Advancing Deuterium MRI to Track Human Cerebral Glucose Metabolism at 7 T: A Comparison of Glucose‐d 2 and Glucose‐d 7 Ingestion

ABSTRACT Deuterium metabolic imaging (DMI) allows non‐invasive dynamic in vivo assessment of transport, uptake and metabolism of deuterated molecules. To date, DMI experiments in humans have involved ingestion of glucose‐d 2 (6,6’‐ 2 H₂glucose), where labelling of the sixth carbon facilitates 2 H‐label transfer to pyruvate, then to lactate (Lac) via lactate dehydrogenase, or to glutamate and glutamine (Glx) via the tricarboxylic acid cycle. There are advantages to using glucose‐d 7 (1,2,3,4,5,6,6’‐ 2 H₇glucose) for DMI as this should yield larger signals from glucose and downstream metabolites, including deuterated water (HDO). Here, we evaluated DMI at 7 T following glucose‐d 7 ingestion for monitoring glucose metabolism in the human brain. Results were compared to measurements using the same protocol but with oral glucose‐d 2 . Fifteen healthy volunteers participated in the study, which involved initial measurements at natural abundance, followed by 90 min of acquisition after ingestion of 0.75 g/kg glucose‐d 7 (7 participants) or glucose‐d 2 (8 participants). A visual stimulus was applied for 10 participants. Larger 2 H signals were measured following glucose‐d 7 ingestion, and whole‐brain signal ratios at times of 100 to 120 min after glucose‐d 7 or glucose‐d 2 ingestion for HDO, Glx and lactate (with potential contamination from lipid signals) were 1.8 ± 0.3, 1.7 ± 0.3 and 1.6 ± 0.3, respectively. At natural abundance, the SNR of the HDO signal in the CSI data was 14 ± 1. For both isotopologues, the glucose signal peaked ~80 min after ingestion, while Glx, lactate + lipid and HDO signals increased throughout the measurement period. Estimated cerebral concentrations of HDO were larger for glucose‐d 7 , but similar concentrations were found for glucose, Glx and lactate. No significant difference in signal or concentration between visually stimulated and unstimulated participants was found. These findings suggest that glucose‐d 7 with DMI can facilitate non‐invasive in vivo assessment of metabolism in the human brain, with wide applications in experimental medicine and disease.