Time-of-day study on brain metabolism using proton magnetic resonance spectroscopy

Most human physiological processes follow circadian rhythms such as glucose metabolism and neuronal activity, thereby playing a major role in brain metabolism regulation. Proton Magnetic Resonance Spectroscopy (¹H-MRS) has become a valuable tool for quantification of brain metabolism in clinical settings. Nonetheless, only limited evidence of brain metabolism variation throughout the day has been found, restricted to specific brain regions or limited by a sample size. The aim of this study was to investigate time-of-day effect on brain metabolism in ¹H-MRS of different brain regions associated with circadian rhythms in healthy adults. This prospective monocentric study included 39 healthy volunteers aged between 25 and 40 years. They underwent three 3T MRI examinations the same day at 7:30, 13:30 and 17:30. Two CSI MRS sequences were acquired to study brain regions of the basal ganglia and semi-oval center. A linear mixed model was used to investigate differences between session times, sex and brain hemisphere on acquired total Choline (tCho), total N-Acetyl-Aspartate (tNAA), and Lactate (Lac). Models showed a significant decrease in tCho/tNAA in the last session of -1.60% (p = 0.017) and a lower value of tCho/tCr of -9.74% (p = 0.014) and tCho/tNAA of -7.98% (p = 0.044) for women as compared with men. In the right hemisphere a higher value of tNAA/tCr of +2.84% (p < 0.001) was found, while tCho/tNAA was lower by -1.60% (p = 0.003) compared to the left hemisphere. The metabolite ratios under investigation were not affected by circadian rhythms, except for a small decrease of tCho/tNAA at 17:30. However, sex and brain hemispheres had a significant impact on brain metabolism. While brain MRS examination for most common metabolites could be carried out at any time of day, it is still important to consider the patient's sex and the side of the brain being examined.