Assessment of Glucose Metabolism in Vivo in the Human Frontal Lobe Using Interleaved 1 H and 13 C MRS at 7T

ABSTRACT Background 13 C magnetic resonance spectroscopy (MRS), combined with 13 C‐labeled substrate infusion, offers a nonionizing, minimally invasive method for assessing fluxes through the main cerebral energy metabolism pathways. However, its human application at 7T has not been fully established, especially within the frontal lobe, where alterations are linked to various neurological and psychiatric disorders. Purpose To explore the feasibility of the interleaved 1 H / 13 C MRS protocol for quantification of cerebral glucose uptake and downstream metabolism at 7T, and to estimate the tricarboxylic acid ( TCA ) cycle flux ( V TCA ) for validation. Study Type Prospective. Population Three healthy volunteers (Two females and one male). Field Strength/Sequence 7T; single voxel spectroscopy: ACE‐STEAM (indirect 1 H‐[ 13 C]) and ISIS‐DEPT (direct 13 C‐[ 1 H]). Assessment ACE‐STEAM and ISIS‐DEPT were applied to acquire the time‐resolved spectra in the frontal lobe. 13 C‐labeled glucose, glutamate, and glutamine fractional enrichment time courses were quantified to estimate V TCA through the one‐compartment model. Statistical Tests The relative estimated fitting uncertainties (EFUs) were reported for the processed spectra. Nonlinear least squares minimization was used for flux fitting of 13 C traces. Uncertainty of the estimated metabolic fluxes was evaluated using Monte Carlo simulations. Results [1‐ 13 C]‐glucose (GlcC1) was detected within 6 min on 13 C MR spectra, followed by 13 C‐labeled GluH4 and GlnH4, and then GlxH3 can be quantified on 1 H MR spectra. End‐of‐infusion mean enrichments were 17% (GluH4), 13% (GlnH4), and 7% (GlxH3). Brain glucose concentration ranged 1.86–2.94 mM, with 61% of the mean enrichment in C1. Group‐average V TCA was 0.66 ± 0.07 μmol/g/min ( n = 3). Data Conclusion This interleaved 1 H/ 13 C MRS protocol, combined with 13 C‐labeled glucose infusion, enables minimally invasive quantification of cerebral metabolic fluxes. As a proof‐of‐concept feasibility study in a small healthy volunteer cohort, it may provide a useful framework for investigating neuropsychiatric and neurodegenerative diseases at 7T. Evidence Level 1. Technical Efficacy Stage 1.