Normal-appearing white matter in patients with phenylketonuria: Water content, myelin water fraction, and metabolite concentrations

Purpose: To prospectively assess relative water content (RWC), myelin water fraction (MWF), and hydrogen 1 magnetic resonance (MR) spectroscopy findings in the white matter (WM) of patients with phenylketonuria (PKU). Materials and Methods: This study was approved by the institution's investigational review board, and informed consent was obtained. T2 water relaxation data were acquired by using a 48-echo measurement, in a transverse plane through the genu and splenium of the corpus callosum in 16 patients (six men, 10 women; age range, 18-40 years) with PKU and 16 age- and sex-matched Control subjects. MR spectroscopy was performed in a voxel (94 X 70 X 15 mm) above the ventricles. WM in control subjects (defined as normal WM) was Compared with normal-appearing WM (NAWM) and diffuse WM lesions in patients with PKU by using a Student t test. Results: Patients wit It PKU had two forms of NAWM: (a) areas that. looked normal on intermediate-weighted (IW) and T2-weighted MR images and long T2 maps and (b) areas that, looked normal on IW and T2-weighted MR images but were hyperintense on long T2 maps. Both forms of NAWM showed increased RWC (up to 2.5%, P < .001) and reduced MWF (up to 56%, P < .001) relative to normal WM; these changes paralleled those seen in diffuse WM lesions. Approximately 9% of the water in diffuse WM lesions was in a reservoir with a long T2 time of 200-800 msec. Myoinositol concentrations were reduced by 14% (P = .003) in patient's with PKU. Conclusion: In patients with PKU, NAWM and diffuse WM lesions have altered RWC and MWF relative to normal WM, and diffuse WM lesions show a redistribution of water into an extracellular reservoir with a long T2 time.