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

Sadeghpour, Niyousha ; Lim, Sydney A ; Wuestefeld, Anika LU orcid ; Denning, Amanda E ; Ittyerah, Ranjit ; Trotman, Winifred ; Chung, Eunice ; Sadaghiani, Shokufeh ; Prabhakaran, Karthik and Bedard, Madigan L , et al. (2025) In Hippocampus 35(5).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Aged, Female, Male, Magnetic Resonance Imaging/methods, Temporal Lobe/diagnostic imaging, Middle Aged, Aged, 80 and over, Neurodegenerative Diseases/diagnostic imaging, Image Processing, Computer-Assisted/methods, Alzheimer Disease/pathology
in
Hippocampus
volume
35
issue
5
article number
e70027
publisher
Wiley-Liss Inc.
external identifiers
  • pmid:40734544
  • scopus:105012102066
ISSN
1050-9631
DOI
10.1002/hipo.70027
language
English
LU publication?
yes
additional info
© 2025 Wiley Periodicals LLC.
id
00defb92-7e7e-4ed1-a4e4-23193ea75055
date added to LUP
2025-08-04 07:37:55
date last changed
2025-08-21 05:18:27
@article{00defb92-7e7e-4ed1-a4e4-23193ea75055,
  abstract     = {{<p>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.</p>}},
  author       = {{Sadeghpour, Niyousha and Lim, Sydney A and Wuestefeld, Anika and Denning, Amanda E and Ittyerah, Ranjit and Trotman, Winifred and Chung, Eunice and Sadaghiani, Shokufeh and Prabhakaran, Karthik and Bedard, Madigan L and Ohm, Daniel T and Artacho-Pérula, Emilio and de Onzoño Martin, Maria Mercedes Iñiguez and Muñoz, Monica and Romero, Francisco Javier Molina and González, José Carlos Delgado and Del Arroyo Jiménez, María and Del Marcos Rabal, Maria and Insausti Serrano, Ana María and González, Noemí Vilaseca and Sánchez, Sandra Cebada and de la Rosa Prieto, Carlos and Insausti, Ricardo and McMillan, Corey and Lee, Edward B and Detre, John A and Das, Sandhitsu R and Xie, Long and Tisdall, M Dylan and Irwin, David J and Wolk, David A and Yushkevich, Paul A and Wisse, Laura E M}},
  issn         = {{1050-9631}},
  keywords     = {{Humans; Aged; Female; Male; Magnetic Resonance Imaging/methods; Temporal Lobe/diagnostic imaging; Middle Aged; Aged, 80 and over; Neurodegenerative Diseases/diagnostic imaging; Image Processing, Computer-Assisted/methods; Alzheimer Disease/pathology}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Wiley-Liss Inc.}},
  series       = {{Hippocampus}},
  title        = {{Developing an Anatomically Valid Segmentation Protocol for Anterior Regions of the Medial Temporal Lobe for Neurodegenerative Diseases}},
  url          = {{http://dx.doi.org/10.1002/hipo.70027}},
  doi          = {{10.1002/hipo.70027}},
  volume       = {{35}},
  year         = {{2025}},
}