Time-dependent DW-MRS to probe lactate compartmentation in Huntington’s disease mouse model

Motivation: In the healthy brain, lactate compartmentation and exchange are crucial for neurotransmission. In Huntington’s disease (HD), lactate metabolism appears to be impaired, but lactate compartmentation is unkown. Goal(s): To assess lactate compartmentation between intracellular and extracellular spaces under pathological conditions in vivo. Approach: Using time-dependent DW-MRS, which may probe lactate exchange and compartmentation, we measured diffusivity and kurtosis in a cohort of zQ175 mice, a model of HD, versus control mice at 3, 6 and 12 months. Results: Results suggest a larger extracellular fraction in zQ175 mice at 12 months, while no other microstructural changes would be measurable using DW-MRS. Impact: DW-MRS allows probing brain lactate compartmentation, thus unravelling some crucial aspect of lactate metabolism. Results suggest that, while no microstructural alteration can be observed in the zQ175 mouse model of Huntington’s disease, impaired lactate compartmentation is detected with DW-MRS.