Longitudinal Assessment of Hippocampal Atrophy in Midlife and Early Old Age: Contrasting Manual Tracing and Semi-automated Segmentation (FreeSurfer).

It is important to have accurate estimates of normal age-related brain structure changes and to understand how the choice of measurement technique may bias those estimates. We compared longitudinal change in hippocampal volume, laterality and atrophy measured by manual tracing and FreeSurfer (version 5.3) in middle age (n = 244, 47.2[1.4] years) and older age (n = 199, 67.0[1.4] years) individuals over 8 years. The proportion of overlap (Dice coefficient) between the segmented hippocampi was calculated and we hypothesised that the proportion of overlap would be higher for older individuals as a consequence of higher atrophy. Hippocampal volumes produced by FreeSurfer were larger than manually traced volumes. Both methods produced a left less than right volume laterality difference. Over time this laterality difference increased for manual tracing and decreased for FreeSurfer leading to laterality differences in left and right estimated atrophy rates. The overlap proportion between methods was not significantly different for older individuals, but was greater for the right hippocampus. Estimated middle age annualised atrophy rates were - 0.39(1.0) left, 0.07(1.01) right, - 0.17(0.88) total for manual tracing and - 0.15(0.69) left, - 0.20(0.63) right, - 0.18(0.57) total for FreeSurfer. Older age atrophy rates were - 0.43(1.32) left, - 0.15(1.41) right, - 0.30 (1.23) total for manual tracing and - 0.34(0.79) left, - 0.68(0.78) right, - 0.51(0.65) total for FreeSurfer. FreeSurfer reliably segments the hippocampus producing atrophy rates that are comparable to manual tracing with some biases that need to be considered in study design. FreeSurfer is suited for use in large longitudinal studies where it is not cost effective to use manual tracing.