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 observed in untreated subjects with phenylketonuria (PKU). A method to measure cerebral concentrations of phenylalanine (Phe) in vivo would greatly 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 performed using a 2.1-Tesla Bruker Biospec spectrometer. Plasma Phe was measured at the time of the spectroscopic examination in the PKU patients. A Phe signal was observed in all 12 studies performed on the group with PKU, and in five studies cerebral Phe concentrations were measured to be 480 to 780 mumol/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 Phe concentrations can be measured noninvasively using proton nuclear magnetic resonance spectroscopy. A simultaneous measure of Phe and several other cerebral metabolites is obtained with this innovative technology. Adaptations of this technique can be used to investigate PKU and other neurometabolic disorders with modifications of current clinical magnetic resonance imaging systems.