Striking evidence from a number of disciplines has focused attention on the interplay between the developing organism and the circumstances in which it finds itself. The organism can express specific adaptive responses to its environment which include short term changes in physiology as well as long-term adjustments. Early life events may therefore affect any organ including the brain. With the progress in reproductive medicine and neonatal intensive care, we are confronted with an increasing number of newborns at high risk for modification of early brain development. Advanced Magnetic Resonance Imaging (MRI) techniques have recently provided us with new data on fine structural alteration of the brain in these high risk newborns. Volumetric analysis of 3D-MR imaging data sets are achieved by segmentation of the imaged volume into the different tissue types with 3-dimensional renderings. Applying these techniques to the study of the high risk newborn new insights into the modification of cortical development have been gained (2). Preterm infants exposed to postnatal corticosteroid treatment for chronic lung disease were found to have a 30% reduction in cortical gray matter development (3). A similar reduction in cortical development was found in preterm infants after intrauterine growth restriction (IUGR)(5). The hippocampus is known for its crucial role in cognitive function such as memory and learning. It is sensitive to hypoxia, and to stress hormones. The total volume of both hippocampal formations was found to be significantly smaller in IUGR preterm infants than in the control group. These modifications of cortical development were also found in preterm infants studied at 8 years and were correlated with neurofunctional deficits (4). Diffusion weighted imaging further allows assessment of microstructural development of the white matter structures (1). Factors influencing diffusion in the developing brain are related to anisotropy, which describes the preferential direction of water diffusivity. The geometric nature of the diffusion tensor can be used to display the fiber architecture of the brain white matter and its alteration due to modification of brain development. IUGR preterm infants showed microstructural alterations in major associative white matter tracts. To assess brain functioning early on, measurement tools of neurobehavioral functioning have been developed. The Assessment of preterm infant behaviour (APIB) as a newborn behavioral assessment methodology provides an integrated subsystem profile of the infant’s current ability to process environmental input and assesses the level of brain functioning. Significant correlation of behavioral maturation and cortical brain development has be shown using APIB to assess brain function in newborns. Advanced MR-techniques such as 3D-MRI , diffusion tensor imaging combined with specific neurobehavioral testing allow us to study normal brain development in the newborn and assess effects of endogenous or exogenous insults with implications for longterm neuropsychological development.