Evidence map›Paper›PMID 40734544›Full record

ArticleHippocampus2025

Developing an Anatomically Valid Segmentation Protocol for Anterior Regions of the Medial Temporal Lobe for Neurodegenerative Diseases.

Niyousha Sadeghpour, Sydney A Lim, Anika Wuestefeld, Amanda E Denning, Ranjit Ittyerah, Winifred Trotman, Eunice Chung, Shokufeh Sadaghiani, Karthik Prabhakaran, Madigan L Bedard and 23 more

Abstract read
In one paragraph

Article in Hippocampus, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors.

Niyousha SadeghpourDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0001-8665-0335
Sydney A LimDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Anika WuestefeldDepartment of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Amanda E DenningDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ranjit IttyerahDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Winifred TrotmanDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Eunice ChungDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Shokufeh SadaghianiDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Karthik PrabhakaranDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Madigan L BedardDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Daniel T OhmDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Emilio Artacho-PérulaHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.ORCID 0000-0002-2201-576X
Maria Mercedes Iñiguez de Onzoño MartinHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.
Monica MuñozHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.ORCID 0000-0002-5530-2394
Francisco Javier Molina RomeroHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.
José Carlos Delgado GonzálezHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.
María Del Arroyo JiménezHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.
Maria Del Marcos RabalHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.
Ana María Insausti SerranoHealth Sciences Faculty, Public University of Navarre, Spain.ORCID 0000-0002-4707-8046
Noemí Vilaseca GonzálezHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.
Sandra Cebada SánchezHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.
Carlos de la Rosa PrietoHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.
Ricardo InsaustiHuman Neuroanatomy Laboratory, Neuromax CSIC Associated Unit, University of Castilla-La Mancha and Institute for Biomedicine, Albacete, Spain.
Corey McMillanDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-7581-6405
Edward B LeeDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-4589-1180
John A DetreDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Sandhitsu R DasDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Long XieDepartment of Digital Technology and Innovation, Siemens Healthineers, Princeton, New Jersey, USA.ORCID 0000-0002-7184-7028
M Dylan TisdallDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-0454-3112
David J IrwinDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
David A WolkDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Paul A YushkevichDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0001-8543-4016
Laura E M WisseDepartment of Clinical Sciences Lund, Lund University, Lund, Sweden.ORCID 0000-0001-7504-3943

Funding

Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8M
Understanding Environmental Contributions to Heterogeneity in bvFTD.P01AG066597 · NIA · UNIVERSITY OF PENNSYLVANIA · PI David John Irwin, Corey T McMillan · 2020 to 2026
$18.8M
Project IV "Tackling Heterogeneity of Cognitive Trajectory in LBD"U19AG062418 · NIA · UNIVERSITY OF PENNSYLVANIA · PI TROJANOWSKI, JOHN Q. · 2019 to 2023
$18.1M
Ex Vivo Imaging of the Aging Brain to Discover Morphology/Pathology AssociationsR01AG056014 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Paul A. Yushkevich · 2017 to 2026
$4.5M
Biological Aging Contributions to Molecular Pathology and NeurodegenerationR01AG066152 · NIA · UNIVERSITY OF PENNSYLVANIA · PI MCMILLAN, COREY T · 2019 to 2023
$3.8M
Microscopic and Large-Scale Networks of Molecular Pathology in Frontotemporal Lobar DegenerationR01NS109260 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI IRWIN, DAVID JOHN · 2019 to 2023
$3.8M
A harmonized medial temporal lobe subregion segmentation protocol: an essential element for dementia researchR01AG070592 · NIA · WAYNE STATE UNIVERSITY · PI Ana Marie Daugherty, Rosanna Kathleen Olsen · 2022 to 2026
$3.5M
Ex Vivo Imaging of the Aging Brain to Discover Morphology/Pathology AssociationsRF1AG056014 · NIA · UNIVERSITY OF PENNSYLVANIA · PI YUSHKEVICH, PAUL A. · 2023 to 2023
$2.1M
Imaging Iron-Rich Pathology to Monitor and Diagnose FLTD SubtypesR01AG080734 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Matthew Dylan Tisdall · 2023 to 2026
$1.5M
Improving the sensitivity and specificity of MRI-based biomarkers in Alzheimer's diseaseR01AG069474 · NIA · UNIVERSITY OF PENNSYLVANIA · PI WOLK, DAVID A, YUSHKEVICH, PAUL A. · 2024 to 2025
$1.4M
Crafoordska Stiftelsen 20230790MultiParkNIA NIH HHS P01 AG066597NIA NIH HHS P30 AG072979NIA NIH HHS R01 AG056014NIA NIH HHS R01 AG066152NIA NIH HHS R01 AG069474NIA NIH HHS R01 AG070592NIA NIH HHS R01 AG080734NIA NIH HHS RF1 AG056014NIA NIH HHS U19 AG062418NIH HHS P01-AG066597NIH HHS P30-AG072979NIH HHS R01-AG066152NIH HHS R01 AG069474NIH HHS R01-AG070592NIH HHS R01-AG080734NIH HHS R01-NS109260NIH HHS RF1-AG056014NIH HHS U19-AG062418NINDS NIH HHS R01 NS109260Swedish Alzheimer Foundation AF-980872UCLM Intramural Grant 2022-GRIN-34392
6 · The paper itself

Abstract

The anterior portion of the medial temporal lobe (MTL) is one of the first regions targeted by pathology in sporadic Alzheimer's disease (AD) and limbic-predominant age-related TDP-43 encephalopathy (LATE) indicating a potential for metrics from this region to serve as imaging biomarkers. Leveraging a unique post-mortem dataset of histology and magnetic resonance imaging (MRI) scans, we aimed to (1) develop an anatomically valid segmentation protocol for anterior entorhinal cortex (ERC), Brodmann area (BA) 35, and BA36 for in vivo 3 T MRI and (2) incorporate this protocol in an automated approach. We included 20 cases (61-97 years old, 50% females) with and without neurodegenerative diseases (11 vs. 9 cases) to ensure generalizability of the developed protocol. Digitized MTL Nissl-stained coronal histology sections from these cases were annotated and registered to same-subject post-mortem MRI. The protocol was developed by determining the location of histological borders of the MTL cortices in relation to anatomical landmarks. Subsequently, the protocol was applied to 15 cases twice, with a 2-week interval, to assess intra-rater reliability with the Dice Similarity Index (DSI). Thereafter, it was implemented in our in-house Automatic Segmentation of Hippocampal Subfields (ASHS)-T1 approach and evaluated with DSIs. The anterior histological border distances of ERC, BA35 and BA36 were evaluated with respect to various anatomical landmarks, and the distance relative to the beginning of the hippocampus was chosen. To formulate segmentation rules, we examined the histological sections for the location of borders in relationship to anatomical landmarks in the coronal sections. The DSI for the anterior MTL cortices for the intra-rater reliability was 0.85-0.88, and for the ASHS-T1 against the manual segmentation, it was 0.62-0.65. We developed a reliable segmentation protocol and incorporated it in an automated approach. Given the vulnerability of the anterior MTL cortices to tau deposition in AD and LATE, the updated approach is expected to improve imaging biomarkers for these diseases.

Indexed as

Neurodegenerative DiseasesTemporal LobeAgedAged, 80 and overAlzheimer DiseaseFemaleHumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMiddle AgedAlzheimer's diseaseimaging biomarkersmedial temporal lobe

Identifiers

PMID40734544
PMCPMC12361719

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.