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 move-
ments between cellular compartments with different T 2 relaxation times. Previous
studies reporting glutamate (Glu) T 2 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 T 2 (<20 ms). Here, we acquire MRS measurements for Glu, (t) total crea-
tine (tCr) and total N-acetylaspartate (tNAA) from the visual cortex in 14 healthy par-
ticipants 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-T 2 compo-
nents of the curve. We fit monoexponential and biexponential Glu, tCr and tNAA T 2
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 T 2-component with T 2 = 10 ms and volume fraction of
0.35, a short tCr T 2-component with T 2 = 26 ms and volume fraction of 0.25 and a
short tNAA T 2-component around 15 ms with volume fraction of 0.34. No statisti-
cally significant change in Glu, tCr and tNAA signal during stimulation was detected
at any TE. The volume fractions of short-T 2 component between rest and active con-
ditions were not statistically different. This study provides evidence for a short T 2-
component for Glu, tCr and tNAA but no evidence to support the hypothesis of task-
related changes in glutamate distribution between short and long T 2 compartments