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’-(2)H(2)]-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 (4m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8g/kg oral [6,6’-(2)H(2)]-glucose administration using time-resolved 3D (2)H FID-MRSI with elliptical phase encoding 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 Glx(4) 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±0.15 vs. 1.38±0.26 mM, p=0.65 & 21±3 vs. 26±3 μM/min, p=0.22) and WM (1.10±0.13 vs. 0.91±0.24 mM, p=0.34 & 19±2 vs. 17±3 μM/min, p=0.48). Also, the observed time constants of dynamic Glc(6) data in GM (24±14 vs. 19±7 min, p=0.65) and WM (28±19 vs. 18±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 Glx(4) 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 Glc(6) data GM (r=−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.