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

M. Chaumeil J. Valette M. Guillermier 1 E. Brouillet 1 F. Boumezbeur A.-S. Herard 1 G. Bloch P. Hantraye 1 V. Lebon
1 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
MIRCEN - Service MIRCEN : DRF/JACOB, UP11 - Université Paris-Sud - Paris 11, CNRS - Centre National de la Recherche Scientifique : UMR 9199
Abstract : 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 (VTCA), and the rate of ATP synthesis (VATP) 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 mol⅐g ؊1 ⅐min ؊1 , VTCA ‫؍‬ 0.63 ؎ 0.12 mol⅐g ؊1 ⅐min ؊1 , and VATP ‫؍‬ 7.8 ؎ 2.3 mol⅐g ؊1 ⅐min ؊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.
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M. Chaumeil, J. Valette, M. Guillermier, E. Brouillet, F. Boumezbeur, et al.. Multimodal neuroimaging provides a highly consistent picture of energy metabolism, validating 31P MRS for measuring brain ATP synthesis. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2009, 106 (10), pp.3988-3993. ⟨10.1073/pnas.0806516106⟩. ⟨hal-02155689⟩

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