Deuterium Metabolic Imaging of Alzheimer Disease at 3-T Magnetic Field Strength: A Pilot Case-Control Study

Abstract

Background: Impaired glucose metabolism is characteristic of several dementia types, preceding cognitive symptoms and structural brain changes. Reduced glucose uptake detection in specific brain regions using 18F-fluorodeoxyglucose-PET (18F-FDG-PET) is a valuable diagnostic marker in Alzheimer’s disease (AD). However, 18F-FDG-PET use in clinical practice may be limited by equipment availability and high cost. Purpose: To test the feasibility of using MRI-based deuterium metabolic imaging (DMI) at a clinical magnetic-field strength (3 T) to detect and localize changes in glucose and its metabolites in patients with a clinical diagnosis of AD. Materials and Methods: Participants were recruited for this prospective case‒control pilot study between March 2021 and February 2023. DMI was performed at 3 T using a custom birdcage head coil following oral administration of deuterium-labeled glucose (0.75 g/kg). Unlocalized whole-brain magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic images (MRSI, cubic 3.2 cm voxel) were acquired. Ratios of 2H-glucose, 2H-glutamate/glutamine (2H-Glx) and 2H-lactate spectroscopic peak signals to 2H-water peak signal were calculated for the whole-brain MRS, and for individual MRSI voxels. Results: A total of 19 participants, including 10 participants with AD (mean age, 68 years ±5 [SD]; 8 males) and 9 cognitively healthy control participants (mean age, 70 years ± 6 [SD]; 6 males) were evaluated. Whole-brain spectra demonstrated a reduced ratio of the peak 2H-Glx to 2H-glucose signals in participants with AD compared with control participants (0.41±0.09 vs. 0.58±0.20, P=.04), suggesting an impairment of oxidative glucose metabolism in AD. However, there was no evidence of localization of these changes to the expected regions of metabolic impairment on MRSI presumably due to insufficient spatial resolution. Conclusion: DMI at 3 T demonstrated impairment of oxidative glucose metabolism in patients with Alzheimer’s disease but no evidence of regional signal differences.