The EADC-ADNI harmonized protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

Giovanni B. Frisoni, Clifford R. Jack, Martina Bocchetta, Corinna Bauer, Kristian S. Frederiksen, Yawu Liu, Gregory Preboske, Tim Swihart, Melanie Blair, Enrica Cavedo, Michel J. Grothe, Mariangela Lanfredi, Oliver Martinez, Masami Nishikawa, Marileen Portegies, Travis Stoub, Chadwich Ward, Liana G. Apostolova, Rossana Ganzola, Dominik WolfFrederik Barkhof, George Bartzokis, Charles DeCarli, John G. Csernansky, Leyla Detoledo-Morrell, Mirjam I. Geerlings, Jeffrey Kaye, Ronald J. Killiany, Stephane Lehericy, Hiroshi Matsuda, John O'Brien, Lisa C. Silbert, Philip Scheltens, Hilkka Soininen, Stefan Teipel, Gunhild Waldemar, Andreas Fellgiebel, Josephine Barnes, Michael Firbank, Lotte Gerritsen, Wouter Henneman, Nikolai Malykhin, Jens C. Pruessner, Lei Wang, Craig Watsonl, Henrike Wolf, Mony Deleon, Johannes Pantel, Clarissa Ferrari, Paolo Bosco, Patrizio Pasqualetti, Simon Duchesne, Henri Duvernoy, Marina Boccardi, Marilyn S. Albert, David Bennet, Richard Camicioli, D. Louis Collins, Bruno Dubois, Harald Hampel, Tom Denheijer, Christofer Hock, William Jagust, Leonore Launer, Jerome J. Maller, Susan Mueller, Perminder Sachdev, Andy Simmons, Paul M. Thompson, Peter Jelle Visser, Lars Olof Wahlund, Michael W. Weiner, Bengt Winblad

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Background: An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance. Methods: Fourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T. Results: The agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P <.001), and physiological variability (49.2%, P <.001). Conclusions: The HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.

Original languageEnglish (US)
Pages (from-to)111-125
Number of pages15
JournalAlzheimer's and Dementia
Issue number2
StatePublished - 2015


  • Alzheimer's disease
  • Biomarkers
  • Clinical trials
  • Diagnostic criteria
  • Enrichment
  • Harmonized protocol
  • Hippocampal volumetry
  • Magnetic resonance
  • Manual segmentation
  • Standard operating procedures
  • Validation

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Health Policy
  • Developmental Neuroscience
  • Epidemiology


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