Non-invasive three-dimensional 1H-MR Spectroscopic Imaging of human brain glucose and neurotransmitter metabolism using deuterium labeling at 3T

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.