IN-VIVO MEASUREMENT OF PHENYLALANINE IN HUMAN BRAIN BY PROTON NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

Disorders of the CNS are the major causes of morbidity and mortality o bserved in untreated subjects with phenylketonuria (PKU). A method to measure cerebral concentrations of phenylalanine (Phe) in vivo would g reatly enhance the ability to investigate both the pathophysiology and the efficacy of therapy of this aminoacidopathy. Twelve image-guided localized proton nuclear magnetic resonance spectroscopic studies were performed in seven subjects with PKU using pulse sequences optimized to detect the aromatic protons of Phe. Ten control studies were also p erformed using a 2.1-Tesla Bruker Biospec spectrometer. Plasma Phe was measured at the time of the spectroscopic examination in the PKU pati ents. A Phe signal was observed in all 12 studies performed on the gro up with PKU, and in five studies cerebral Phe concentrations were meas ured to be 480 to 780 mu mol/g. Plasma Phe concentrations were 0.7 to 3.3 mM (10.8 to 54.8 mg/dL) in the subjects with PKU. Human cerebral P he concentrations can be measured noninvasively using proton nuclear m agnetic resonance spectroscopy. A simultaneous measure of Phe and seve ral other cerebral metabolites is obtained with this innovative techno logy. Adaptations of this technique can be used to investigate PKU and other neurometabolic disorders with modification of current clinical magnetic resonance imaging systems.