Evidence for biexponential glutamate T₂ relaxation in human visual cortex at 3T: A functional MRS study

Functional magnetic resonance spectroscopy (fMRS) measures dynamic changes in metabolite concentration in response to neural stimulation. The biophysical basis of these changes remains unclear. One hypothesis suggests that an increase or decrease in the glutamate signal detected by fMRS could be due to neurotransmitter movements between cellular compartments with different T₂ relaxation times. Previous studies reporting glutamate (Glu) T₂ values have generally sampled at echo times (TEs) within the range of 30-450 ms, which is not adequate to observe a component with short T₂ (<20 ms). Here, we acquire MRS measurements for Glu, (t) total creatine (tCr) and total N-acetylaspartate (tNAA) from the visual cortex in 14 healthy participants at a range of TE values between 9.3-280 ms during short blocks (64 s) of flickering checkerboards and rest to examine both the short- and long-T₂ components of the curve. We fit monoexponential and biexponential Glu, tCr and tNAA T₂ relaxation curves for rest and stimulation and use Akaike information criterion to assess best model fit. We also include power calculations for detection of a 2% shift of Glu between compartments for each TE. Using pooled data over all participants at rest, we observed a short Glu T₂-component with T₂ = 10 ms and volume fraction of 0.35, a short tCr T₂-component with T₂ = 26 ms and volume fraction of 0.25 and a short tNAA T₂-component around 15 ms with volume fraction of 0.34. No statistically significant change in Glu, tCr and tNAA signal during stimulation was detected at any TE. The volume fractions of short-T₂ component between rest and active conditions were not statistically different. This study provides evidence for a short T₂-component for Glu, tCr and tNAA but no evidence to support the hypothesis of task-related changes in glutamate distribution between short and long T₂ compartments.