Metabolism in the human brain following oral consumption of a keto-ester for applications in alcohol use disorder (AUD) with 1H-MRSI

Motivation: Oral consumption of the ketone-monoester (R)−3-hydroxybutyl-(R)−3-hydroxybutyrate (HBHB) raises the plasma ketone-body β-hydroxybutyrate (BHB), providing a means to study ketone body metabolism. HBHB Hydrolysis however produces BHB and 1,3-butanediol, which share prominent spectral signatures complicating metabolite quantification. Goal(s): Investigate feasibility and robustly detection of BHB. Subsequently, investigate brain ketone-body metabolism in alcohol use disorder (AUD). Approach: HBHB was administered orally, and brain metabolism was monitored over 90 minutes using MRS with 1,3-butanediol included as a reference spectrum. Results: Combined BHB and the co-edited 1,3-butanediol were robustly detected, though separate quantification of BHB and 1,3-butanediol was challenging due to low concentrations. Impact: Accurate BHB quantification is critical to evaluate BHB transport into the brain post-keto-ester consumption. A modified J-difference editing strategy is expected to mitigate shortcomings to investigate BHB transport to assess disease severity and gain insights related to craving in AUD.