Non-invasive measurement of neurotransmitter-specific glucose metabolism in the human brain using proton-observed proton-edited 13C-MRS (POPE13C-MRS)

Cherix, A.; Haermson, O.; Tachrount, M.; Campbell, J.; Clarke, W. T.; Tyler, D.; Lerch, J.; Stagg, C. J.

doi:10.64898/2026.03.13.711600

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bioRxiv · 10.64898/2026.03.13.711600

Non-invasive measurement of neurotransmitter-specific glucose metabolism in the human brain using proton-observed proton-edited 13C-MRS (POPE13C-MRS)

Cherix, A.·Haermson, O.·Tachrount, M.·Campbell, J.·Clarke, W. T.·Tyler, D.·Lerch, J.·Stagg, C. J.

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Abstract

Non-invasive measurement of neurotransmitter-specific glucose metabolism in the human brain remains a major challenge, limiting mechanistic insight into excitatory-inhibitory imbalance across neurological and psychiatric disorders. Existing approaches either lack neurotransmitter specificity or require specialised hardware that constrains clinical applicability. Here, we introduce proton-observed proton-edited 13C magnetic resonance spectroscopy (POPE13C-MRS), an approach that enables non-invasive detection of glutamate, GABA, and lactate metabolism using standard proton MRI hardware. The method combines administration of 13C-labelled glucose with targeted proton editing to detect 1H-13C satellite resonances. Using a cross-species proof-of-concept approach, we demonstrate consistent detection of neurotransmitter-specific 13C labelling in mice and feasibility in the human brain at ultra-high field. POPE13C-MRS provides a readout of glutamatergic and GABAergic metabolism, enabling in vivo assessment of excitatory-inhibitory metabolic balance. This establishes a means for probing neurometabolic coupling with potential applications in translational and clinical neuroscience.

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Cherix, A., Haermson, O., Tachrount, M., Campbell, J., Clarke, W. T., Tyler, D., Lerch, J., Stagg, C. J.. 2026-03-17. Non-invasive measurement of neurotransmitter-specific glucose metabolism in the human brain using proton-observed proton-edited 13C-MRS (POPE13C-MRS). https://doi.org/10.64898/2026.03.13.711600

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