Reproducibility of 3D MRSI for imaging human brain glucose metabolism using direct ( 2 H) and indirect ( 1 H) detection of deuterium labeled compounds at 7T and clinical 3T*

Introduction: Deuterium metabolic imaging (DMI) and quantitative exchange label turnover (QELT) are novel MR spectroscopy techniques for non-invasive imaging of human brain glucose and neurotransmitter metabolism with high clinical potential. Following oral or intravenous administration of non-ionizing [6,6 & PRIME; -2H2]-glucose, its uptake and synthesis of downstream metabolites can be mapped via direct or indirect detection of deuterium resonances using 2 H MRSI (DMI) and 1 H MRSI (QELT), respectively. The purpose of this study was to compare the dynamics of spatially resolved brain glucose metabolism, i.e., estimated concentration enrichment of deuterium labeled Glx (glutamate +glutamine) and Glc (glucose) acquired repeatedly in the same cohort of subjects using DMI at 7T and QELT at clinical 3T. Methods: Five volunteers (4 m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8 g/kg oral [6,6 & PRIME; -2H2]-glucose administration using time-resolved 3D 2 H FID-MRSI with elliptical phase encod-ing at 7T and 3D 1 H FID-MRSI with a non-Cartesian concentric ring trajectory readout at clinical 3T. Results: One hour after oral tracer administration regionally averaged deuterium labeled Glx4 concentrations and the dynamics were not significantly different over all participants between 7T 2 H DMI and 3T 1 H QELT data for GM (1.29 & PLUSMN; 0.15 vs. 1.38 & PLUSMN; 0.26 mM, p = 0.65 & 21 & PLUSMN; 3 vs. 26 & PLUSMN; 3 & mu;M/min, p = 0.22) and WM (1.10 & PLUSMN; 0.13 vs. 0.91 & PLUSMN; 0.24 mM, p = 0.34 & 19 & PLUSMN; 2 vs. 17 & PLUSMN; 3 & mu;M/min, p = 0.48). Also, the observed time constants of dynamic Glc6 data in GM (24 & PLUSMN; 14 vs. 19 & PLUSMN; 7 min, p = 0.65) and WM (28 & PLUSMN; 19 vs. 18 & PLUSMN; 9 min, p = 0.43) dominated regions showed no significant differences. Between individual 2 H and 1 H data points a weak to moderate negative correlation was observed for Glx4 concentrations in GM ( r = -0.52, p < 0.001), and WM ( r = -0.3, p < 0.001) dominated regions, while a strong negative correlation was observed for Glc6 data GM ( r = -0.61, p < 0.001) and WM ( r = -0.70, p < 0.001). Conclusion: This study demonstrates that indirect detection of deuterium labeled compounds using 1 H QELT MRSI at widely available clinical 3T without additional hardware is able to reproduce absolute concentration estimates of downstream glucose metabolites and the dynamics of glucose uptake compared to 2 H DMI data acquired at 7T. This suggests significant potential for widespread application in clinical settings especially in environments with limited access to ultra-high field scanners and dedicated RF hardware.