Journal Article

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

Strasser, Bernhard, Gruber, Stephan, Hingerl, Lukas, Hangel, Gilbert, Spurny-Dworak, Benjamin, Scherer, Thomas, Bogner, Wolfgang, Trattnig, Siegfried, Krššák, Martin, Motyka, Stanislav, Lanzenberger, Rupert, Niess, Eva, Niess, Fabian

2023

Overview

•Imaging of brain glucose metabolism using MR spectroscopic imaging and 2H labeling.•Direct (2H DMI at 7T) and indirect detection (1H QELT at 3T) were compared.•Comparable enrichment of labeled compounds was observed with both methods.•Reproduced 7T DMI results using 1H QELT at clinical 3T without additional hardware. 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′-2H2]-glucose, its uptake and synthesis of downstream metabolites can be mapped via direct or indirect detection of deuterium resonances using 2H MRSI (DMI) and 1H 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. Five volunteers (4 m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8 g/kg oral [6,6′-2H2]-glucose administration using time-resolved 3D 2H FID-MRSI with elliptical phase encoding at 7T and 3D 1H FID-MRSI with a non-Cartesian concentric ring trajectory readout at clinical 3T. One hour after oral tracer administration regionally averaged deuterium labeled Glx4 concentrations and the dynamics were not significantly different over all participants between 7T 2H DMI and 3T 1H 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 Glc6 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 2H and 1H 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). This study demonstrates that indirect detection of deuterium labeled compounds using 1H 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 2H 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.

• Publisher: Elsevier Inc,Elsevier Limited,Elsevier
• Subject: Alzheimer's disease / Automation / Brain - diagnostic imaging / Brain - metabolism / Deuterium - metabolism / Deuterium labeled glucose, Clinical 3T / Deuterium metabolic imaging / Glucose / Glucose - metabolism / Humans / Intravenous administration / Magnetic fields / Magnetic Resonance Imaging - methods / Magnetic resonance spectroscopy / Metabolism / Metabolites / MR spectroscopy / Neuroimaging / Quantitative exchange label turnover / Reproducibility / Reproducibility of Results / Scanners / Three dimensional imaging