Deuterium MR with a glucose-transporter-1 deficiency syndrome mouse model: ketogenic diet-modulated brain energy metabolism

Motivation: The ketogenic diet is a first-line clinical treatment for glucose-transporter-1 deficiency syndrome (GLUT1-DS). Goal(s): To examine brain energy metabolism in a mouse model of GLUT1-DS by applying deuterium metabolic imaging (DMI) to mice fed either a normal diet (ND) or ketogenic diet (KD). Approach: Following administration of [6,6-2H2]glucose (Glc) or [3,4,4,4-2H4]β-hydroxybutyrate (βHB), employ DMI to evaluate GLUT1-DS mice and wild-type (WT) littermates on ND or KD. Results: The KD results in significant changes in levels of substrates Glc and βHB, and downstream metabolites, compared to the ND. Impact: DMI is directly clinically translatable. These results suggest it holds promise for quantification of the metabolic changes in GLUT1-DS patients, thereby relating these changes to the underlying pathophysiology, clinical symptoms and treatment efficacy in individual patients.