Sadeghpour Niyousha, Lim Sydney A, Wuestefeld Anika, Denning Amanda E, Ittyerah Ranjit, Trotman Winifred, Chung Eunice, Sadaghiani Shokufeh, Prabhakaran Karthik, Bedard Madigan L, Ohm Daniel T, Artacho-Pérula Emilio, de Onzoño Martin Maria Mercedes Iñiguez, Muñoz Monica, Romero Francisco Javier Molina, González José Carlos Delgado, Del Arroyo Jiménez María, Del Marcos Rabal Maria, Insausti Serrano Ana María, González Noemí Vilaseca, Sánchez Sandra Cebada, de la Rosa Prieto Carlos, Insausti Ricardo, McMillan Corey, Lee Edward B, Detre John A, Das Sandhitsu R, Xie Long, Tisdall M Dylan, Irwin David J, Wolk David A, Yushkevich Paul A, Wisse Laura E M
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Hippocampus. 2025 Sep;35(5):e70027. doi: 10.1002/hipo.70027.
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.
内侧颞叶（MTL）的前部是散发性阿尔茨海默病（AD）和边缘型为主的年龄相关性TDP-43脑病（LATE）中病理学最早靶向的区域之一，这表明该区域的指标有潜力作为成像生物标志物。利用一个独特的包含组织学和磁共振成像（MRI）扫描的尸检数据集，我们旨在：（1）为体内3T MRI开发一种解剖学上有效的内嗅皮质（ERC）、布罗德曼区（BA）35和BA36的分割方案；（2）将该方案纳入一种自动化方法中。我们纳入了20例病例（年龄61 - 97岁，50%为女性），有和没有神经退行性疾病（分别为11例和9例），以确保所开发方案的通用性。对这些病例的数字化MTL尼氏染色冠状组织学切片进行标注，并与同一受试者的尸检MRI进行配准。通过确定MTL皮质的组织学边界相对于解剖标志的位置来开发该方案。随后，该方案对15例病例进行了两次应用，间隔为2周，以使用骰子相似性指数（DSI）评估评分者内信度。此后，将其应用于我们内部的海马亚区自动分割（ASHS）-T1方法中，并使用DSI进行评估。针对各种解剖标志评估了ERC、BA35和BA36的前部组织学边界距离，并选择了相对于海马起始处的距离。为了制定分割规则，我们检查了组织学切片中边界相对于冠状切片中解剖标志的位置。评分者内信度的MTL前部皮质的DSI为0.85 - 0.88，ASHS-T1相对于手动分割的DSI为0.62 - 0.65。我们开发了一种可靠的分割方案，并将其纳入一种自动化方法中。鉴于MTL前部皮质在AD和LATE中对tau沉积的易感性，预期更新后的方法将改善这些疾病的成像生物标志物。
