Investigation of NAA and NAAG dynamics underlying visual stimulation using MEGA-PRESS in a functional MRS experiment.

N-acetyl-aspartate (NAA) is responsible for the majority of the most prominent peak in (1)H-MR spectra, and has been used as diagnostic marker for several pathologies. However, ~10% of this peak can be attributed to N-acetyl-aspartyl-glutamate (NAAG), a neuropeptide whose release may be triggered by intense neuronal activation. Separate measurement of NAA and NAAG using MRS is difficult due to large superposition of their spectra. Specifically, in functional MRS (fMRS) experiments, most work has evaluated the sum NAA+NAAG, which does not appear to change during experiments. The aim of this work was to design and perform an fMRS experiment using visual stimulation and a spectral editing sequence, MEGA-PRESS, to further evaluate the individual dynamics of NAA and NAAG during brain activation. The functional paradigm used consisted of three blocks, starting with a rest (baseline) block of 320 s, followed by a stimulus block (640 s) and a rest block (640 s). Twenty healthy subjects participated in this study. On average, subjects followed a pattern of NAA decrease and NAAG increase during stimulation, with a tendency to return to basal levels at the end of the paradigm, with a peak NAA decrease of -(21±19)% and a peak NAAG increase of (64±62)% (Wilcoxon test, p<0.05). These results may relate to: 1) the only known NAAG synthesis pathway is from NAA and glutamate; 2) a relationship between NAAG and the BOLD response.

(31)P-MRS using visual stimulation protocols with different durations in healthy young adult subjects.

Phosphorus magnetic resonance spectroscopy ((31)P-MRS) combined with visual stimulation in functional experiments allows the non-invasive dynamic study of brain energy metabolism. (31)P-MRS has been applied to several diseases and to healthy subjects, but works have shown variable findings and non-reproducible results, possibly caused by low numbers of subjects combined with different stimulation paradigms. In the present work, we used (31)P-MRS at 3 T with two different visual stimulation protocols with different block duration ("short" and "long") to evaluate metabolic changes under different workloads in 38 healthy subjects. We found a 15 % (short protocol-blocks of 1.5 min stimulation) and 3 % (long protocol-blocks of 5 min stimulation) increase in the inorganic phosphate (Pi) to α-adenosine triphosphate (α-ATP) ratio, and a 5 % (short protocol) and 2 % (long protocol) decrease in the nicotinamide adenine nucleotide (NADH + NAD(+)) to α-ATP ratio. The NADH + NAD(+) results are, to the best of our knowledge, the first functional magnetic resonance spectroscopy in vivo assessment of these compounds, but their interpretation is difficult since they cannot be separately quantified at 3 T. Our results show that longer stimulations produce smaller concentration changes in Pi/α-ATP and (NADH + NAD(+))/α-ATP ratios, which suggests a possible adaptation effect during longer stimulations that leads metabolic concentrations towards the initial equilibrium.