Validity of automated FreeSurfer segmentation compared to manual tracing in detecting prenatal alcohol exposure-related subcortical and corpus callosal alterations in 9-to 11-year-old children

In recent years a number of semi-automated and automated segmentation tools and brain atlases have been developed to facilitate morphometric analyses of large MRI datasets. These tools are much faster than manual tracing and demonstrate excellent test retest reliabilities. Reliabilities of automated segmentations relative to "gold standard" manual tracings have, however, been shown to vary by brain region and in different cohorts. It remains uncertain to what extent smaller brain volumes and potential changes in grey/white matter contrasts in paediatric brains impact on the performance of automated methods, and how pathology may influence performance. This study examined whether using data from automated FreeSurfer segmentation would alter our ability, compared to manual segmentation, to detect prenatal alcohol exposure (PAE)-related volume changes in subcortical regions and the corpus callosum (CC) in pre-adolescent children. High-resolution Tl-weighted images were acquired, using a sequence optimized for morphometric neuroanatomical analysis, on a Siemens 3T Allegra MRI scanner in 71 righthanded, 9- to 11-year-old children (27 fetal alcohol syndrome (FAS) and partial FAS (PFAS), 25 non-syndromal heavily exposed (HE) and 19 non-exposed controls) from a high-risk community in Cape Town, South Africa. Data from timeline follow-back interviews administered to the mothers prospectively during pregnancy were used to quantify the amount of alcohol (in ounces absolute alcohol per day, AA/day) that the children had been exposed to prenatally. Volumes of corpus callosum (CC) and bilateral caudate nuclei, hippocampi and nucleus accumbens (NA) were obtained by manual tracing and automated segmentation using both FreeSurfer versions 5.1 and 6.0. Reliability across methods was assessed using intraclass correlation (ICC) estimates for consistency and absolute agreement, and Cronbach's a. Ability to detect regions showing PAE effects was assessed separately for each segmentation method using ANOVA and linear regression of regional volumes with AA/day. Our results support findings from other studies showing excellent reliability across methods for easy-to-segment structures, such as the CC and caudate nucleus. Volumes from FreeSurfer 6.0 were smaller than those from version 5.1 in all regions except the right caudate, for which they were similar, and right hippocampus and CC, for which they were larger. Despite poor absolute agreement between methods in the NA and hippocampus, all three segmentation methods detected dose-dependent volume reductions in regions for which reliabilities on ICC consistency across methods reached at least 0.70, namely the CC, and bilateral caudate nuclei and hippocampi. PAE-related changes in the NA for which ICC consistency did not reach this minimum were inconsistent across methods and should be interpreted with caution. This is the first study to demonstrate in a pre-adolescent cohort the ability of automated segmentation with FreeSurfer to detect regional volume changes associated with pathology similar to those found using manual tracing.