Noninvasive detection of Phenylalanine in the human brain with MRS at 7T

We set out to measure phenylalanine in the human brain using magnetic resonance spectroscopy (MRS) in a ultra-high field 7T MRI scanner. Phenylalanine is a precursor to Norepinephrine, a neurotransmitter important for attention and arousal. Depletion in norepinephrine, especially in the locus coeruleus, has been implicated as an etiological factor in Alzheimer’s disease. Therefore, being able to noninvasively measure phenylalanine in vivo in humans has a multitude of translational applications. Using phantom experiments, we first validate and optimize the MRS techniques used for observing phenylalanine in the brain at 7T. However, we failed to detect phenylalanine in human volunteers (N=15). In order to understand the reasons for this failure, we performed experiments in a cat model with external phenylalanine injections to determine the amount of phenylalanine required for it to be detected in vivo in the brain. This threshold was found to be 3.4 mM. This indicated that phenylalanine concentrations in both healthy and AD patients, that too in a small region such as the locus coeruleus, will likely not meet this threshold. Therefore, we conclude that even with state-of-the-art technologies and 7T MRI, it is not possible to detect phenylalanine in the human brain in vivo under natural conditions.