Fetal Hippocampal Development: Analysis by Magnetic Resonance Imaging Volumetry

Abstract

The hippocampal formation plays an important role in learning and memory, however data on its development in utero in humans is limited. This study was performed to evaluate hippocampal development in healthy fetuses using 3D reconstructed magnetic resonance imaging (MRI). A cohort of 20 healthy pregnant women underwent prenatal MRI at a median gestational age of 24.9 weeks (range 21.3-31.9 weeks); 6 of the women also had a second fetal MRI performed at a 6 week interval. Routine 2D ultrafast T2-weighted images were used to reconstruct a 3D volume image, which was then used to manually segment the right and left hippocampi. Total hippocampal volume was calculated for each subject and compared against gestational age. There was a linear increase in total hippocampal volume with increasing gestational age (P<0.001). For subjects scanned twice, there was an increase in hippocampal size on the second fetal MRI (P=0.0004). This represents the first volumetric study of fetal hippocampal development in vivo. This normative volumetric data will be helpful for future comparison studies of suspected developmental abnormalities of hippocampal structure and function.

Development of the human fetal hippocampal formation during early second trimester

“…Others also defined the HF as comprised of a variety of cytoarchitectonic fields including the dentate gyrus, the hippocampus (Cornu Ammonis), the subiculum, presubiculum, and parasubiculum and the entorhinal cortex (Amaral, 1999; Insausti et al, 2010). In consideration of the fetal MR imaging and prior studies (Amaral and Insausti, 1990; Naidich et al, 1987a, 1987b; Adamsbaum, 2001; Jacob et al, 2011; Müller and O'Rahilly, 1994), as well as the study ‘Hippocampal and Limbic Terminology’ (Bronen, 1992), the term‘Hippocampal formation’ was defined to include the dentate gyrus, the Cornu Ammonis, the subiculum, the fimbria and the alveus in this study. We also use the term ‘Cornu Ammonis’ to replace the above ‘Hippocampus’ to avoid confusion in nomenclature.…”

“…The left HF was always segmented before the right. The anatomical borders used for segmentation of the HF were based on prior studies (Kier et al, 1997; Amaral, 1999; Naidich et al, 1987a, 1987b; Malykhin et al, 2007; Watson et al, 1992; Jacob et al, 2011) and the ‘Atlas of Human Central Nervous System Development’ (Bayer and Altman, 2004, 2005) and were traced from the anterior head to the posterior tail using both axial and sagittal planes. Note that although the HF in this paper was comprised of the dentate gyrus (DG), Cornu Ammonis (CA), fimbria, alveus, and subiculum, these structures were indistinguishable (or partly distinguishable) by fetal MR imaging and thus were roughly sampled as a whole complex.…”

“…Development of the human fetal HF is a subject of increasing interest as hippocampal injury or deviation of the HF from its normal development trajectory may be a contributor to the neurodevelopmental burden of affected individuals (Sizonenko et al, 2006; Abernethy et al, 2002; Jacob et al, 2011). The human HF comprises a considerable number of complex substructures, including the dentate gyrus, the Cornu Ammonis, the subiculum, and the associated white matter tracts, such as the fimbria and the alveus (Naidich et al, 1987a; Insausti et al, 2010; Amaral, 1999; Bronen, 1992).…”

“…Volumetric studies of the HF have been performed in adult populations and progressively in neonates and fetuses (Jacob et al, 2011; Pruessner et al, 2000; Thompson et al, 2008, 2009). A linear trajectory of hippocampal volume increase was found in healthy fetuses (Jacob et al, 2011) and preterm and full-term infants were found to have larger right hippocampi (Thompson et al, 2009). Shape analysis, on the other hand, has the potential of identifying local surface changes or developmental states of brain (sub) regions, such as hippocampi (Thompson et al, 2004; Tae et al, 2011).…”

Multi-atlas multi-shape segmentation of fetal brain MRI for volumetric and morphometric analysis of ventriculomegaly

“…Three-dimensional volumetric reconstruction has significantly improved the capacity of fetal MRI in the analysis of fetal brain development in-utero , for example in accurate brain volumetry (Gholipour et al, 2011), as well as in-vivo analysis of hippocampal development (Jacob et al, 2011) and cortical maturation (Clouchoux et al, 2011). Significant clinical applications such as quantitative analysis of the early brain development and the diagnosis and prognosis of brain anomalies are expected to be dramatically facilitated by using this technology.…”