The interaction between apparent diffusion coefficients and transverse relaxation rates of human brain metabolites and water studied by diffusion-weighted spectroscopy at 7 T.

The dependence of apparent diffusion coefficients (ADCs) of molecules in biological tissues on an acquisition-specific timescale is a powerful mechanism for studying tissue microstructure. Unlike water, metabolites are confined mainly to intracellular compartments, thus providing higher specificity to tissue microstructure. Compartment-specific structural and chemical properties may also affect molecule transverse relaxation times (T₂). Here, we investigated the correlation between diffusion and relaxation for N-acetylaspartate, creatine and choline compounds in human brain white matter in vivo at 7 T, and compared them with those of water under the same experimental conditions. Data were acquired in a volume of interest in parietal white matter at two different diffusion times, Δ = 44 and 246 ms, using a matrix of three echo times (T(E)) and five diffusion weighting values (up to 4575 s/mm²). Significant differences in the dependence of the ADCs on T(E) were found between water and metabolites, as well as among the different metabolites. A significant decrease in water ADC as a function of TE was observed only at the longest diffusion time (p < 0.001), supporting the hypothesis that at least part of the restricted water pool can be associated with longer T₂, as suggested by previous studies in vitro. Metabolite data showed an increase of creatine (p < 0.05) and N-acetylaspartate (p < 0.05) ADCs with TE at Δ = 44 ms, and a decrease of creatine (p < 0.05) and N-acetylaspartate (p = 0.1) ADCs with TE at Δ = 246 ms. No dependence of choline ADC on TE was observed. The metabolite results suggest that diffusion and relaxation properties are dictated not only by metabolite distribution in different cell types, but also by other mechanisms, such as interactions with membranes, exchange between "free" and "bound" states or interactions with microsusceptibility gradients.