In-Vivo NMR Spectroscopy in Patients with Phenylketonuria: Changes of Cerebral Phenylalanine Levels Under Dietary Treatment

Abstract

Localized proton magnetic resonance spectroscopy at short echo times was used to measure phenylalanine (Phe) in parieto-occipital periventricular brain. Six treated adult patients with phenylketonuria were investigated repeatedly following reinstitution of a Pherestricted diet. Difference spectroscopy clearly enabled the identification of elevated cerebral Phe levels by subtracting spectra obtained from healthy volunteers. Estimates of absolute brain concentrations always yielded values well below the serum levels with ratios [Phe]_brain/[Phe]_serum ranging from 0.27 to 0.63. A plot of [Phe]_brain versus [Phe]_semm could be fitted to a straight line (R = 0.90) if [Phe]_serum was below 1.3 mM. Measurements at higher serum levels could only be performed in one patient and yielded brain Phe concentrations of 0.63 ± 0.10 mM suggesting a saturation of the carrier systems. The feasibility to quantify Phe transport across the. blood-brain barrier in humans non-invasively employing in-vivo proton spectroscopy can effectively improve the prognostic significance of serum data.

Key words

Blood-brain barrier transport - Cerebral phenylalanine - Proton magnetic resonance spectroscopy -Phenylketonuria - Transport kinetics