Abnormally High Levels of Brain N-Acetylaspartate in Children with Sickle Cell Disease

Abstract

BACKGROUND AND PURPOSE: The most abundant metabolite visible by proton magnetic resonance spectroscopy (MRS) in human brain is N-acetylaspartate (NAA), which is often used as a marker of viable neurons. NAA is anecdotally reported to be elevated in children with sickle cell disease (SCD), even though patients can have brain injury or atrophy. We measured NAA levels rigorously in SCD patients to test the hypothesis that NAA is elevated in this patient population.

METHODS: We evaluated 26 children with SCD and 25 age-similar healthy control subjects using a double spin-echo MRS technique to interrogate a 16 cc volume of interest in the basal ganglia. We acquired MRS spectra with an echo time (TE) of 30 ms to evaluate lipids, and with TE = 144 to show abundant metabolites against a flat baseline. We characterized metabolite relaxation properties and measured the water peak as an internal standard, to calculate the absolute quantity of metabolites.

RESULTS: The ratio of NAA:Choline was significantly elevated in basal ganglia of patients at both echo times (P <.016), and the absolute quantity of NAA was also elevated, with [NAA] 7–12% higher in patients than in control subjects. The measured increase in [NAA] cannot be explained by metabolite relaxation properties or by differences in tissue water content.

CONCLUSION: Brain NAA is greater in children with SCD than in healthy control subjects and appears not to be a reliable marker of viable neurons in SCD patients.