Assessment of human hippocampal developmental neuroanatomy by means of ex-vivo 7 T magnetic resonance imaging

• 7 T MRI provides good anatomic definition of the healthy developing hippocampus.
• Cell density and myelin content variations play a major role in generating MRI signal.
• 7 T MR data might be used as reference in the perspective of future clinical practise.

During development, the hippocampus undergoes numerous changes in its cell morphology and cyto- and myelo-architecture that begin during the fetal period and continue after birth. We investigated the developmental changes occurring in healthy fetal (20–32 gestational weeks) and post-natal human hippocampi (from 1 day to adulthood) by combining high-resolution 7 T magnetic resonance imaging (MRI) and histological and immunohistochemical analyses in order to compare variations in signal intensity with cyto- and myeloarchitectural organization. During fetal period the intensity of the T2-weighted images was related to the cell density and the subregions of Ammon's horn and dentate gyrus, characterized by densely packed neurons, were recognizable as hypointense areas. The inverse correlation between MRI signal intensity and cell density was visualized by line profile results. At the age of two post-natal weeks, the low MRI signal was still related to cell density, although thin myelinated fibers were observed in hypointense regions such as the alveus and stratum lacunosum-moleculare. The myelin content subsequently increases until the complete hippocampal myeloarchitecture is reached in adulthood. Comparison of the MRI findings and corresponding histological sections indicated that the differences in the T2-weighted images between the age of seven years and adulthood reflect the increasing density of myelinated fibers.These results provide useful information concerning the interpretation of MRI signals and the developmental changes visualized by in vivo MRI at lower field strengths, and may be used as a reference for the future use of high spatial resolution MRI in clinical practice.