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

内侧颞叶(MTL)的海马区和海马区由 在解剖和功能上不同的亚区被不同的病理组织选择性靶向 神经退行性疾病的过程，如阿尔茨海默病(AD)和语义变异初级 进行性失语(SvPPA)。在AD中，研究MTL亚区的活体MRI研究经常显示 与尸检病理研究不一致的混合发现。这些不一致可能导致 从MTL分割方法缺乏有效性和规范性出发。在svPPA中，MTL亚区为 受严重影响，自动化工具无法准确分割子区域。足够的空间分辨率 需要成像体素来可视化内部MTL结构和地标，这对于有效 子区域的分割。虽然全世界已经收集了超过15,000张高分辨率扫描， MTL次区域分割协议之间缺乏标准化仍然是一个重大障碍。 现有分段议定书之间MTL次区域边界定义的可变性有 导致了该领域相互矛盾的发现。这项建议旨在加快我们的进展 海马子场组，并完成我们标准化、有效和可靠的协调 用于高分辨率MRI扫描中MTL亚区分割的协议。我们将利用我们正在进行的 成功的努力，并在多中心数据集的扫描中评价拟议的统一议定书。在AIM 1，我们将最终确定我们的协调分割协议，即a)基于大型组织学数据集和 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) 对可靠性进行测试，以及d)在现有自动化软件程序中实现。在目标2中，我们将验证 通过与特定病理标记物的关联在早期AD中的协调方案：a)检测 跨MTL亚区萎缩率与PET测量结果之间关系的解剖学特异度 轻度认知障碍和脑部疾病患者MTL tau的病理学和心血管风险标记物 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svPPA中协调议定书的有效性和实用性 使用HSG协议执行MTL亚区的手动分割并测试解剖 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、用于手动和自动分类并取得成果的面对面研讨会 可公开使用的措施。我们的有效、可靠和可重复性的MTL亚区分割协议 将使世界各地拥有并继续收集数千个高分辨率数据来研究 各种神经和精神疾病。这也为未来研究如何区分 MTL亚区的疾病过程可能会导致特定认知功能的损害。我们的 可以采用协调过程来实现对其他大脑区域的有效、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.