Amygdalar nuclei and hippocampal subfields on MRI: Test-retest reliability of automated volumetry across different MRI sites and vendors

G. Quattrini, M. Pievani, J. Jovicich, M. Aiello, N. Bargalló, F. Barkhof, D. Bartres-Faz, A. Beltramello, F.B. Pizzini, O. Blin, R. Bordet, M. Caulo, M. Constantinides, M. Didic, A. Drevelegas, A. Ferretti, U. Fiedler, P. Floridi, H. Gros-Dagnac, T. HenschK.-T. Hoffmann, J.P. Kuijer, R. Lopes, C. Marra, B.W. Müller, F. Nobili, L. Parnetti, P. Payoux, A. Picco, J.-P. Ranjeva, L. Roccatagliata, P.M. Rossini, M. Salvatore, P. Schonknecht, B.H. Schott, J. Sein, A. Soricelli, R. Tarducci, M. Tsolaki, P.J. Visser, J. Wiltfang, J.C. Richardson, G.B. Frisoni, M. Marizzoni, PharmaCog Consortium

Research output: Contribution to journalArticlepeer-review


Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1–90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. Results: Significant MRI site and vendor effects (p ​< ​.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman's r correlations >0.43, p ​< ​1.39E-36). In particular, volumes larger than 200 ​mm3 (for amygdalar nuclei) and 300 ​mm3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε ​< ​5% and DICE ​> ​0.80). Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials. © 2020 The Authors
Original languageEnglish
Article number116932
Number of pages14
Publication statusPublished - 2020


  • Amygdalar nuclei
  • FreeSurfer
  • Hippocampal subfields
  • Multicenter MRI study
  • Reliability analysis
  • accessory basal nucleus
  • adult
  • aged
  • amygdala
  • Article
  • automation
  • basal amygdala
  • brain size
  • central nucleus (amygdala)
  • cohort analysis
  • controlled study
  • cortical amygdala
  • dentate hilus
  • hippocampal CA1 region
  • hippocampal CA3 region
  • hippocampal fimbria
  • hippocampal tail
  • hippocampus
  • hippocampus molecular layer
  • human
  • human experiment
  • image processing
  • image segmentation
  • lateral amygdala
  • medial amygdala
  • normal human
  • nuclear magnetic resonance imaging
  • paralaminar nucleus
  • parasubiculum
  • presubiculum
  • priority journal
  • reproducibility
  • subiculum
  • test retest reliability
  • volumetry


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