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Object <p>This study exploits newly developed dynamic indirect <sup>1</sup>H-[<sup>2</sup>H]-FID-MRSI at 9.4&#xa0;T, combined with a dedicated metabolic model, to enable regional and quantitative characterization of glucose oxidative metabolism flux in the rat brain with minimal metabolic assumptions, by measuring both <sup>2</sup>H-labelled Glx turnover and pool size along a controlled <sup>2</sup>H-Glc infusion protocol.</p> Materials and Methods <p>Seven rats underwent dynamic 2D <sup>1</sup>H-FID-MRSI during a 2-h infusion of [6,6’-<sup>2</sup>H₂] glucose. Consecutive 13-min acquisitions quantified Glx-C4 <sup>1</sup>H-signal decay, converted to <sup>2</sup>H-Glx concentrations using baseline metabolite pool sizes. A four-pool kinetic model including <sup>2</sup>H-label loss was fitted to regional turnover curves to estimate oxidative flux (V<sub>gt</sub>) and pyruvate dilution (Kdil). Model performance and parameter robustness were assessed with Monte-Carlo simulations.</p> Results <p>In vivo <sup>2</sup>H-Glx turnover showed a saturated exponential rise (~ 60&#xa0;min), with a labelling plateau higher in striatum (1.85&#xa0;μmol/g) than hippocampus (1.55&#xa0;μmol/g). Metabolic modelling provided region-specific oxidative fluxes: V<sub>gt</sub> = 0.53 ± 0.15&#xa0;μmol/g/min (hippocampus) and V<sub>gt</sub> = 0.81 ± 0.12&#xa0;μmol/g/min (striatum), with consistent Kdil across regions. Simulations confirmed a good model robustness in retrieving V<sub>gt</sub> over a large range of experimental conditions.</p> Discussion <p>This work shows the potential of indirect dynamic <sup>1</sup>H-[<sup>2</sup>H]-FID-MRSI for quantitative metabolic flux mapping of cerebral glucose oxidative metabolism.</p>

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Metabolic modelling and time-resolved mapping of glucose oxidative metabolism in the rat brain by indirect deuterium detection with 1H-FID-MRSI at 9.4 T

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Alessio Siviglia,
  • Gianna Nossa,
  • Brayan Alves,
  • Fabian Niess,
  • Anna Duguid,
  • Zenon Starčuk Jr.,
  • Wolfgang Bogner,
  • Bernhard Strasser,
  • Cristina Cudalbu,
  • Bernard Lanz

摘要

Object

This study exploits newly developed dynamic indirect 1H-[2H]-FID-MRSI at 9.4 T, combined with a dedicated metabolic model, to enable regional and quantitative characterization of glucose oxidative metabolism flux in the rat brain with minimal metabolic assumptions, by measuring both 2H-labelled Glx turnover and pool size along a controlled 2H-Glc infusion protocol.

Materials and Methods

Seven rats underwent dynamic 2D 1H-FID-MRSI during a 2-h infusion of [6,6’-2H₂] glucose. Consecutive 13-min acquisitions quantified Glx-C4 1H-signal decay, converted to 2H-Glx concentrations using baseline metabolite pool sizes. A four-pool kinetic model including 2H-label loss was fitted to regional turnover curves to estimate oxidative flux (Vgt) and pyruvate dilution (Kdil). Model performance and parameter robustness were assessed with Monte-Carlo simulations.

Results

In vivo 2H-Glx turnover showed a saturated exponential rise (~ 60 min), with a labelling plateau higher in striatum (1.85 μmol/g) than hippocampus (1.55 μmol/g). Metabolic modelling provided region-specific oxidative fluxes: Vgt = 0.53 ± 0.15 μmol/g/min (hippocampus) and Vgt = 0.81 ± 0.12 μmol/g/min (striatum), with consistent Kdil across regions. Simulations confirmed a good model robustness in retrieving Vgt over a large range of experimental conditions.

Discussion

This work shows the potential of indirect dynamic 1H-[2H]-FID-MRSI for quantitative metabolic flux mapping of cerebral glucose oxidative metabolism.