TY - JOUR
T1 - Quantitative mapping of key glucose metabolic rates in the human brain using dynamic deuterium magnetic resonance spectroscopic imaging
AU - Li, Xin
AU - Zhu, Xiao Hong
AU - Li, Yudu
AU - Wang, Tao
AU - Zhang, Guangle
AU - Wiesner, Hannes M.
AU - Liang, Zhi Pei
AU - Chen, Wei
N1 - This work was supported in part by National Institutes of Health (NIH) grants: R01CA240953, U01EB026978, R01NS133006, P41EB027061, and S10OD025256.
PY - 2025/3/1
Y1 - 2025/3/1
N2 - Deuterium (2H) magnetic resonance spectroscopic imaging (DMRSI) is a newly developed technology for assessing glucose metabolism by simultaneously measuring deuterium-labeled glucose and its downstream metabolites (1) and has a potential to provide a powerful neurometabolic imaging tool for quantitative studies of cerebral glucose metabolism involving multiple metabolic pathways in the human brain. In this work, we developed a dynamic DMRSI method that combines advanced radiofrequency coil and postprocessing techniques to substantially improve the imaging signal-to-noise ratio for detecting deuterated metabolites and enable robust dynamic DMRSI of the human brain at 7 T with very high resolution (HR; 0.7 cc nominal voxel and 2.5 min/image) and whole-brain coverage. Utilizing this capability, we were able to map and differentiate metabolite contents and dynamics throughout the human brain following oral administration of deuterated glucose. Furthermore, by introducing a sophisticated kinetic model, we demonstrated that three key cerebral metabolic rates of glucose consumption (CMRGlc), lactate production (CMRLac), and tricarboxylic acid (TCA) cycle (VTCA), as well as the maximum apparent rate of forward glucose transport (Tmax) can be simultaneously imaged in the human brain through a single dynamic DMRSI measurement. The results clearly show that the glucose transport, neurotransmitter turnover, CMRGlc, and VTCA are significantly higher in gray matter than in white matter in the human brain; and the mean metabolic rates and their ratios measured in this study are consistent with the values reported in the literature. The HR dynamic DMRSI methodology presented herein is of great significance and value for the quantitative assessment of human brain glucose metabolism, aerobic glycolysis, and metabolic reprogramming under physiopathological conditions.
AB - Deuterium (2H) magnetic resonance spectroscopic imaging (DMRSI) is a newly developed technology for assessing glucose metabolism by simultaneously measuring deuterium-labeled glucose and its downstream metabolites (1) and has a potential to provide a powerful neurometabolic imaging tool for quantitative studies of cerebral glucose metabolism involving multiple metabolic pathways in the human brain. In this work, we developed a dynamic DMRSI method that combines advanced radiofrequency coil and postprocessing techniques to substantially improve the imaging signal-to-noise ratio for detecting deuterated metabolites and enable robust dynamic DMRSI of the human brain at 7 T with very high resolution (HR; 0.7 cc nominal voxel and 2.5 min/image) and whole-brain coverage. Utilizing this capability, we were able to map and differentiate metabolite contents and dynamics throughout the human brain following oral administration of deuterated glucose. Furthermore, by introducing a sophisticated kinetic model, we demonstrated that three key cerebral metabolic rates of glucose consumption (CMRGlc), lactate production (CMRLac), and tricarboxylic acid (TCA) cycle (VTCA), as well as the maximum apparent rate of forward glucose transport (Tmax) can be simultaneously imaged in the human brain through a single dynamic DMRSI measurement. The results clearly show that the glucose transport, neurotransmitter turnover, CMRGlc, and VTCA are significantly higher in gray matter than in white matter in the human brain; and the mean metabolic rates and their ratios measured in this study are consistent with the values reported in the literature. The HR dynamic DMRSI methodology presented herein is of great significance and value for the quantitative assessment of human brain glucose metabolism, aerobic glycolysis, and metabolic reprogramming under physiopathological conditions.
KW - aerobic glycolysis
KW - cerebral glucose metabolism
KW - dynamic DMRSI
KW - imaging human brain glucose metabolic rates
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U2 - 10.1093/pnasnexus/pgaf072
DO - 10.1093/pnasnexus/pgaf072
M3 - Article
C2 - 40109558
AN - SCOPUS:105000762155
SN - 2752-6542
VL - 4
JO - PNAS Nexus
JF - PNAS Nexus
IS - 3
M1 - pgaf072
ER -