Multimodal neuroimaging provides a highly consistent picture of energy metabolism, validating 31 P MRS for measuring brain ATP synthesis

Neuroimaging methods have considerably developed over the last decades and offer various noninvasive approaches for measuring cerebral metabolic fluxes connected to energy metabolism, including PET and magnetic resonance spectroscopy (MRS). Among these methods, (31)P MRS has the particularity and advantage to directly measure cerebral ATP synthesis without injection of labeled precursor. However, this approach is methodologically challenging, and further validation studies are required to establish (31)P MRS as a robust method to measure brain energy synthesis. In the present study, we performed a multimodal imaging study based on the combination of 3 neuroimaging techniques, which allowed us to obtain an integrated picture of brain energy metabolism and, at the same time, to validate the saturation transfer (31)P MRS method as a quantitative measurement of brain ATP synthesis. A total of 29 imaging sessions were conducted to measure glucose consumption (CMRglc), TCA cycle flux (V(TCA)), and the rate of ATP synthesis (V(ATP)) in primate monkeys by using (18)F-FDG PET scan, indirect (13)C MRS, and saturation transfer (31)P MRS, respectively. These 3 complementary measurements were performed within the exact same area of the brain under identical physiological conditions, leading to: CMRglc = 0.27 +/- 0.07 micromol x g(-1) x min(-1), V(TCA) = 0.63 +/- 0.12 micromol x g(-1) x min(-1), and V(ATP) = 7.8 +/- 2.3 micromol x g(-1) x min(-1). The consistency of these 3 fluxes with literature and, more interestingly, one with each other, demonstrates the robustness of saturation transfer (31)P MRS for directly evaluating ATP synthesis in the living brain.