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

Abstract

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=- 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.