Characterizing the human hippocampus in aging and Alzheimer's disease using a computational atlas derived from ex vivo MRI and histology

Authors: Daniel Adler, Laura E.M. Wisse, Ranjit Ittyerah, John Pluta, Song‐Lin Ding, Long Xie, Jiancong Wang, Salmon Kadivar, John Robinson, Theresa Schuck, John Q. Trojanowski, Murray Grossman, John A. Detre, Mark A. Elliott, Jon B. Toledo, Weixia Liu, Stephen Pickup, Michael I. Miller, Sandhitsu R. Das, David A. Wolk, Paul A. Yushkevich - Proceedings of the National Academy of Sciences, PNAS 2018 cited by 216

) ex vivo MRI scans of 31 human hippocampal specimens are combined using a groupwise diffeomorphic registration approach into a 3D probabilistic atlas that captures average anatomy and anatomic variability of hippocampal subfields. Serial histological imaging in 9 of the 31 specimens was used to label hippocampal subfields in the atlas based on cytoarchitecture. Specimens were obtained from autopsies in patients with a clinical diagnosis of Alzheimer's disease (AD; 9 subjects, 13 hemispheres), of other dementia (nine subjects, nine hemispheres), and in subjects without dementia (seven subjects, nine hemispheres), and morphometric analysis was performed in atlas space to measure effects of age and AD on hippocampal subfields. Disproportional involvement of the cornu ammonis (CA) 1 subfield and stratum radiatum lacunosum moleculare was found in AD, with lesser involvement of the dentate gyrus and CA2/3 subfields. An association with age was found for the dentate gyrus and, to a lesser extent, for CA1. Three-dimensional patterns of variability and disease and aging effects discovered via the ex vivo hippocampus atlas provide information highly relevant to the active field of in vivo hippocampal subfield imaging.