Imaging the developing brain

In recent years, the repertoire of magnetic resonance imaging (MRI) has dramatically increased, leading to greatly improved assessment of the stages of development of the brain during gestation and early infancy. Besides the traditional radiological scans, which provide images showing contrast based on tissue variations of proton density, and the relaxations times T1 and T2, measurements of water mobility are routinely made using diffusion-weighted imaging. The current Special Issue brings together seven cutting-edge papers which shed light non-invasively on the morphogenetic processes taking place in development, and thus promote understanding in developmental systems neuroscience, an area in which MRI reigns supreme due to its very low invasiveness. The first article, by Colin Studholme and co-authors, reviews current MRI research on living fetal brain, with the aim of improving the interfaces between microscopic and macroscopic approaches. New approaches to the challenge of automated labelling of tissue zones within fetal brain MRI data are described. These provide the basis for later work that has created the first maps of tissue growth rate and cortical folding in normally developing brains in-utero, and thus provide valuable findings that complement those derived from post-mortem anatomy. Additionally these allow larger population studies of the influence of maternal environmental and genetic influences on early brain development. This review is followed by a review by Hao Huang and coauthors, focusing specifically on the use of diffusion weighted MRI, and the comparison of MRI findings with ex-vivo histology. Diffusion tensor imaging (DTI) and histology are complementary tools which can delineate the fetal brain structures at both macroscopic and microscopic level. Major components of the fetal brain, including the cortical plate, fetal white matter and the cerebral wall layer between the ventricle and subplate, were investigated using DTI and histology. Anisotropic metrics derived from DTI were used to quantify the microstructural changes during the dynamic process of human fetal cortical development and prenatal development of other animal models. Fetal white matter pathways were traced with DTI-based tractography to reveal growth patterns of individual white matter tracts and corticocortical connectivity. These detailed anatomical accounts of the structural changes during the fetal period may help to detect developmental and cognitive brain disorders at their early stages. Further quantitative details of fetal development are provided by Linlin Yang and co-authors. Using 3.0 T MRI, they investigated the development of the fetal cerebral lobes between 20 and 28 weeks gestational age. Thirty-six fetal cadaver brains were studied. Many lobular parameters were measured, including the parenchyma thickness of the fronto-parietal and the temporal lobes, the margin length of the fronto-parietal lobes, and the dimensions of the insula, the temporal lobes, the Sylvian fissure and the hippocampus. They concluded that the fetal cerebrum lobes develop asynchronously during this period, and that 24 weeks gestational age could be a turning point for the development pattern to change from primitive to mature. This article is followed by a closely related study by Kenichi Oishi and co-authors, which focuses on the development of an automated structure parcellation method, customized for the neonatal and pediatric population. Such a method fulfills the vital need to avoid interand intra-reader variability regarding anatomical boundary definitions, and can hence increase the precision of quantitative measurements. The development of the brain is structure-specific, and the growth rate of each structure differs depending on the age of the subject. Currently, most clinical MRIs are evaluated qualitatively to assist in clinical decision-making and diagnosis. The clinical MRI report usually does not provide quantitative values that can be used to monitor developmental status. The next contribution, by Emily Dennis and co-authors, reviews a representative selection of recent MRI findings on brain connectivity in autism, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Turner syndrome, and ADHD. Major strides have been made in understanding the developmental trajectory of the human connectome, offering insight into characteristic features of brain development and biological processes involved in developmental brain disorders. They also discuss some common themes, including hemispheric specialization – or asymmetry – and sex differences, and conclude by discussing some promising future directions in connectomics, including the merger of imaging and genetics, and a deeper investigation of the relationships between structural and functional connectivity. This article is followed by a research paper by Marcel Moran and co-authors, addressing specifically the abnormal development of the insular cortex, which is coming to be regarded as playing a crucial role in childhood-onset schizophrenia. Their finding that the volume of the right insula negatively correlates with positive symptoms of schizophrenia will help in differential diagnosis and in better understanding of the neural correlates of this severe disease. It may also throw light on issues of the sense of self in healthy human subjects. The final article in this Special Issue, by Xiaodong Zhang and coworkers, deals not with human brain development, but with a very