Insights from in vitro fetal magnetic resonance imaging of cerebral development

The development of the cerebral cortex, white matter microstructure, and the basal ganglia can be well characterized using structural magnetic resonance imaging (MRI). In this review, we analyzed structural in vitro MRI studies of transient cellular cerebral zones that are sites of neurogenetic events (proliferation, migration, cell aggregation, growth of axonal pathways, myelinization, and synaptogenesis). During early fetal life, from 9-13 postconceptional weeks, a thick, densely packed cellular ventricular/subventricular zone and ganglionic eminence indicate intensive proliferation of neuroepithelial stem cells. During the mid and late fetal phase, other cellular zones also became discernable: (1) the intermediate zone as a migratory and axonal growth zone; (2) the subplate zone as a synaptic, extracellular matrix-rich "waiting" compartment; and (3) the cell-dense cortical plate with postmigratory neurons. The preterm phase is characterized by the growth of cortical, thalamic, and striatal pathways; formation of white matter segments; and stratification within the subplate. Thalamocortical fibers cause lamination in the cortical plate, which leads to the formation of a substrate of sensory input. Preterm cerebral immaturity is characterized by considerable extracellular space at sites of axonal growth and a delineable subplate. The intensity of axonal growth, together with a high, gradient-dependent requirement for axonal guidance, forms a substrate for selective vulnerability of specific segments of cerebral white matter in the preterm brain. In summary, the combination of in vitro MRI, histologic analysis, and in vivo MRI is a promising new approach for studying the etiology and treatment of developmental disorders.