Burkhard Mädler | PubMed Health

PubMed2007

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 (94x70x15 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 with 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 patients 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.

Adolescent↗

PubMed2006

Insights into brain microstructure from the T2 distribution.

T2 weighting is particularly sensitive, but notoriously unspecific, to a wide range of brain pathologies. However, careful measurement and analysis of the T2 decay curve from brain tissue promise to provide much improved pathological specificity. In vivo T2 measurement requires accurate 180 pulses and appropriate manipulation of stimulated echoes; the most common approach is to acquire multiple echoes from a single slice. The T2 distribution, a plot of component amplitude as a function of T2, can be estimated using an algorithm capable of fitting a multi-exponential T2 decay with no a priori assumptions about the number of exponential components. T2 distributions from normal brain show peaks from myelin water, intra/extracellular water and cerebral spinal fluid; they can be used to provide estimates of total water content (total area under the T2 distribution) and myelin water fraction (MWF, fractional area under the myelin water peak), a measure believed to be related to myelin content. Experiments on bovine brain suggest that magnetization exchange between water pools plays a minor role in the T2 distribution. Different white matter structures have different MWFs. In normal white matter (NWM), MWF is not correlated with the magnetization transfer ratio (MTR) or the diffusion tensor fractional anisotropy (FA); hence it provides unique information about brain microstructure. Normal-appearing white matter (NAWM) in multiple sclerosis (MS) brain possesses a higher water content and lower MWF than controls, consistent with histopathological findings. Multiple sclerosis lesions demonstrate great heterogeneity in MWF, presumably due to varying myelin contents of these focal regions of pathology. Subjects with schizophrenia were found to have significantly reduced MWF in the minor forceps and genu of the corpus callosum when compared to controls, suggesting that reduced frontal lobe myelination plays a role in schizophrenia. In normal controls, frontal lobe myelination was positively correlated with both age and education; this result was not observed in subjects with schizophrenia. A strong correlation between MWF and the optical density from the luxol fast blue histological stain for myelin was observed in formalin-fixed brain, supporting the use of the MWF as an in vivo myelin marker.

Animals↗