Phenylketonuria: white-matter changes assessed by 3.0-T magnetic resonance (MR) imaging, MR spectroscopy and MR diffusion

This study evaluated the sensitivity of a 3.0-Tesla (T) magnetic resonance imaging (MRI) in measuring cerebral phenylalanine using proton magnetic resonance spectroscopy and in assessing MR-documented white-matter changes by means of diffusion studies (diffusion-weighted imaging, apparent diffusion coefficient map; diffusion tensor imaging) in patients with phenylketonuria. Thirty-two patients with the classical clinical and biochemical deficits of phenylketonuria underwent biochemical (blood phenylalanine), genotypic (phenylalanine hydroxylase gene) and radiological investigation by means of MRI, proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging with a 3.0-T scanner. Periventricular and subcortical white-matter changes were detected on all MR scans. In 29/32 patients, proton magnetic resonance spectroscopy easily documented abnormal signal elevation at 7.36 ppm, corresponding to phenylalanine, despite its low concentration. Phenylalanine signal amplitude relative to the creatine/phosphocreatine signal increased linearly with blood phenylalanine values (r 0.7067; p < 0.001). Diffusion MRI demonstrated hyperintensity in the areas exhibiting MRI changes as well as decreased apparent diffusion coefficient values, but fractional anisotropy indices were normal. The high signal, together with better spectral, spatial, contrast and temporal resolution, makes the 3.0-T MR the most suitable technique in the study of the phenylketonuria. In particular, the multimodal approach with MRI, proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging can provide more information than previous studies performed with low-field systems.