Human Brain Deuterium Metabolic Imaging at 7 T: Impact of Different [6,6'-2H2]Glucose Doses

Abstract

Background: Deuterium metabolic imaging (DMI) is an innovative, noninvasive metabolic MR imaging method conducted after administration of ²H-labeled substrates. DMI after [6,6'-²H₂]glucose consumption has been used to investigate brain metabolic processes, but the impact of different [6,6'-²H₂]glucose doses on DMI brain data is not well known.

Purpose: To investigate three different [6,6'-²H₂]glucose doses for DMI in the human brain at 7 T.

Study type: Prospective.

Population: Six healthy participants (age: 28 ± 8 years, male/female: 3/3).

Field strength/sequence: 7 T, 3D ²H free-induction-decay (FID)-magnetic resonance spectroscopic imaging (MRSI) sequence.

Assessment: Three subjects received two different doses (0.25 g/kg, 0.50 g/kg or 0.75 g/kg body weight) of [6,6'-²H₂]glucose on two occasions and underwent consecutive ²H-MRSI scans for 120 minutes. Blood was sampled every 10 minutes during the scan, to determine plasma glucose levels and plasma ²H-Glucose atom percent excess (APE) (part-1). Three subjects underwent the same protocol once after receiving 0.50 g/kg [6,6'-²H₂]glucose (part-2).

Statistical test: Mean plasma ²H-Glucose APE and glucose plasma concentrations were compared using one-way ANOVA. Brain ²H-Glc and brain ²H-Glx (part-1) were analyzed with a two-level Linear Mixed Model. In part-2, a General Linear Model was used to compare brain metabolite signals. Statistical significance was set at P < 0.05.

Results: Between 60 and 100 minutes after ingesting [6,6'-²H₂]glucose, plasma ²H-Glc APE did not differ between 0.50 g/kg and 0.75 g/kg doses (P = 0.961), but was significantly lower for 0.25 g/kg. Time and doses significantly affected brain ²H-Glucose levels (estimate ± standard error [SE]: 0.89 ± 0.01, 1.09 ± 0.01, and 1.27 ± 0.01, for 0.25 g/kg, 0.50 g/kg, and 0.75 g/kg, respectively) and brain ²H-Glutamate/Glutamine levels (estimate ± SE: 1.91 ± 0.03, 2.27 ± 0.03, and 2.46 ± 0.03, for 0.25 g/kg, 0.50 g/kg, and 0.75 g/kg, respectively). Plasma ²H-Glc APE, brain ²H-Glc, and brain ²H-Glx levels were comparable among subjects receiving 0.50 g/kg [6,6'-²H₂]glucose.

Data conclusion: Brain ²H-Glucose and brain ²H-Glutamate/Glutamine showed to be [6,6'-²H₂]glucose dose dependent. A dose of 0.50 g/kg demonstrated comparable, and well-detectable, ²H-Glucose and ²H-Glutamate/Glutamine signals in the brain.

Evidence level: 1 TECHNICAL EFFICACY: Stage 2.

Keywords: 7 T MRI; brain metabolism; deuterium metabolic imaging.

FIGURE 1

Plasma glucose concentration (top row) and plasma ²H‐Glc APE (bottom row) after oral administration (at T = 0 minutes) of [6,6′‐²H₂]glucose, using different doses of [6,6′‐²H₂]glucose in different subjects and during different visits. Bsln = baseline measurement before [6,6′‐²H₂]glucose consumption.

FIGURE 2

²H MR spectra from a one voxel (a) as a function of time, for the scans performed in different subjects in part 1 with three different [6,6′‐²H₂]glucose doses. The ²H‐Glc signal frequency is indicated by the blue dashed line, and the ²H‐Glx signal by the red dashed line (b).

FIGURE 3

(a) Dynamic DMI maps of ²H‐Glc and ²H‐Glx after oral administration of [6,6′‐²H₂]glucose for three subjects (central slice; as illustrated by the T1w image) using different doses of [6,6′‐²H₂]glucose. Metabolite levels were normalized to the baseline HDO signal. (b) Time curves of average (±standard error of the mean) whole brain ²H‐Glc (top row) and ²H‐Glx (bottom row) concentrations (mM).

FIGURE 4

Time curves of (a) plasma glucose concentration (mM), (b) plasma ²H‐Glc APE (%), (c) average whole brain ²H‐Glc (mM), and (d) average whole brain ²H‐Glx (mM) after oral administration (at T = 0 minutes) of [6,6′‐²H₂]glucose, among all subjects consuming a dose of 0.50 g/kg 6,6′‐²H₂]glucose. Bsln = baseline measurement.

FIGURE 5

Correlation between the concentration of plasma ²H‐Glc and brain ²H‐Glc among all subjects. Color dots indicate dose of [6,6′‐²H₂]glucose.