β-Hydroxybutyrate Detection with Proton MR Spectroscopy in Children with Drug-Resistant Epilepsy on the Ketogenic Diet

• Published in: American journal of neuroradiology : AJNR 2018-07, Vol.39 (7), p.1336-1340
• Main Authors: Wright, J N, Saneto, R P, Friedman, S D
• Format: Article
• Language: English
• Subjects: Amino acids; Blood levels; Brain; Children; Choline; Correlation analysis; Correlation coefficients; Creatine; Diet; Drug resistance; Epilepsy; High fat diet; Ketogenesis; Lactic acid; Low carbohydrate diet; Magnetic resonance spectroscopy; Mathematical analysis; N-Acetylaspartate; Patients; Pediatrics; Spectroscopy; Spectrum analysis
• ISSN: 0195-6108; 1936-959X
• DOI: 10.3174/ajnr.A5648

The ketogenic diet, including both classic and modified forms, is an alternative to antiepileptic medications used in the treatment of drug-resistant epilepsy. We sought to evaluate the utility of proton MR spectroscopy for the detection of β-hydroxybutyrate in a cohort of children with epilepsy treated with the ketogenic diet and to correlate brain parenchymal metabolite ratios obtained from spectroscopy with β-hydroxybutyrate serum concentrations. Twenty-three spectroscopic datasets acquired at a TE of 288 ms in children on the ketogenic diet were analyzed with LCModel using a modified basis set that included a simulated β-hydroxybutyrate resonance. Brain parenchymal metabolite ratios were calculated. Metabolite ratios were compared with serum β-hydroxybutyrate concentrations, and partial correlation coefficients were calculated using patient age as a covariate. β-hydroxybutyrate blood levels were highly correlated to brain β-hydroxybutyrate levels, referenced as either choline, creatine, or -acetylaspartate. They were inversely but more weakly associated with -acetylaspartate, regardless of the ratio denominator. No strong concordance with lactate was demonstrated. Clinical MR spectroscopy in pediatric patients on the ketogenic diet demonstrated measurable β-hydroxybutyrate, with a strong correlation to β-hydroxybutyrate blood levels. These findings may serve as an effective tool for noninvasive monitoring of ketosis in this population. An inverse correlation between serum β-hydroxybutyrate levels and brain tissue -acetylaspartate suggests that altered amino acid handling contributes to the antiepileptogenic effect of the ketogenic diet.