New Techniques in the Study of the Brain Development in Newborn

In the last few decades, the survival rates of preterm babies and full-term babies with severe diseases have increased due to advances in perinatal care. Understandably however, higher survival rates have not been accompanied by an overall reduction of morbidity, so that limitation of long-term neurodevelopmental abnormalities remains a major challenge of early care (Plaisier et al., 2014). The possibility to better predict the outcome of newborns at neurodevelopmental risk is essential to inform early intervention, to allow best allocation of resources, and to minimize long-term consequences. Unfortunately, clinicians continue to possess limited ability to predict neurodevelopmental outcomes, mainly relying, in most settings, on early findings at cranial ultrasound (cUS). Recent studies (Smyser et al., 2012) have proven the power of magnetic resonance imaging (MRI) superior to other neuroimaging modalities, including cUS, in detecting cerebral injury. Neonatal MRI provides non-invasive, highresolution images in less than 1 h; scans are performed without sedation eliminating the risk and the costs associated to it and are not associated to radiation exposure, as for computerized tomography (CT). The application of MRI in the neonatal population is rapidly increasing, making MRI one of the key diagnostic tools for the assessment of early brain development and injury. In specific clinical groups, such as for example very preterm infants, cerebral MRI should become part of standard clinical care and should be systematically performed at term equivalent age (TEA). Accurate assessment of cortical folding at TEA provides an important marker for structural brain growth and maturation. Myelination of the posterior limb of the internal capsule (PLIC) at around 36– 38 weeks gestation, identifiable on T1 but also on T2-weighted images, is another important maturational hallmark, since its presence and symmetry are very powerful in predicting motor outcome. MR imaging is superior to cUS also in detecting diffuse white matter (WM) injury. Indeed, although cystic periventricular leukomalacia is seen less often, diffuse non-cystic types of WM injury, including punctate WM lesions and diffuse excessive high signal intensity, are most frequent and are considered the leading cause of disturbed brain growth, connectivity, and functionality. The predictive power of conventional MRI in this domain remains relatively low, as it is not sensitive enough to analyze changes in microstructure; however, it is greatly enhanced by the use of advanced MR techniques targeting the WM, such as diffusion tensor imaging (DTI), that can help analyzing brain growth in extremely preterm babies in the absence of evident WM abnormalities (Ramenghi et al., 2009). Diffusion tensor imaging (DTI) is a relatively new MR modality that assesses water diffusion in biological tissues at microstructural level. The diffusion tensor describes an ellipsoid in space characterized by the diffusion eigenvalues (λ1,λ2,λ3) in the three orthogonal directions and their corresponding eigenvectors. In brain WM, axial diffusivity (λ1) is oriented along the direction of the main tracts and radial diffusivity (λ2 and λ3) is oriented perpendicular to these tracts. Average diffusivity (Dav) reflects the mean of these eigenvalues and it is an indicator of brain maturation and/or injury. Dav decreases with increasing age probably for decreasing water content and increasing complexity of WM structures with myelination. Fractional anisotropy (FA) reflects the variance of the eigenvalues, ranging from 0 (isotropic diffusion) to 1 (anisotropic). The diffusion is mainly anisotropic because the water molecules preferentially move in the direction of fascicles of axons (Adams et al., 2010). In the white and gray matter, there is similar water content but different Dav value probably because the WM is less restrictive to water motion. Brain water content decreases with increasing gestational age and this mostly increases the WM anisotropy values. This increase has also been attributed to changes in WM structure associated with histologic maturation, and it takes place at different rates in different brain areas [the main areas analyzed are in commissural tracts, the corpus callosum (CC), and in projection tracts, the corticospinal tracts (CSTs)]. Developmental changes in anisotropy of cerebral cortex reflect changes in its microstructure, such as the arborization of basal dendrites of cortical neurons, the innervation of the cortical plate by thalamocortical and cortico-cortical fibers, all processes which are important basis of later functional connectivity (Huppi and Dubois, 2006). Because there are strongly preferred directions of diffusion, it is possible to create color maps of neonatal brain with diffusion tensor post-processing techniques. The color maps are based on major orientation with red representing right– left, green representing antero–posterior, and blue representing superior–inferior anatomical directions (De Bruïne et al., 2013) (Figure 1).