# A harmonized medial temporal lobe subregion segmentation protocol: an essential element for dementia research

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $677,689

## Abstract

The hippocampus and the parahippocampal region of the medial temporal lobe (MTL) consist of
anatomically and functionally distinct subregions that are selectively targeted by different pathological
processes in neurodegenerative disorders, such as Alzheimer’s disease (AD) and semantic variant Primary
Progressive Aphasia (svPPA). In AD, in vivo MRI studies investigating MTL subregions have often shown
mixed findings that are inconsistent with post-mortem pathology studies. These inconsistencies likely result
from the lack of validity and standardization in MTL segmentation approaches. In svPPA, MTL subregions are
severely affected, and automated tools fail to segment the subregions accurately. Sufficient spatial resolution
of imaging voxels is required to visualize the internal MTL structures and landmarks that are critical for valid
segmentation of the subregions. While more than 15,000 high-resolution scans have been collected worldwide,
the lack of standardization among MTL subregional segmentation protocols is still a significant barrier.
Variability in the definition of the MTL subregional boundaries among existing segmentation protocols have
contributed to the conflicting findings in the field. This proposal seeks to accelerate progress made by our
group, the Hippocampal Subfields Group, and complete our standardized, valid, and reliable harmonized
protocol for the segmentation of MTL subregions in high-resolution MRI scans. We will leverage our ongoing,
successful efforts, and evaluate the proposed harmonized protocol in scans from multicentric datasets. In Aim
1, we will finalize our harmonized segmentation protocol that is a) based on a large histology dataset and
developed in collaboration with neuroanatomists, b) assessed by the larger community to reach consensus, c)
tested for reliability, and d) implemented in an existing automated software program. In Aim 2, we will validate
the harmonized protocol in early-stage AD through associations with markers of specific pathologies: a) test for
anatomical specificity of the associations between atrophy rates across MTL subregions to PET measures of
MTL tau-pathology and markers of cardiovascular risk in patients with Mild Cognitive Impairment and cerebral
β-amyloid. In Aim 3, we will further evaluate the validity and utility of the harmonized protocol in svPPA by
performing manual segmentation of the MTL subregions using the HSG protocol and testing for anatomical
specificity of volume atrophy. In Aim 4, we will facilitate wide adoption of our protocol by providing training and
education materials, in-person workshops for manual and automated segmentation, and making outcome
measures publicly available. Our valid, reliable, and reproducible protocol for MTL subregions segmentation
will benefit groups worldwide that have and continue to collect thousands of high-resolution data to study a
variety of neurological and psychiatric conditions. It also lays the foundation for future research on ho...

## Key facts

- **NIH application ID:** 10799688
- **Project number:** 5R01AG070592-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Rosanna Kathleen Olsen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $677,689
- **Award type:** 5
- **Project period:** 2022-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799688

## Citation

> US National Institutes of Health, RePORTER application 10799688, A harmonized medial temporal lobe subregion segmentation protocol: an essential element for dementia research (5R01AG070592-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10799688. Licensed CC0.

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