Measurement of human tricarboxylic acid cycle rates during visual activation by 13C magnetic resonance spectroscopy

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Abstract
Measurement by 13C magnetic resonance spectroscopy (MRS) of the incorporation of label from [1‐13C] glucose, initially into C4 of glutamate, allows the regional tricarboxylic acid (TCA) cycle flux (FTCA) to be determined in the human brain. In this study, a direct 13C MRS approach was used at 3T, with NOE enhancement and 1H decoupling with WALTZ16, to determine basal FTCA in six volunteers. The values found in the visual cortex are similar to those reported in previous 13C MRS studies, and consistent with PET measurements of the cerebral metabolic rate for glucose, CMRglc. In two preliminary activation studies using light emitting diode (LED) goggles flashing at 8 Hz, compared to darkness as control, increases in FTCA were found from 0.60 ± 0.10 to 0.94 ± 0.03 μmol/min/g (56%) and from 0.34 ± 0.14 to 0.56 ± 0.07 μmol/min/g (65%). These are upper estimates, but they are similar to the increases in CMRglc reported in PET studies, and strongly suggest, in contrast to these PET studies, that cerebral glucose is metabolized oxidatively, even during intense visual stimulation. This is supported by the observation that very little 13C label is incorporated into C3 lactate, as would be expected if glucose were metabolized anaerobically. There is evidence for incorporation of glucose into cerebral glycogen, but this is a relatively minor component of cerebral glucose metabolism.