Capturing alterations of intracellular-extracellular lactate distribution in the brain using diffusion-weighted MR spectroscopy in vivo.
Sophie MalaquinRodrigo LerchundiEloïse MougelJulien ValettePublished in: Proceedings of the National Academy of Sciences of the United States of America (2024)
While the intracellular-extracellular distribution of lactate has been suggested to play a critical role in the healthy and diseased brain, tools are lacking to noninvasively probe lactate in intracellular and extracellular spaces. Here, we show that, by measuring the diffusion of lactate with diffusion-weighted magnetic resonance (MR) spectroscopy in vivo and comparing it to the diffusion of purely intracellular metabolites, noninvasive quantification of extracellular and intracellular lactate fractions becomes possible. More specifically, we detect alterations of lactate diffusion in the APP/PS1 mouse model of Alzheimer's disease. Data modeling allows quantifying decreased extracellular lactate fraction in APP/PS1 mice as compared to controls, which is quantitatively confirmed with implanted enzyme-microelectrodes. The capability of diffusion-weighted MR spectroscopy to quantify extracellular-intracellular lactate fractions opens a window into brain metabolism, including in Alzheimer's disease.
Keyphrases
- diffusion weighted
- contrast enhanced
- magnetic resonance
- magnetic resonance imaging
- reactive oxygen species
- computed tomography
- mouse model
- resting state
- high resolution
- white matter
- functional connectivity
- cognitive decline
- machine learning
- electronic health record
- adipose tissue
- solid state
- deep learning
- artificial intelligence
- data analysis
- big data
- living cells