Cerebral White Matter Maturation Patterns in Preterm Infants: An MRI T2 Relaxation Anisotropy and Diffusion Tensor Imaging Study

BACKGROUND AND PURPOSE

Preterm birth is associated with worse neurodevelopmental outcome, but brain maturation in preterm infants is poorly characterized with standard methods. We evaluated white matter (WM) of infant brains at term‐equivalent age, as a function of gestational age at birth, using multimodal magnetic resonance imaging (MRI).

METHODS

Infants born very preterm (<32 weeks gestation) and late preterm (33‐36 weeks gestation) were scanned at 3 T at term‐equivalent age using diffusion tensor imaging (DTI) and T2 relaxometry. MRI data were analyzed using tract‐based spatial statistics, and anisotropy of T2 relaxation was also determined. Principal component analysis and linear discriminant analysis were applied to seek the variables best distinguishing very preterm and late preterm groups.

RESULTS

Across widespread regions of WM, T2 is longer in very preterm infants than in late preterm ones. These effects are more prevalent in regions of WM that myelinate earlier and faster. Similar effects are obtained from DTI, showing that fractional anisotropy (FA) is lower and radial diffusivity higher in the very preterm group, with a bias toward earlier myelinating regions. Discriminant analysis shows high sensitivity and specificity of combined T2 relaxometry and DTI for the detection of a distinct WM development pathway in very preterm infants. T2 relaxation is anisotropic, depending on the angle between WM fiber and magnetic field, and this effect is modulated by FA.

CONCLUSIONS

Combined T2 relaxometry and DTI characterizes specific patterns of retarded WM maturation, at term equivalent age, in infants born very preterm relative to late preterm.     

In vitro biomedical applications of functionalized iron oxide nanoparticles,including those not related to magnetic properties

Superparamagnetic iron oxide nanoparticles (SPION) are very promising contrast media, especially for molecular imaging, due to their superior NMR efficacy. They even have wider biomedical applications such as in drug and gene delivery, tissue engineering and bioseparation, or as sensitive biological nanosensors. By coupling them to affinity ligands, SPION can bind to drugs, proteins, enzymes, antibodies or nucleotides. For in vitro biomedical applications, the detection of molecular interaction is possible by using a diversity of systems capable of sensing the magnetic properties of these materials. The goal of the present work was to develop and validate various in vitro biomedical applications of ultrasmall superparamagnetic particles of iron oxide (USPIO), including some that are not related to their magnetic properties. USPIO coated with dextran, starch or bisphosphonate exposing carboxylate groups were synthesized and some of them were functionalized by conjugating various biomolecules, such as biotin, streptavidin and apoptosis, or VCAM‐1 specific peptides. The in vitro biomedical applications assessed in the present work included: (1) the relaxometric measurement of antibody concentration, cell receptor expression, molecular interaction, and enzymatic activity in aqueous suspensions; (2) MRI visualization of cells and detection of molecular interaction in an ELISA system; (3) ELISA applications of USPIO derivatives; and (4) detection of specific biomolecules by histochemistry. Our results confirm that rapid and simple in vitro detection of a diversity of functionalized SPION with relevance in medicine is possible by the existing NMR techniques and by chemical staining reactions. The protocols can be applied to minimally prepared biological samples (e.g. whole blood, blood plasma or serum, cell suspensions, biopsies, histological preparations, etc.), and often do not need complicated systems of signal amplification. The use of SPION labeled compounds could furthermore contribute to cost reductions in the diagnosis and in patient care. Copyright © 2010 John Wiley & Sons, Ltd.     

lacZ as a genetic reporter for real‐time MRI

Molecular imaging based on MRI is currently hampered by the lack of genetic reporters for in vivo imaging. We determined that the commercially available substrate S‐Gal? can be used to detect genetically engineered β‐galactosidase expressing cells by MRI. The effect and specificity of the reaction between β‐galactosidase and S‐Gal? on MRI contrast were determined both in vitro and in vivo. β‐galactosidase activity in the presence of S‐Gal? resulted in enhanced T₂ and T*₂ MR‐contrast, which was amplified with increasing magnetic field strengths (4.7‐17.6 T) in phantom studies. Using both lacZ⁺ transgenic animals and lacZ⁺ tissue transplants, we were able to detect labeled cells in live animals in real time. Similar to phantom studies, detection of the labeled cells/tissues in vivo was enhanced at high magnetic fields. These results demonstrate that the genetic reporter, lacZ, can be used as an in vivo marker gene using high‐field‐strength MRI. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.