Abstract #0612

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

Mansimran Virk¹, Razi Kitaneh², Marcella M. Mignosa², Scott McIntyre³, Terence W. Nixon³, Kelly S. DeMartini⁴, Stephanie O’Malley⁴, John H. Krystal⁴, Henk M. De Feyter³, Gustavo A. Angarita², Graeme M. Mason³, Robin A. de Graaf³, and Chathura Kumaragamage⁵

¹Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ²Department of Psychiatry, Clinical Neuroscience Research Unit (CNRU), Yale University School of Medicine, New Haven, CT, United States, ³Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, CT, United States, ⁴Department of Psychiatry, Center for the Translational Neuroscience in Alcohol (CTNA), Yale University School of Medicine, New Haven, CT, United States, ⁵Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

Synopsis

Keywords: Psychiatric Disorders, Brain, Spectroscopy, Metabolism, Alcohol Use Disorder (AUD)

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.

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