Background & Aim
Two dimensional localised correlation spectroscopy (2D L-COSY) has been applied to evaluate in vivo metabolic activity in many neurological conditions1,2. Reproducibility studies have shown 2D L-COSY is reliable and found to have little variation (<10%) in the detection of both diagonal and cross peaks1,3. However, circadian mediators such as brain temperature, hydration and osmotic regulation can affect metabolic profiles4. The aim of this study was to evaluate the diurnal variability in neuro metabolites using 2D L-COSY in healthy subjects.
Methods
After local ethics approval and informed consent, 2D L-COSY were obtained on 3T MR unit with 64ch coil. Ten healthy subjects (mean age 36.1±7.7 years, 5Male/5Female) were scanned repeatedly over 10-hour period at 0700, 1200 and 1700 on the same day. The 3x3x3 cm3 MRS voxel was located in the posterior cingulate gyrus with first TEinitial of 30ms, TR 1.5sec, 8 averages, t1 delay of 0.8ms, and 96 increments. Braino GE phantom was used for in vitro study. Raw spectral data was processed and analysed with Felix software. The peaks studied were total N-acetylaspartate (t_NAA), choline, myo-inositol, glutamate+glutamine (Glx), glutathione and glucose. All peaks were normalised to creatine as an internal reference. One-way repeated measures ANOVA was used to evaluate the effects of time of day on metabolite levels.
Results and Discussion
In vitro results showed no significant differences in metabolite ratios (p>0.12) between any time points. In vivo results showed there was statistically significant increase in metabolite levels between 0700 and 1700 for all metabolites (p≤0.05, F>3.88). Glucose (34%) and t_NAA (1.9%) showed the largest and smallest percentage changes respectively. Although the subjects were not controlled for diet or hydration, the possible increase in metabolic changes may be due to osmotic regulatory processes and short-term physiological changes. This study has significant implications for future longitudinal studies using 2D L-COSY where time of the day needs consideration when quantifying neuro metabolites.