Assessment of Glucose Metabolism In Vivo in the Human Frontal Lobe Using Interleaved 1 H and 13 C MRS at 7T: Toward Clinical Translation
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Background
Mitochondrial dysfunction and abnormal cerebral energy metabolism are implicated in many neuropsychiatric and neurodegenerative disorders. 13 C magnetic resonance spectroscopy (MRS), combined with 13 C-labeled substrate infusion, offers a non-ionizing, minimally invasive method for assessing fluxes through the main cerebral energy metabolism pathways. However, its human application at 7 T has not been fully established, especially within the frontal lobe.
Purpose
To explore a clinically translatable interleaved 1 H/ 13 C MRS protocol for quantification of cerebral glucose uptake and downstream metabolism at 7 T, and to estimate the tricarboxylic acid (TCA) cycle flux (V TCA ) for validation.
Study Type
Prospective.
Population
Three young healthy volunteers.
Field Strength/Sequence
7T; 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 immediately 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.
Data Conclusion
This interleaved 1 H/ 13 C MRS protocol enables minimally invasive quantification of cerebral metabolic fluxes, may provide a useful framework for investigating neuropsychiatric and neurodegenerative diseases at 7 T.
Evidence Level
1.
Technical Efficacy
Stage 1.
