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

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.