Harmonized Protocol for Subfield Segmentation in the Hippocampal Body on High-Resolution in vivo MRI from the Hippocampal Subfields Group (HSG)

Daugherty, A. M.; Carr, V.; Canada, K.; Radman, G.; Brown, T.; Augustinack, J.; Amunts, K.; Bakker, A.; Berron, D.; Burggren, A.; Chetelat, G.; de Flores, R.; Ding, S.-L.; Huang, Y.; Insausti, R.; Johnson, E.; Kanel, P.; Keresztes, A.; Kedo, O.; Kennedy, K. M.; Lee, J.; Malykhin, N.; Martinez, A.; Mueller, S.; Mulligan, E.; Ofen, N.; Palombo, D.; Pasquini, L.; Pluta, J.; Raz, N.; Riggins, T.; Rodrigue, K. M.; Saifullah, S.; Schlichting, M. L.; Stark, C.; Wang, L.; Yushkevich, P.; La Joie, R.; Wisse, L.; Olsen, R.; the Alzheimers Disease Neuroimaging Initiative,; the Hippocampal Subfields Gro

doi:10.1101/2025.04.29.651039

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bioRxiv · 10.1101/2025.04.29.651039

Harmonized Protocol for Subfield Segmentation in the Hippocampal Body on High-Resolution in vivo MRI from the Hippocampal Subfields Group (HSG)

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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 tesla 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 data set labeled by multiple expert neuroanatomists. With broad participation of the research community, we voted on the segmentation protocol via 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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Daugherty, A. M., Carr, V., Canada, K., Radman, G., Brown, T., Augustinack, J., Amunts, K., Bakker, A., Berron, D., Burggren, A., Chetelat, G., de Flores, R., Ding, S.-L., Huang, Y., Insausti, R., Johnson, E., Kanel, P., Keresztes, A., Kedo, O., Kennedy, K. M., Lee, J., Malykhin, N., Martinez, A., Mueller, S., Mulligan, E., Ofen, N., Palombo, D., Pasquini, L., Pluta, J., Raz, N., Riggins, T., Rodrigue, K. M., Saifullah, S., Schlichting, M. L., Stark, C., Wang, L., Yushkevich, P., La Joie, R., Wisse, L., Olsen, R., the Alzheimers Disease Neuroimaging Initiative,, the Hippocampal Subfields Gro. 2025-05-04. Harmonized Protocol for Subfield Segmentation in the Hippocampal Body on High-Resolution in vivo MRI from the Hippocampal Subfields Group (HSG). https://doi.org/10.1101/2025.04.29.651039

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