Probing alterations of brain microstructure in 3xTg-AD mouse via water and metabolites diffusion time-dependence

Motivation: Diffusion-weighted MR Spectroscopy(DW-MRS) gives access to diffusion properties of endogenous intracellular metabolites to characterize brain cell microstructure&microenvironment, which could potentially reflect changes in neuropathology during early Alzheimer's disease(AD). Goal(s): To measure the time-dependent diffusion and kurtosis of the intracellular metabolites and water in the 3xTg-AD mouse. Approach: In-vivo DW-MRS was applied to measure the hippocampus location at different diffusion-times(Td) in four 3xTg mice and four wild-type-C57BL/6 mice(200-day-old/females). Results: The intracellular metabolites change distinctly compared to water in Td-dependency and restricted diffusion between AD and control group. The Kurtosis of metabolites increased significantly in early-AD while water diffusion showed no difference between 2 groups. Impact: This work provides a unique insight into the diffusion time-dependency and kurtosis measurements of intracellular metabolites and water to probe the microstructural changes during the early presymptomatic stages of AD, which helps revealing some underlying processes during AD pathogenesis.