LactaDiff · Assessing cellular compartmentation of brain lactate using diffusion MR spectroscopy in vivo

The idea has emerged that compartmentation of brain lactate, i.e. its distribution between different cell types and the extracellular space, plays a critical role in neurotransmission and brain plasticity. Dysregulations of lactate metabolism have also been reported in neurodegenerative diseases such as Alzheimer's disease. However, these notions remain challenged, and even fundamental mechanisms such as the astrocyte-to-neuron lactate shuttle, whereby astrocytes are supposed to export lactate to neurons to sustain neuronal energy needs, are still fiercely debated. This is largely due the lack of tools to evaluate cell-specific compartmentation of lactate in the living brain, in particular in Humans.In this project, we will develop new nuclear magnetic resonance spectroscopy techniques to non-invasively measure lactate diffusion, including in cortical regions. We will then take advantage of the unique ability of these methods to differentiate between metabolites diffusing in different environments, based on diffusion properties imposed by the microstructure, to quantify lactate in the extracellular space and, most importantly, in neurons and astrocytes. After validation in rodent models, these methods will be transposed on a clinical MRI system at ultra-high magnetic field, to gain unprecedented access to lactate compartmentation in the Human brain and its modifications during brain activity, plasticity, and in Alzheimer's disease. This will open a new research field for magnetic resonance spectroscopy in vivo.