Characterization of white matter alterations in phenylketonuria by magnetic resonance relaxometry and diffusion tensor imaging

A multimodal MR study including relaxometry, diffusion tensor imaging (DTI), and MR spectroscopy was performed on patients with classical phenylketonuria (PKU) and matched controls, to improve our understanding of white matter (WM) lesions. Relaxometry yields information on myelin loss or malformation and may substantiate results from DTI attributed to myelin changes. Relaxometry was used to determine four brain compartments in normal-appearing brain tissue (NABT) and in lesions: water in myelin bilayers (myelin water, MW), water in gray matter (GM), water in WM, and water with long relaxation times (cerebrospinal fluid [CSF]-like signals). DTI yielded apparent diffusion coefficients (ADCs) and fractional anisotropies. MW and WM content were reduced in NABT and in lesions of PKU patients, while CSF-like signals were significantly increased. ADC values were reduced in PKU lesions, but also in the corpus callosum. Diffusion anisotropy was reduced in lesions because of a stronger decrease in the longitudinal than in the transverse diffusion. WM content and CSF-like components in lesions correlated with anisotropy and ADC. ADC values in lesions and in the corpus callosum correlated negatively with blood and brain phenylalanine (Phe) concentrations. Intramyelinic edema combined with vacuolization is a likely cause of the WM alterations. Correlations between diffusivity and Phe concentrations confirm vulnerability of WM to high Phe concentrations.

Differentiating hippocampal subregions by means of quantitative magnetization transfer and relaxometry: preliminary results

The hippocampal formation (HF) of healthy control subjects and schizophrenic patients was examined using an MRI experiment that implements sequences for relaxometry and magnetization transfer (MT) quantification. In addition to the semi-quantitative magnetization transfer ratio (MTR), all of the observable properties of the binary spin bath model were included. The study demonstrates that, in contrast to the MTR, quantitative MT parameters (especially the T2 relaxation time of restricted protons, T2b) are capable to differentiate functionally significant subregions within the HF. The MT methodology appears to be a promising new tool for the differential microstructural evaluation of the HF in neuropsychiatric disorders accompanied by memory disturbances.

Novel magnetic iron oxide nanoparticles coated with poly(ethylene imine)-g-poly(ethylene glycol) for potential biomedical application: synthesis, stability, cytotoxicity and MR imaging

Magnetic iron oxide nanoparticles have found application as contrast agents for magnetic resonance imaging (MRI) and as switchable drug delivery vehicles. Their stabilization as colloidal carriers remains a challenge. The potential of poly(ethylene imine)-g-poly(ethylene glycol) (PEGPEI) as stabilizer for iron oxide (γ-Fe₂O₃) nanoparticles was studied in comparison to branched poly(ethylene imine) (PEI). Carrier systems consisting of γ-Fe₂O₃-PEI and γ-Fe₂O₃-PEGPEI were prepared and characterized regarding their physicochemical properties including magnetic resonance relaxometry. Colloidal stability of the formulations was tested in several media and cytotoxic effects in adenocarcinomic epithelial cells were investigated. Synthesized γ-Fe₂O₃ cores showed superparamagnetism and high degree of crystallinity. Diameters of polymer-coated nanoparticles γ-Fe₂O₃-PEI and γ-Fe₂O₃-PEGPEI were found to be 38.7 ± 1.0 nm and 40.4 ± 1.6 nm, respectively. No aggregation tendency was observable for γ-Fe₂O₃-PEGPEI over 12 h even in high ionic strength media. Furthermore, IC₅₀ values were significantly increased by more than 10-fold when compared to γ-Fe₂O₃-PEI. Formulations exhibited r₂ relaxivities of high numerical value, namely around 160 mM⁻¹ s⁻¹. In summary, novel carrier systems composed of γ-Fe₂O₃-PEGPEI meet key quality requirements rendering them promising for biomedical applications, e.g. as MRI contrast agents.

Myelination of the right parahippocampal cingulum is associated with physical activity in young healthy adults.

Recent evidence suggests that individual differences in physical activity (PA) may be associated with individual differences in white matter microstructure and with grey matter volume of the hippocampus. Therefore, this study investigated the association between PA and white matter microstructure of pathways connecting to the hippocampus. A total of 33 young, healthy adults underwent magnetic resonance imaging (MRI). High angular resolution diffusion-weighted imaging and multi-component relaxometry MRI scans (multi-component driven equilibrium pulse observation of T1 and T2) were acquired for each participant. Activity levels (AL) of participants were calculated from 72-h actigraphy recordings. Tractography using the damped Richardson Lucy algorithm was used to reconstruct the fornix and bilateral parahippocampal cinguli (PHC). The mean fractional anisotropy (FA) and the myelin water fraction (MWF), a putative marker of myelination, were determined for each pathway. A positive correlation between both AL and FA and between AL and MWF were hypothesized for the three pathways. There was a selective positive correlation between AL and MWF in the right PHC (r = 0.482, p = 0.007). Thus, our results provide initial in vivo evidence for an association between myelination of the right PHC and PA in young healthy adults. Our results suggest that MWF may not only be more specific, but also more sensitive than FA to detect white matter microstructural alterations. If PA was to induce structural plasticity of the right PHC this may contribute to reverse structural alterations of the right PHC in neuropsychiatric disorder with hippocampal pathologies.