title: Quantitative and Qualitative Analysis of Transient Fetal Compartments during Prenatal Human Brain Development.
abstract: The cerebral wall of the human fetal brain is composed of transient cellular compartments, which show characteristic spatiotemporal relationships with intensity of major neurogenic events (cell proliferation, migration, axonal growth, dendritic differentiation, synaptogenesis, cell death, and myelination). The aim of the present study was to obtain new quantitative data describing volume, surface area, and thickness of transient compartments in the human fetal cerebrum. Forty-four postmortem fetal brains aged 13-40 postconceptional weeks (PCW) were included in this study. High-resolution T1 weighted MR images were acquired on 19 fetal brain hemispheres. MR images were processed using in-house software (MNI-ACE toolbox). Delineation of fetal compartments was performed semi-automatically by co-registration of MRI with histological sections of the same brains, or with the age-matched brains from Zagreb Neuroembryological Collection. Growth trajectories of transient fetal compartments were reconstructed. The composition of telencephalic wall was quantitatively assessed. Between 13 and 25 PCW, when the intensity of neuronal proliferation decreases drastically, the relative volume of proliferative (ventricular and subventricular) compartments showed pronounced decline. In contrast, synapse- and extracellular matrix-rich subplate compartment continued to grow during the first two trimesters, occupying up to 45% of telencephalon and reaching its maximum volume and thickness around 30 PCW. This developmental maximum coincides with a period of intensive growth of long cortico-cortical fibers, which enter and wait in subplate before approaching the cortical plate. Although we did not find significant age related changes in mean thickness of the cortical plate, the volume, gyrification index, and surface area of the cortical plate continued to exponentially grow during the last phases of prenatal development. This cortical expansion coincides developmentally with the transformation of embryonic cortical columns, dendritic differentiation, and ingrowth of axons. These results provide a quantitative description of transient human fetal brain compartments observable with MRI. Moreover, they will improve understanding of structural-functional relationships during brain development, will enable correlation between in vitro/in vivo imaging and fine structural histological studies, and will serve as a reference for study of perinatal brain injuries.
authors.affiliation: Department of Developmental Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of ZagrebZagreb, Croatia; Division of Development and Growth, Department of Pediatrics, University of GenevaGeneva, Switzerland.
authors.forename: Lana
authors.initials: L
authors.lastname: Vasung
authors.affiliation: Ludmer Centre for Neuroinformatics, McGill Centre for Integrative Neuroscience, Department of Biomedical Engineering, Montreal Neurological Institute, Montreal, McGill University Montreal, QC, Canada.
authors.forename: Claude
authors.initials: C
authors.lastname: Lepage
authors.affiliation: Department of Developmental Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of Zagreb Zagreb, Croatia.
authors.forename: Milan
authors.initials: M
authors.lastname: Radoš
authors.affiliation: Department of Developmental Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of ZagrebZagreb, Croatia; Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of MedicineNew Haven, CT, USA.
authors.forename: Mihovil
authors.initials: M
authors.lastname: Pletikos
authors.affiliation: Ludmer Centre for Neuroinformatics, McGill Centre for Integrative Neuroscience, Department of Biomedical Engineering, Montreal Neurological Institute, Montreal, McGill University Montreal, QC, Canada.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Goldman
authors.affiliation: Laboratory of Neurology and Imaging of Cognition, Department of Neuroscience, University of Geneva Geneva, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Richiardi
authors.affiliation: Department of Developmental Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of Zagreb Zagreb, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Raguž
authors.affiliation: Division of Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland.
authors.forename: Elda
authors.initials: E
authors.lastname: Fischi-Gómez
authors.affiliation: Ludmer Centre for Neuroinformatics, McGill Centre for Integrative Neuroscience, Department of Biomedical Engineering, Montreal Neurological Institute, Montreal, McGill University Montreal, QC, Canada.
authors.forename: Sherif
authors.initials: S
authors.lastname: Karama
authors.affiliation: Division of Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland.
authors.forename: Petra S
authors.initials: PS
authors.lastname: Huppi
authors.affiliation: Ludmer Centre for Neuroinformatics, McGill Centre for Integrative Neuroscience, Department of Biomedical Engineering, Montreal Neurological Institute, Montreal, McGill University Montreal, QC, Canada.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Evans
authors.affiliation: Department of Developmental Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of Zagreb Zagreb, Croatia.
authors.forename: Ivica
authors.initials: I
authors.lastname: Kostovic
keywords: cerebral cortex; cortical plate; human fetal brain; subplate