MRI Volumetric Analysis of the Hypothalamus and Limbic System across the Pediatric Age Span

Literature is scarce regarding volumetric measures of limbic system components across the pediatric age range. The purpose of this study is to remedy this scarcity by reporting continuous volumetric measurements of limbic system components, and to provide consistent stratification data including age-related trajectories and sex-related differences in the pediatric age range in order to improve the recognition of structural variations that might reflect pathology.

In this retrospective study, MRI sequences of children with normal clinical MRI examinations of the brain acquired between January 2010 and December 2019 were included. Isotropic 3D T1-weighted were processed using FreeSurfer version 7.3. Total brain volume and volumes of the limbic system including the hippocampus, parahippocampal gyrus, amygdala, hypothalamus, cingulate gyrus, entorhinal cortex, anteroventral thalamic nucleus, and whole thalamus were assessed. Parcellated output was displayed with the respective label map overlay and images were visually inspected for accuracy of regional segmentation results. Continuous data are provided as mean and standard deviation with quadratic trendlines and as mean and 95% confidence intervals. Categorical data are presented as integers and percentages (%).

A total of 724 children (401 female, 55.4%), with a mean age at time of MRI of 10.9 ± 4.2 years (range: 1.9-18.2 years), were included in the study. For females, the total brain volume increased from 955 ± 70 mL at the age of 2-3 years to 1140 ± 110 mL at the age of 17-18 years. Similarly, the total brain volume increased for males from 1004 ± 83 mL to 1263 ± 96 mL. The maximum volume was noted at 11-12 years for females (1188 ± 90 mL) and at 14-15 years for males (1310 ± 159 mL). Limbic system structures reached their peak volume more commonly between the 13-14 years to 17-18 years age groups. The male cingulate gyrus, entorhinal cortex, and anteroventral thalamic nucleus reached peak volume before or at 9-10 years.

This study provides unique age- and sex-specific volumes of the components of the limbic system throughout the pediatric age range to serve as normal values in comparative studies. Quantification of volumetric abnormalities of the limbic system on brain MRI may offer insights into phenotypical variations of diseases and may help elucidate new pathological phenotypes.