Brain Topography

, Volume 31, Issue 6, pp 949–962 | Cite as

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

  • Mark A. FraserEmail author
  • Marnie E. Shaw
  • Kaarin J. Anstey
  • Nicolas Cherbuin
Original Paper


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.


Hippocampus Longitudinal FreeSurfer Manual tracing Normal ageing Magnetic resonance imaging 



The authors are grateful to Chantal Réglade-Meslin, Jerome Maller, Peter Butterworth, Simon Easteal, Helen Christensen, Patricia Jacomb, Karen Maxwell, and the PATH interviewers. The study was supported by an Australian Government Research Training Program (RTP) Scholarship, National Health and Medical Research Council (NHMRC) Grant Nos. 973302, 179805,350833 157125, and Australian Research Council (ARC) Grant No. 130101705. Kaarin Anstey was funded by NHMRC Fellowship No.1002560. This research was partly undertaken on the National Computational Infrastructure (NCI) facility in Canberra, Australia, which is supported by the Australian Commonwealth Government. The authors declare no competing financial interests. This research is supported by an Australian Government Research Training Program (RTP) Scholarship. This study is NOT industry sponsored.

Author Contributions

MAF contributed to the design of the study, conducted all statistical analyses, and managed all aspects of manuscript preparation and submission. MES contributed to the design of the study and the statistical analyses, provided methodological input and theoretical expertise, and contributed to writing and editing of the manuscript. KJA contributed to the design of the study, provided methodological input and theoretical expertise, and contributed to writing and editing of the manuscript. NC contributed to the design of the study and the statistical analyses, provided methodological input and theoretical expertise, and contributed to writing and editing of the manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors have reported no conflicts of interest.

Supplementary material

10548_2018_659_MOESM1_ESM.docx (180 kb)
Supplementary material 1 (DOCX 179 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centre for Research on Ageing, Health and WellbeingAustralian National University, FloreyCanberraAustralia
  2. 2.College of Engineering & Computer ScienceAustralian National UniversityCanberraAustralia

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