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

Abstract

Although the hippocampus is one of the most studied structures in the human brain, limited quantitative data exist on its 3D organization, anatomical variability, and effects of disease on its subregions. Histological studies provide restricted reference information due to their 2D nature. In this paper, high-resolution (∼200 × 200 × 200 μm) 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.

The Role of MRI Biomarkers and Their Interactions with Cognitive Status and APOE ε4 in Nondemented Elderly Subjects

“…Apostolova et al [12, 13] reported that AD patients had CA1-3 region atrophy and CA1 atrophy can predict the conversion of MCI patients to AD. These results have also been reported in several other studies [14, 15]. Besides, some other studies indicate that the subiculum and presubiculum may also play important roles.…”

Coordination of human hippocampal sharpwave-ripples during NREM sleep with cortical theta bursts, spindles, downstates and upstates

“…After implantation, electrodes were located by aligning post-implant CT to preoperative 3D T1weighted structural MRI with ~1mm 3 voxel size (Dykstra et al, 2012), using 3D Slicer (RRID:SCR_005619). This allows visualization of individual contacts with respect to HC crosssectional anatomy, which was interpreted in reference to published atlases (Duvernoy, 1988;Ding and Van Hoesen, 2015;Adler et al, 2018). While the spatial resolution of T1 MRI is limited, the body of HC has a highly regular anatomical orientation with respect to the temporal horn of the lateral ventricle.…”

Hippocampal subfields revealed through unfolding and unsupervised clustering of laminar and morphological features in 3D BigBrain

“…Each of these features has been described in histology (Ding & Van Hoesen, 2015;Duvernoy et al, 2013), but has not been reconstructed in a 3D model at this level of detail. For example, (Adler et al, 2018) and (Iglesias et al, 2015) both performed detailed and fully 3D segmentation of the hippocampus and its subfields using ex-vivo MRI data, with additional histological data in the same participants provided by Adler et al, Our approach extends beyond these studies by utilizing higher-resolution tracing and by using histological cues inherent in the same images. Furthermore, our manual traces and quantitative analyses fully respect the topology of the hippocampus and, in turn, the continuity of each subfield throughout the entire length of the hippocampus.…”