Postmortem MRI signature of Hippocampal Sclerosis of Aging
Bibliographic record
Abstract
Abstract Background Hippocampal Sclerosis of aging (HS) refers to age‐related selective neuronal loss and gliosis in hippocampal cornu ammonis 1 (CA1) and subiculum that is out of proportion to tau pathology in Alzheimer’s Disease (AD). HS is related to cognitive decline and memory impairments separately from other neurodegenerative pathologies. To date, in vivo imaging biomarkers of HS of aging are non‐existent, and their development would greatly improve diagnosis and prognosis in memory clinics. We therefore aimed to characterize the magnetic resonance imaging (MRI) signature of HS among autopsy confirmed cases of HS. Method Data consisted of same‐subject histological Nissl‐stained slices and postmortem MRI (0.2mm isotropic) acquired from 27 subjects at the University of Pennsylvania and University Castilla‐La Mancha. Based on neuropathological assessment, cases were grouped into HS (N = 5), intermediate to high AD neuropathologic change without HS (N = 10) and limited or no neuropathological burden (N = 12). We manually measured grey matter thickness and GM/WM intensity ratio in select locations across the hippocampal head, body, and tail. We also obtained more global structural measures from hippocampal subfields using an automated postmortem atlas‐based segmentation algorithm. Result Qualitatively, HS is clearly noticeable as cortical thinning and hypointense signal (approximating white matter) on postmortem MRI across the CA1 and subiculum, particularly anteriorly closer to the border between CA1/subiculum (Figure 1). Manual thickness measures showed complete separation between the HS group and the two reference groups across both the hippocampal head and body, and a less pronounced difference in the tail. Global structural measures from automated segmentations corroborated these group differences showing complete separation in CA1 thickness and significant differences in subiculum and the white matter layer of CA1 (Stratum Radiatum Lacunosum Moleculare, SRLM). Conclusion In MRI, HS is marked by hypointense voxels and cortical thinning across CA1 and subiculum. Both local manual thickness measurements and thickness measures of whole subfields derived from automatic segmentations provided promising results. As a next step, we plan to perform similar measurements on antemortem MRI of the same subjects, with the hopes of making progress toward an in vivo MRI biomarker of HS.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".