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1H-Magnetic Resonance Spectroscopy of Cerebral Phenylalanine Content and its Transport at the Blood-Brain Barrier

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Neural Metabolism In Vivo

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 4))

Abstract

Proton magnetic resonance spectroscopy (1H-MRS) has been used in multiple studies to quantify the cerebral phenylalanine (Phe) content in humans, mostly phenylketonuria (PKU) patients. PKU has also been extensively studied by magnetic resonance imaging (MRI). The major published findings about MRS and MRI in PKU are summarized. With different MRI techniques, the characteristic white matter lesions in PKU patients have been characterized, providing a picture that is in agreement with partly reversable dysmyelination, possibly in the form of spongiform alterations. The 1H-MRS results from studies of PKU patients are summarized in a metaanalysis where major factors for differences between the published studies are identified and essential methodologic specifics needed for the determination of Phe concentrations are given. It was found that the steady state blood/brain Phe concentration ratio seems to be fairly stable for the large majority of PKU patients, leaving little room for individual dietary treatment, based on potential individual sensitivity to dietary Phe. Furthermore, 1H-MRS has been used to investigate the dynamics of cerebral Phe uptake in humans with and without PKU. The theoretical background for the description of the blood-brain-barrier (BBB) dynamics is given and the main results from these studies described, among them the documentation of a BBB blockade for Phe inflow by oral supplementation with large neutral amino acids.

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Notes

  1. 1.

    Data from the Münster Group (Möller et al. 1997) was first combined and then divided into two cohorts: data from the early papers (Möller et al. 1997; Moller et al. 1998) in one cohort, the newer data from a more recent publication (Weglage et al. 2001b) which seem to have been obtained with somewhat different methodology (Pietz et al. 2002) into another.

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Acknowledgement

Many thanks to my collaborators, including Dr. Jean-Marc Nuoffer and in particular Dr. Joachim Pietz, without whose long-standing efforts and interest in improving our understanding of PKU our research would not have been possible. Support by the Swiss National Science Foundation is also gratefully acknowledged (3100A0-103938, 320000-120324).

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  1. Department of Clinical Research, University Bern, AMSM, DRNN/DKF, Pavilion 52, Inselspital, 35, CH-3010, Bern, Switzerland

    Roland Kreis Ph.D.

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Correspondence to Roland Kreis Ph.D. .

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  1. School of Medicine, Hoglund Brain Imaging Center, University of Kansas, Rainbow Blvd. 3901, Kansas City, 66160, Kansas, USA

    In-Young Choi

  2. Inst. Physique de la Matière Complexe, Labo. d'Imagerie Fonctionnelle et, Ecole Polytechnique Fédérale de Lausanne, Lausanne, 1015, Switzerland

    Rolf Gruetter

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Kreis, R. (2012). 1H-Magnetic Resonance Spectroscopy of Cerebral Phenylalanine Content and its Transport at the Blood-Brain Barrier. In: Choi, IY., Gruetter, R. (eds) Neural Metabolism In Vivo. Advances in Neurobiology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1788-0_40

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