Abstract
<jats:p> Background Mitochondrial dysfunction and abnormal cerebral energy metabolism are implicated in many neuropsychiatric and neurodegenerative disorders. <jats:sup>13</jats:sup> C magnetic resonance spectroscopy (MRS), combined with <jats:sup>13</jats:sup> 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 <jats:sup>1</jats:sup> H/ <jats:sup>13</jats:sup> 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 <jats:sub>TCA</jats:sub> ) for validation. Study Type Prospective. Population Three young healthy volunteers. Field Strength/Sequence 7T; ACE-STEAM (indirect <jats:sup>1</jats:sup> H-[ <jats:sup>13</jats:sup> C]) and ISIS-DEPT (direct <jats:sup>13</jats:sup> C-[ <jats:sup>1</jats:sup> H]). Assessment ACE-STEAM and ISIS-DEPT were applied to acquire the time-resolved spectra in the frontal lobe. <jats:sup>13</jats:sup> C-labeled glucose, glutamate, and glutamine fractional enrichment time courses were quantified to estimate V <jats:sub>TCA</jats:sub> 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 <jats:sup>13</jats:sup> C traces. Uncertainty of the estimated metabolic fluxes was evaluated using Monte-Carlo simulations. Results [1- <jats:sup>13</jats:sup> C]-glucose (GlcC1) was detected immediately on <jats:sup>13</jats:sup> C MR spectra, followed by <jats:sup>13</jats:sup> C-labeled GluH4 and GlnH4 and then GlxH3 can be quantified on <jats:sup>1</jats:sup> 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 VTCA was 0.66 ± 0.07 μmol/g/min. Data Conclusion This interleaved <jats:sup>1</jats:sup> H/ <jats:sup>13</jats:sup> 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. </jats:p>