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

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-d₂ ([6,6'-²H₂]glucose), where labelling of the sixth carbon facilitates ²H-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-d₇ ([1,2,3,4,5,6,6'-²H₇]glucose) 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-d₇ ingestion for monitoring glucose metabolism in the human brain. Results were compared to measurements using the same protocol but with oral glucose-d₂. 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-d₇ (7 participants) or glucose-d₂ (8 participants). A visual stimulus was applied for 10 participants. Larger ²H signals were measured following glucose-d₇ ingestion, and whole-brain signal ratios at times of 100 to 120 min after glucose-d₇ or glucose-d₂ 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-d₇, 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-d₇ with DMI can facilitate non-invasive in vivo assessment of metabolism in the human brain, with wide applications in experimental medicine and disease.