Underdevelopment of the Human Hippocampus in Callosal Agenesis: An In Vivo Fetal MRI Study

Abstract

Background and purpose: In subjects with agenesis of the corpus callosum, a variety of structural brain alterations is already present during prenatal life. Quantification of these alterations in fetuses with associated brain or body malformations (corpus callosum agenesis and other related anomalies) and so-called isolated cases may help to optimize the challenging prognostic prenatal assessment of fetuses with corpus callosum agenesis. This fetal MR imaging study aimed to identify differences in the size of the prenatal hippocampus between subjects with isolated corpus callosum agenesis, corpus callosum agenesis and other related anomalies, and healthy controls.

Materials and methods: Eighty-five in utero fetal brain MR imaging scans, (20-35 gestational weeks) were postprocessed using a high-resolution algorithm. On the basis of multiplanar T2-TSE sequences, 3D isovoxel datasets were generated, and both hippocampi and the intracranial volume were segmented.

Results: Hippocampal volumes increased linearly with gestational weeks in all 3 groups. One-way ANOVA demonstrated differences in hippocampal volumes between control and pathologic groups (isolated corpus callosum agenesis: left, P = .02; right, P = .04; corpus callosum agenesis and other related anomalies: P < .001). Differences among the pathologic groups were also present for both sides. Intracranial volume and right and left hippocampal volume ratios were different between corpus callosum agenesis cases and controls (P < .001). When we corrected for intracranial volume, no differences were found between corpus callosum agenesis and other associated anomalies and isolated corpus callosum agenesis (left, P = .77; right, P = .84). Hippocampal size differences were more pronounced at a later gestational age.

Conclusions: Callosal agenesis apparently interferes with the normal process of hippocampal formation and growth, resulting in underdevelopment, which could account for certain learning and memory deficits in individuals with agenesis of the corpus callosum in later life.

Fig 1.

In vivo T2-weighted images of a control fetal brain, at 30 GW. An example of 3D-reconstructed MR imaging and segmentation borders for the left (red) and right (green) hippocampus in sagittal (A), axial (B), and coronal (C) views.

Fig 2.

Axial view of a 3D surface model of the left (red) and right (green) hippocampus at 23 GW (A) and 30 GW (B).

Fig 3.

Scatterplots present absolute hippocampal volumes of controls, iACC, and aACC for the left (A) and right (B) hippocampus.

Fig 4.

Moderation effects of age groups on volume group differences were found for the left (A) and right (B) hippocampal volumes but not for the ratios of absolute hippocampal volume and ICV (C and D).