Abstract
Impaired glucose metabolism in the brain has been linked to several neurological disorders. Positron emission tomography and carbon-13 magnetic resonance spectroscopic imaging (MRSI) can be used to quantify the metabolism of glucose, but these methods involve exposure to radiation, cannot quantify downstream metabolism, or have poor spatial resolution. Deuterium MRSI (2H-MRSI) is a non-invasive and safe alternative for the quantification of the metabolism of 2H-labelled substrates such as glucose and their downstream metabolic products, yet it can only measure a limited number of deuterated compounds and requires specialized hardware. Here we show that proton MRSI (1H-MRSI) at 7 T has higher sensitivity, chemical specificity and spatiotemporal resolution than 2H-MRSI. We used 1H-MRSI in five volunteers to differentiate glutamate, glutamine, γ-aminobutyric acid and glucose deuterated at specific molecular positions, and to simultaneously map deuterated and non-deuterated metabolites. 1H-MRSI, which is amenable to clinically available magnetic-resonance hardware, may facilitate the study of glucose metabolism in the brain and its potential roles in neurological disorders.
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Data availability
The main data supporting the results in this study are available within the paper and its Supplementary Information. Source data for Figs. 1, 4 and 6 and for Supplementary Figs. 1–3 and 5 are provided with this paper. The raw data acquired in the study are too large to be publicly shared, yet they are available for research purposes from the corresponding authors on reasonable request. The data generated by post-processing methods (that is, metabolite maps, MR spectra and outcomes of their quantification in the LCModel) are available at https://doi.org/10.5281/zenodo.5705959. The shared data are in the minc, niifti and MRSpa data formats. A priori information (‘the basis sets’) needed for MRS/MRSI data quantification in the LCModel is also available via the same link.
Code availability
The custom code for the time-course analysis using linear and exponential fits was performed using custom-made Python code (v3.10) available at https://github.com/MRSI-HFMR-GroupVienna/DeuteriumToProtonExchangeMRS.
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Acknowledgements
We thank P. Bolan of the Center for Magnetic Resonance Research, University of Minnesota, and C. Rogers, University of Cambridge, for providing a tool to store and apply 7 T B0-shims for the 7 T MR scanner; V. Mlynarik for helpful discussions; and the study participants whose help is greatly appreciated. P.B. was supported by the European Union’s Horizon 2020 research and innovation programme under a Marie Skłodowska-Curie grant (agreement no. 846793), and by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (no. 27238). A.S. received funding from the European Union’s Horizon 2020 research and from an innovation programme under a Marie Skłodowska-Curie grant (agreement no. 794986). The authors acknowledge support from the Austrian Science Fund (FWF) (grants P 30701 and KLI 718 to W.B., I 6037 to B.S., KLI 782 to T.S., and KLI 646 to G.H.). W.B. acknowledges the support of the following NIH grant: R01EB031787. D.K.D. acknowledges support from the following National Institutes of Health grants: BTRC P41 EB027061 and P30 NS076408
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P.B., A.S. and W.B. wrote the manuscript draft. P.B., D.G. and L.H. acquired the data. P.B., D.G., F.N., L.H., D.K.D., B.S., B.S-D., G.H. and A.S. processed the data. P.B., W.B., T.S. and R.L. conceptualized the study design. P.B., A.S., W.B. and R.L. obtained funding. M.K. and S.T. contributed to data interpretation. P.B. and W.B are guarantors of the integrity of the entire study. All authors edited and approved the submitted version of the manuscript.
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R. Lanzenberger received travel grants and/or conference speaker honoraria within the past three years from Bruker BioSpin MR and Heel, and has served as a consultant for Ono Pharmaceutical. He also received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MR and is a shareholder of the start-up company BM Health GmbH since 2019. The other authors declare no competing interests.
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MRS data quantified with the LCModel.
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MRS data quantified with the LCModel, including timing.
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MRS data quantified with the LCModel, including timing.
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Bednarik, P., Goranovic, D., Svatkova, A. et al. 1H magnetic resonance spectroscopic imaging of deuterated glucose and of neurotransmitter metabolism at 7 T in the human brain. Nat. Biomed. Eng 7, 1001–1013 (2023). https://doi.org/10.1038/s41551-023-01035-z
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DOI: https://doi.org/10.1038/s41551-023-01035-z
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