Relationship between hippocampal atrophy and neuropathology markers: A 7T MRI validation study of the EADC‐ADNI Harmonized Hippocampal Segmentation Protocol

Abstract

Objective The pathologic validation of European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Center Harmonized Hippocampal Segmentation Protocol (HarP). Methods Temporal lobes of nine Alzheimer's disease (AD) and seven cognitively normal subjects were scanned post-mortem at 7 Tesla. Hippocampal volumes were obtained with HarP. Six-micrometer-thick hippocampal slices were stained for amyloid beta (Aβ), tau, and cresyl violet. Hippocampal subfields were manually traced. Neuronal counts, Aβ, and tau burden for each hippocampal subfield were obtained. Results We found significant correlations between hippocampal volume and Braak and Braak staging (ρ = −0.75, P = .001), tau (ρ = −0.53, P = .034), Aβ burden (ρ = −0.61, P = .012), and neuronal count (ρ = 0.77, P < .001). Exploratory subfield-wise significant associations were found for Aβ in CA1 (ρ = −0.58, P = .019) and subiculum (ρ = −0.75, P = .001), tau in CA2 (ρ = −0.59, P = .016), and CA3 (ρ = −0.5, P = .047), and neuronal count in CA1 (ρ = 0.55, P = .028), CA3 (ρ = 0.65, P = .006), and CA4 (ρ = 0.76, P = .001). Conclusions The observed associations provide the pathological confirmation of hippocampal morphometry as a valid biomarker for AD and the pathologic validation of HarP.

Detection of volume alterations in hippocampal subfields of rats under chronic unpredictable mild stress using 7T MRI: A follow‐up study

“…Traditionally, hippocampal volumetry considers the hippocampus as a single anatomical entity and, thus, only provides a global volumetric measure. However, the hippocampal formation is an anatomically complex structure that is composed of multiple subfields . This multilateral structure is classically composed of the hippocampal CA1, CA2, and CA3 subfields, the dentate gyrus (DG), and the subiculum .…”

“…However, the hippocampal formation is an anatomically complex structure that is composed of multiple subfields. 11 This multilateral structure is classically composed of the hippocampal CA1, CA2, and CA3 subfields, the dentate gyrus (DG), and the subiculum. 12 As different cellular and molecular characteristics in hippocampal subfields, 13 these subfields are regarded as differentially vulnerable to processes associated with stress and conditions like depression.…”

Tractostorm: The what, why, and how of tractography dissection reproducibility

“…The field of manual tractography segmentation is decades behind fields such as gray nuclei or hippocampi manual segmentation on this matter. The latter has been refining segmentation protocols for the past decade and has already reached the state harmonized segmentation protocol and was evaluated with reproducibility in various settings (Apostolova et al, ; Boccardi et al, , ; Frisoni et al, ; Wisse et al, ).…”

Longitudinal trajectory of Amyloid‐related hippocampal subfield atrophy in nondemented elderly

“…Furthermore, given the association between tau deposition and atrophy in the whole hippocampus or hippocampal subfields (Apostolova et al, ), hippocampal subfield atrophy might be contributed by hippocampal tau deposition, which coincides with neocortex Aβ accumulation in early stage (Braak, Alafuzoff, Arzberger, Kretzschmar, & Del Tredici, ). Supporting preliminary evidence from ADNI MCI group suggested that Aβ‐associated progressive hippocampal subfield atrophy was more pronounced in MCI with p‐tau positivity, but not in MCI with p‐tau negativity (Table Se‐14).…”

“…However, similar results were observed between datasets. Secondly, other variables may also contribute to hippocampal subfield atrophy and disease progression (e.g., tau pathology and cerebrovascular factors) in addition to Aβ (Apostolova et al, ; den Heijer et al, ). Future studies need to take into consideration the spatial quantification of Aβ instead of an average Aβ burden, and determine the contributing variables and the temporal relationships underlying disease progression.…”