Deuterium metabolic imaging and hyperpolarized¹³C-MRI of the normal human brain at clinical field strength reveals differential cerebral metabolism

Abstract

Deuterium 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 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.

Deuterium metabolic imaging of the human brain in vivo at 7 T

“…An alternative RF coil design for whole brain DMI with minimal differences in SNR between the periphery and the center could be a birdcage coil. Although successfully used for DMI at 3 T, 18 the birdcage coil comes at the cost of a reduced SNR in the periphery of the brain compared to the coil design used in the present study.…”

Noninvasive 3-Dimensional 1H-Magnetic Resonance Spectroscopic Imaging of Human Brain Glucose and Neurotransmitter Metabolism Using Deuterium Labeling at 3T

“…4 Deuterium metabolic imaging detects deuterium enrichment in the brain tissue directly via 2 H-MR spectroscopy (MRS), whereas, indirectly, QELT detects a decrease in signal intensities in conventional 1 H-MR spectra due to deuterium-to-proton exchange of labeled and unlabeled molecules, comparably as already performed using 13 C-labeled Glc. 11 Recently, DMI has been translated to clinical field strength of 3T 12 with a nominal isotropic resolution of 33 mL and an acquisition time of 10 minutes for each 3-dimensional (3D) dataset. Quantitative exchanged label turnover features higher signal-to-noise ratio (SNR) and spatial resolution (0.12 mL) with shorter acquisition times (~3 minutes 7 ) compared with DMI, while additionally detecting nonlabeled metabolites, but so far has been applied in humans only at ultrahigh field strength of ≥7T.…”

Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI)

“…DMI acquisition has already been used in human subjects by different research groups and at different magnetic field strengths, and is thus proven to be translatable (Ruhm et al, 2021;Kaggie et al, 2022;Roig et al, 2022). Examples of DMI combined with oral intake of deuterated glucose in patients with brain tumors has also shown high tumor-to-brain image contrast (De Feyter et al, 2018).…”