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

协调一致的内侧颞叶亚区域分割协议：痴呆症研究的基本要素

• 批准号: 10574500
• 负责人: Rosanna Kathleen Olsen
• 金额: $ 69.22万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574500
• 关键词: Acceleration; Address; Adoption; Affect; Alzheimer' s Disease; Amyloid beta-Protein; Anatomy; Atlases; Atrophic; Autopsy; Biological Markers; Brain region; Brodmann' s area; Cardiovascular Diseases; Cerebrum; Clinical; Cognitive Science; Collaborations; Communities; Computer software; Consensus; Data; Data Set; Dementia; Development; Disease; Educational Materials; Educational workshop; Elements; Failure; Foundations; Funding; Goals; Hippocampus; Histology; Image; Impairment; International; Internet; MRI Scans; Magnetic Resonance Imaging; Manuals; Masks; Measurement; Measures; Medial; Mental disorders; Methods; Neurodegenerative Disorders; Neurologic; Outcome Measure; Pathologic; Pathologic Processes; Pathology; Patients; Persons; Population; Positron-Emission Tomography; Primary Progressive Aphasia; Procedures; Process; Protocols documentation; Reporting; Reproducibility; Research; Resolution; Risk; Role; Scanning; Semantics; Specificity; Standardization; Structure; Temporal Lobe; Testing; Training; Training and Education; Variant; Visualization; Volunteer Organization; Work; automated segmentation; biomarker development; cardiovascular risk factor; cognitive function; comparison control; entorhinal cortex; improved; in vivo; member; mild cognitive impairment; nervous system disorder; neuroimaging; neuropathology; programs; tau Proteins; tool

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.

内侧颞叶 (MTL) 的海马和海马旁区域由 解剖学和功能上不同的亚区域，不同的病理有选择地针对 神经退行性疾病的过程，例如阿尔茨海默病 (AD) 和语义变异 进行性失语症（svPPA）。在 AD 中，调查 MTL 亚区域的体内 MRI 研究经常表明 与尸检病理学研究不一致的混合结果。这些不一致可能会导致 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 需要大量的成像体素来可视化内部 MTL 结构和地标，这对于有效的 次区域的划分。虽然在全球范围内收集了超过 15,000 张高分辨率扫描图， MTL次区域分割协议之间缺乏标准化仍然是一个重大障碍。 现有分割协议之间 MTL 次区域边界定义的可变性 导致了该领域相互矛盾的发现。该提案旨在加快我们所取得的进展 组，海马子域组，并完成我们标准化、有效且可靠的协调 高分辨率 MRI 扫描中 MTL 子区域分割的协议。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估拟议的协调协议。瞄准 1，我们将最终确定我们的统一分割协议，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) 进行可靠性测试，以及 d) 在现有的自动化软件程序中实施。在目标 2 中，我们将验证 通过与特定病理标志物的关联来制定早期 AD 的统一方案：a) 测试 MTL 亚区域萎缩率与 PET 测量之间关联的解剖学特异性 轻度认知障碍和脑卒中患者的 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 svPPA 协调协议的有效性和实用性： 使用 HSG 协议对 MTL 子区域进行手动分割并进行解剖学测试 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、手动和自动分割的现场研讨会以及成果 措施公开。我们有效、可靠且可重复的 MTL 子区域分割协议 将使全世界已经并继续收集数千个高分辨率数据来研究的团体受益 各种神经和精神疾病。它还为未来的研究奠定了基础，以了解如何区分 MTL 亚区域的疾病过程可能会导致特定认知功能受损。我们的 可以调整协调过程以实现其他大脑区域的有效、协调的分割。