The early alteration of brainstem and cerebellum, and their relationship with cerebral cortex: an in vivo fetal magnetic resonance imaging assessment.

BACKGROUND

The cerebral cortex, brainstem, and cerebellum are the primary components of the development of the nervous system. There is an interrelationship in their developmental processes. Abnormal development of the brainstem and cerebellum can cause various malformations, as well as abnormalities in cortical functional development, leading to functional disorders. Exploring the developmental patterns of the brainstem and cerebellum, as well as their relationship with the cerebral cortex, is of great significance. Therefore, this study utilized three-dimensional (3D) magnetic resonance imaging (MRI) reconstruction to investigate the growth patterns of fetal brainstem and cerebellum volumes with gestational age (GA), and explore the developmental relationship between brainstem, cerebellum, and cerebral cortex.

METHODS

This observational cross-sectional study included 172 fetuses with normal brain MRI. 3D brain images from 47 fetuses (GA 22-36 weeks) were reconstructed. The brainstem and cerebellum were manually delineated in 3D images to calculate their volumes and construct growth trajectories. Qualitative morphological assessments of the brainstem and cerebellar vermis were performed in the mid-sagittal plane, and cerebellar hemispheres were evaluated in the axial plane, to characterize structural changes across GA. The fetal cerebral cortex was automatically segmented to study the developmental relationships between brainstem and cortex, and cerebellum and cortex.

RESULTS

Pearson correlation analysis showed that the volume of brainstem and cerebellum were positively correlated with GA in normal fetuses (brainstem: r=0.75, P<0.0001; cerebellum: r=0.87, P<0.0001). GA 30 weeks marked a critical turning point in growth patterns. The 3D volumetric trajectories showed that the brainstem grew rapidly before GA 30 weeks and slowly after GA 30 weeks. Conversely, the cerebellum exhibited slow growth before GA 30 weeks and an accelerated growth after GA 30 weeks. The growth of the brainstem and cerebellum was closely related to the cerebral cortex, especially in the posterior frontal lobe, parietal lobe, and occipital cortex. Moreover, their relationship with the right hemisphere was more significant than that with the left hemisphere.

CONCLUSIONS

The 3D volume of fetal brainstem and cerebellum is closely related to GA. Establishing a normal fetal brainstem and cerebellar volume growth trajectory can help to identify abnormal growth, development, and malformations. The relationship between the development of the cerebral cortex, brainstem, and cerebellum warrants further investigation.