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

Author:

Kaggie Joshua DORCID,Khan Alixander SORCID,Matys TomaszORCID,Schulte Rolf FORCID,Locke Matthew J,Grimmer AshleyORCID,Frary Amy,Graves Martin JORCID,McLean Mary AORCID,Gallagher Ferdia AORCID

Abstract

AbstractDeuterium metabolic imaging (DMI) and hyperpolarized 13C-pyruvate MRI (13C-HPMRI) are two emerging methods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications for 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 how they simultaneously probe both glycolytic and oxidative metabolism. DMI was undertaken 1-2 hours after oral administration of [6,6’-2H2]glucose, and 13C-MRI was performed immediately following intravenous injection of hyperpolarized [1-13C]pyruvate in ten and nine normal volunteers within each arm. DMI provided maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine. 13C-HPMRI generated maps of hyperpolarized carbon-13 labelled pyruvate, lactate, and bicarbonate. There was clear spectral separation in the spectroscopic imaging data with both DMI and 13C-HPMRI at 3 T. The ratio of 13C-lactate/13C-bicarbonate (mean = 3.7 ± 1.2) acquired with 13C-HPMRI was higher than the equivalent 2H-lactate/2H-Glx ratio (mean = 0.18 ± 0.09) acquired with 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 physiology between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and glycolytic metabolism within a clinically feasible timescale. Furthermore, 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.

Publisher

Cold Spring Harbor Laboratory

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