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

海马和内侧颞叶（MTL）的海马旁区由以下组成： 在解剖学和功能上不同的亚区，其被不同的病理学选择性靶向， 神经退行性疾病，如阿尔茨海默氏病（AD）和语义变异过程 进行性失语症（svPPA）。在AD中，研究MTL亚区的体内MRI研究经常显示 与死后病理学研究不一致的混合结果。这些不一致可能导致 MTL分割方法缺乏有效性和标准化。在svPPA中，MTL子区域是 受影响严重，自动化工具无法准确划分次区域。足够的空间分辨率 的成像体素，以可视化的内部MTL结构和标志，这是关键的有效 分区域划分。虽然在全球范围内收集了超过15，000个高分辨率扫描， MTL分区域分割协议之间缺乏标准化仍然是一个重大障碍。 在现有的分割协议中，MTL次区域边界的定义存在差异， 导致了实地调查结果的矛盾这项建议旨在加快我们的进展， 组，海马子域组，并完成我们的标准化，有效，可靠的协调 在高分辨率MRI扫描中分割MTL子区域的协议。我们将利用我们正在进行的， 成功的努力，并评估所提出的协调协议在扫描多中心数据集。在Aim中 1，我们将最终确定我们的协调分割协议，该协议是a）基于大型组织学数据集， 与神经解剖学家合作开发，B）由更大的社区评估以达成共识，c） 测试可靠性，以及d）在现有的自动化软件程序中实现。在目标2中，我们将验证 通过与特定病理学标志物的关联，在早期AD中的协调方案： MTL亚区萎缩率与PET测量之间相关性的解剖学特异性 轻度认知障碍和脑卒中患者MTL tau病理学和心血管风险标志物 β-淀粉样蛋白在目标3中，我们将通过以下方式进一步评估协调协议在svPPA中的有效性和实用性： 使用HSG协议对MTL子区域进行手动分割，并测试解剖结构 体积萎缩的特异性。在目标4中，我们将通过提供培训和 教育材料，人工和自动细分的现场研讨会，并取得成果 公开的措施。我们的有效，可靠和可重复的MTL子区域分割协议 将使世界各地的团体受益，这些团体已经并将继续收集数千个高分辨率数据，以研究 各种神经和精神疾病。这也为未来研究如何区分 MTL亚区域的疾病过程可能导致特定认知功能的损伤。我们 协调过程可以适于实现针对其他大脑区域的有效的、协调的分割。

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 how distinct disease processes in the MTL subregions may lead to impairments in specific cognitive functions. Our harmonization process can be adapted for achieving valid, harmonized segmentation for other brain regions.