{"doi":"10.1101/2022.10.25.22281503","title":"Non-invasive three-dimensional 1H-MR Spectroscopic Imaging of human brain glucose and neurotransmitter metabolism using deuterium labeling at 3T","abstract":"Abstract Objectives Non-invasive, affordable, and reliable mapping of brain glucose metabolism is of critical interest for clinical research and routine application as metabolic impairment is linked to numerous pathologies e.g., cancer, dementia and depression. A novel approach to map glucose metabolism non-invasively in the human brain and separate normal oxidative from pathologic anaerobic pathways has been presented recently on experimental MR scanners using direct or indirect detection of deuterium-labeled glucose and downstream metabolites such as glutamate, glutamine and lactate. The aim of this study was to demonstrate the feasibility to non-invasively detect deuterium labeled downstream glucose metabolites indirectly in the human brain via 3D proton ( 1 H) MR spectroscopic imaging on a clinical 3T MR scanner without additional hardware. Materials and Methods This prospective, institutional review board approved study was performed in seven healthy volunteers (mean age, 31±4 years, 5 m/ 2 f) following written informed consent. After overnight fasting and oral deuterium-labeled glucose administration 3D metabolic maps were acquired every ∼4 min with ∼0.24 ml isotropic spatial resolution using real-time motion-, shim- and frequency-corrected echo-less 3D 1 H-MR Spectroscopic Imaging. Time courses were analyzed using linear regression and non-parametric statistical tests. Deuterium labeled glucose and downstream metabolites were detected indirectly via their respective signal decrease in dynamic 1 H MR spectra due to deuterium to proton exchange in the molecules. Results Sixty-five minutes after deuterium-labeled glucose administration, glutamate+glutamine (Glx) signal intensities decreased in gray/white matter (GM,WM) by -15±2%,( p =0.02)/-14±3%,( p =0.02), respectively. Strong negative correlation between Glx and time was observed in GM/WM (r=-0.71 p <0.001)/(r=-0.67, p <0.001) with 38±18% ( p =0.02) steeper slopes, indicating faster metabolic activity in GM compared to WM. Other non-labeled metabolites showed no significant changes. Conclusion Our approach translates deuterium metabolic imaging to widely available clinical routine MR scanners without specialized hardware offering a safe, affordable, and versatile (other substances than glucose can be labeled) approach for non-invasive imaging of glucose and neurotransmitter metabolism in the human brain.","journal":"medRxiv","year":2022,"id":312546,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1009979,"name":"Lukas Hingerl","orcid":"0000-0003-1808-8349","position":1,"is_corresponding":false},{"id":410063,"name":"Bernhard Strasser","orcid":"0000-0001-9542-3855","position":2,"is_corresponding":false},{"id":481269,"name":"Petr Bednařík","orcid":"0000-0002-8828-7661","position":3,"is_corresponding":false},{"id":1009980,"name":"Dario Goranovic","orcid":"0000-0002-0280-2889","position":4,"is_corresponding":false},{"id":1009981,"name":"Eva Niess","orcid":"0000-0001-9956-1470","position":5,"is_corresponding":false},{"id":856611,"name":"Gilbert Hangel","orcid":"0000-0002-3986-3159","position":6,"is_corresponding":false},{"id":262950,"name":"Martin Krššák","orcid":"0000-0001-9717-803X","position":7,"is_corresponding":false},{"id":1009982,"name":"Benjamin Spurny‐Dworak","orcid":"0000-0003-0230-1918","position":8,"is_corresponding":false},{"id":1009983,"name":"Thomas Scherer","orcid":"0000-0003-4980-706X","position":9,"is_corresponding":false},{"id":342691,"name":"Rupert Lanzenberger","orcid":"0000-0003-4641-9539","position":10,"is_corresponding":false},{"id":256334,"name":"Wolfgang Bogner","orcid":"0000-0002-0130-3463","position":11,"is_corresponding":false},{"id":1009978,"name":"Fabian Niess","orcid":"0000-0003-1235-7595","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:33:36.072096Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}