Magnetic Resonance Spectroscopy for Ketone Bodies

Supplementary Material Figure 1: The region of interest for single voxel spectroscopy was obtained from the frontal lobe. The voxel (red box) was positioned in front of the corpus collosum and was centered on the anterior cingulate gyrus in the A) sagittal and C) axial planes, and on the lateral ventricle in the B) coronal plane.

While ketone pharmacokinetics for human peripheral blood concentrations have been established, until recently ketone pharmacokinetics for the human brain were unknown. Thus, to establish optimal timing for our clinical neuroscience research, we first performed a magnetic resonance spectroscopy (MRS) study (n = 8; μage = 27 ± 5 y; 3 female) to determine the bolus time course in the brain. Using a within-participant time-locked design, as well as weight- and calorie-matched dosing as described below, we measured brain glucose and β-hydroxybutyrate at baseline, then every 5 min for 90 min after administering each bolus. As per SI Appendix, Fig. S2, MRS showed glucose and ketones reaching peak concentrations in the brain at ∼30 min postbolus. Of the two fuel types, glucose was confirmed to be shorter acting and more volatile compared to ketones (postpeak coefficient of variation was 2.1 ± 0.8 for glucose and 0.14 ± 0.03 for the D-βHb ketone ester; P = 0.04), which remained at their peak for at least 90 min postbolus. Thus, to ensure peak concentrations in the brain for both glucose and ketones, for the bolus experiment we acquired 10 min resting-state scans starting 30 min postbolus.

Current work, using 7T MRS, aims to identify the neural mechanisms by which changes in fuel metabolism affect whole brain connectivity, by testing the impact of energy bioavailability on the production of various metabolites and neurotransmitters.

For more information, see:

Diet modulates brain network stability, a biomarker for brain aging, in young adults. Mujica-Parodi LR, Anar Amgalan, Syed Fahad Sultan, Antal B, Sun X, Skiena S, Lithen A, Adra N, Ratai EM, Weistuch C, Govindarajan ST, Strey HH, Dill KA, Stufflebeam SM, Veech RL, Clarke K. Proc. Natl. Acad.Sci. 117 (11) 6170-6177 (2020); DOI: 10.1073/pnas.1913042117. PDF

Supplementary Material Figure 2: Brain glucose and bHB pharmacokinetic timecourse, as measured with 1H Magnetic Resonance Spectroscopy. Average D-b-hydroxybutyrate (bHB /Cr+PCr) and glucose levels (Glc/Cr+PCr) in the brain (voxel centered on anterior cingulate gyrus) peak around 30 minutes following a ketone or glucose bolus, and continue at peak for at least 90 minutes post-bolus. The increased volatility of glucose (as compared to ketones) in the brain is clearly visible, and suggests that scans comparing the two fuels should occur between 30-40 minutes post-bolus, as per our study design.