Characterizing extracellular diffusion properties using diffusion-weighted MRS of sucrose injected in mouse brain

Area of Science:

• Neuroimaging
• Biophysics
• Diffusion MRI

Background:

• Brain water and metabolites like lactate and glucose exist in intracellular (ICS) and extracellular spaces (ECS).
• Interpreting diffusion MRI/MRS data is challenging due to ubiquitous metabolite distribution.
• Exogenous probes are used to assess ECS diffusion properties and tortuosity.

Purpose of the Study:

• To thoroughly characterize ECS diffusion properties using sucrose as an exogenous marker in mice.
• To investigate short-range restriction, time-dependent ADC, and microscopic anisotropy of ECS diffusion.
• To compare sucrose diffusion behavior with intracellular metabolites.

Main Methods:

• Injection of sucrose into mouse lateral ventricles or prefrontal cortex.
• Diffusion MRI acquisition at high b values to assess signal attenuation.
• Measurement of ADC time-dependence at long diffusion times.
• Double diffusion encoding (DDE) measurements for microscopic anisotropy.

Main Results:

• Sucrose diffusion is faster than intracellular metabolites and shows sensitivity to restriction at high b values, indicating non-Gaussian diffusion.
• The apparent diffusion coefficient (ADC) time-dependence suggests the tortuosity regime is not yet reached for sucrose.
• DDE experiments indicate sucrose is not trapped in elongated structures within the ECS.
• No significant differences in sucrose diffusion were observed between injection routes or brain regions.

Conclusions:

• Sucrose diffusion in the ECS exhibits distinct characteristics compared to intracellular metabolites.
• These findings provide crucial insights for interpreting and modeling diffusion signals in compartments with both ICS and ECS components.
• The study advances the understanding of extracellular space diffusion dynamics.