Deuterium metabolic imaging and hyperpolarized ¹³C-MRI of the normal human brain at clinical field strength reveals differential cerebral metabolism

Deuterium metabolic imaging (DMI) and hyperpolarized C-13-pyruvate MRI (C-13-HPMRI) are two emerging meth-ods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications in cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, and inborn errors of metabolism. Here we directly compare these two non-invasive methods at 3 T for the first time in humans and show how they simultaneously probe both oxidative and non-oxidative metabolism. DMI was undertaken 1-2 h after oral administration of [6,6'-H-2(2)]glucose, and C-13-MRI was performed immediately following intravenous injection of hyperpolarized [1-C-13]pyruvate in ten and nine normal volunteers within each arm respectively. DMI was used to generate maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine (Glx) and the spectral separation demonstrated that DMI is feasible at 3 T. C-13-HPMRI generated maps of hyperpo-larized carbon-13 labelled pyruvate, lactate, and bicarbonate. The ratio of C-13-lactate/C-13-bicarbonate (mean 3.7 +/- 1.2) acquired with C-13-HPMRI was higher than the equivalent H-2-lactate/H-2-Glx ratio (mean 0.18 +/- 0.09) acquired using DMI. These differences can be explained by the route of administering each probe, the timing of imaging after ingestion or injection, as well as the biological differences in cerebral uptake and cellular physiol-ogy between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and reductive metabolism within a clinically feasible timescale. Fur-thermore, as DMI was undertaken at a clinical field strength within a ten-minute scan time, it demonstrates its potential as a routine clinical tool in the future.