterations of cellular morphology. Here we demonstrate, in a mouse model of reactive astrocytes, that advanced diffusion-weighted magnetic resonance spectroscopy acquisition and modeling techniques enable non-invasive detection of reactive astrocyte hypertrophy (increased soma radius, increased fiber radius and length), as inferred from variations of myo-inositol diffusion, and as confirmed by confocal microscopy ex vivo. This establishes that specific alterations of intracellular metabolite diffusion can be measured and related to cell-specific morphological alterations. Furthermore, as reactive astrocytes are a hallmark of many brain pathologies, this work opens exciting perspectives for neuroscience and clinical research.

Mapping microglia and astrocyte activation in vivo using diffusion MRI

“…Diffusion MRI signal has great potential to reveal the inflammatory component in numerous brain conditions ( 27 ), and several efforts have been made to provide microstructural models able to capture features belonging to distinct tissue subcompartments, for example, by including dendrite dispersion ( 28 , 29 ) or a compartment for the soma of neurons ( 30 ). While specificity to glia can be achieved, to some extent, by looking at diffusion of brain metabolites using diffusion-weighted magnetic resonance spectroscopy ( 31 ), to date, no imaging framework is available to specifically look at the cellular signature of glia activation. Here, we propose and validate a strategy to image microglia and astrocyte activation in gray matter using diffusion MRI and demonstrate its translational validity to humans.…”

A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder

“…Therefore, while GABA is the major inhibitory neurotransmitter in the CNS, we are unable to identify whether concentration differences are present in the synapse versus storage vesicles. Future research employing more advanced techniques, specifically diffusion‐weighted MRS [Ligneul et al, ; Ronen, Ercan, & Webb, ], may be able to determine what type of GABA contributes to the measured GABA signal.…”

Studying pre-treatment and ketamine-induced changes in white matter microstructure in the context of ketamine’s antidepressant effects

“…Finally, while preclinical work supports that the dMRI changes observed following ketamine potentially arise due to astrocytic microstructural changes, it is additionally possible that decreases in cell membrane water permeability could contribute to post-treatment increases in FA 29,53 . Future endeavors should aim to differentiate between these two mechanisms by harnessing diffusion-weighted magnetic resonance spectroscopy of myo-inositol 54 and permeability diffusivity imaging 13,55 , methods which provide in vivo measures of astrocyte morphology 54,56 and membrane permeability, respectively.…”