Harmonized Protocol for Subfield Segmentation in the Hippocampal Body on High‐Resolution In Vivo <scp>MRI</scp> From the Hippocampal Subfields Group ( <scp>HSG</scp> )

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 T<sub>2</sub>-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.

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Journal
Hippocampus
Published
2026-02-03
DOI
https://doi.org/10.1002/hipo.70073
Primary Topic
Memory and Neural Mechanisms
Type
article
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article

Harmonized Protocol for Subfield Segmentation in the Hippocampal Body on High‐Resolution In Vivo MRI From the Hippocampal Subfields Group ( HSG )

Nikolai Malykhin, Ana M. Daugherty, Gustaf Rådman, Lorenzo Pasquini et al.
Hippocampus
Memory and Neural Mechanisms
article

Harmonized Protocol for Subfield Segmentation in the Hippocampal Body on High‐Resolution In Vivo MRI From the Hippocampal Subfields Group ( HSG )

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

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 T<sub>2</sub>-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.

HippocampusVol. 36(2)
Eötvös Loránd University (HU), Georgia Institute of Technology (US), University of British Columbia (CA), Johns Hopkins University (US), University of Alberta (CA), Inserm (FR), The University of Texas at Dallas (US), Forschungszentrum Jülich (DE), University of California, San Francisco (US), University of Oregon (US), University of Toronto (CA), Wayne State University (US), Lund University (SE), University of California, Irvine (US), University of Massachusetts Amherst (US), University of Michigan (US), German Center for Neurodegenerative Diseases (DE), Baycrest Hospital (CA), University of Illinois Chicago (US), Massachusetts General Hospital (US), Düsseldorf University Hospital (DE), University Memory and Aging Center (US), Normandie Université (FR), Michigan United (US), Max Planck Institute for Human Development (DE), Jülich Aachen Research Alliance (DE), Allen Institute (US), Heinrich Heine University Düsseldorf (DE), San Jose State University (US), Stony Brook University (US), University of Maryland, College Park (US), University of Pennsylvania (US), University of California, Davis (US), Université de Caen Normandie (FR)
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