Publication Date

2-3-2026

Document Type

Article

Publication Title

Hippocampus

Volume

36

Issue

2

DOI

10.1002/hipo.70073

Abstract

Hippocampal subfields differentially develop and age, and they vary in vulnerability to neurodegenerative diseases. Innovation in high-resolution imaging has accelerated clinical research on human hippocampal subfields, but substantial differences in segmentation protocols impede comparisons of results across laboratories. The Hippocampal Subfields Group (HSG) is an international organization seeking to address this issue by developing a histologically valid, reliable, and freely available segmentation protocol for high-resolution T2-weighted 3 T MRI (http://www.hippocampalsubfields.com). Here, we report the first portion of the protocol focused on subfields in the hippocampal body; protocols for the head and tail are in development. The body protocol includes definitions of the internal boundaries between subiculum, Cornu Ammonis (CA) 1–3 subfields, and dentate gyrus, in addition to the external boundaries of the hippocampus apart from surrounding white matter and cerebrospinal fluid. The segmentation protocol is based on a novel histological reference dataset labeled by multiple expert neuroanatomists. With broad participation of the research community, we voted on the segmentation protocol via an online survey, which included detailed protocol information, feasibility testing, demonstration videos, example segmentations, and labeled histology. All boundary definitions were rated as having high clarity and reached consensus agreement by Delphi procedure. The harmonized body protocol yielded high inter- and intra-rater reliability. In the present paper we report the procedures to develop and test the protocol, as well as the detailed procedures for manual segmentation using the harmonized protocol. The harmonized protocol will significantly facilitate cross-study comparisons and provide increased insight into the structure and function of hippocampal subfields across the lifespan and in neurodegenerative diseases.

Keywords

Cornu Ammonis, dentate gyrus, neuroimaging, subiculum

Comments

Ana M. Daugherty, Valerie Carr, Kelsey L. Canada, Gustaf Rådman, Thackery Brown, Jean Augustinack, Katrin Amunts, Arnold Bakker, David Berron, Alison Burggren, Gael Chetelat, Robin de Flores, Song-Lin Ding, Yushan Huang, Elliott Johnson, Prabesh Kanel, Attila Keresztes, Olga Kedo, Kristen M. Kennedy, Joshua Lee, Nikolai Malykhin, Anjelica Martinez, Susanne Mueller, Elizabeth Mulligan, Noa Ofen, Daniela Palombo, Lorenzo Pasquini, John Pluta, Naftali Raz, Tracy Riggins, Karen M. Rodrigue, Samaah Saifullah, Margaret L. Schlichting, Craig Stark, Lei Wang, Paul Yushkevich, Renaud La Joie, Laura Wisse, Rosanna Olsen, Alzheimer’s Disease Neuroimaging Initiative , Hippocampal Subfields Group

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Department

Psychology

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