Building a pathology-validated neuroimaging tool for Alzheimer's Disease

内嗅皮层是阿尔茨海默病的起点。这就是早期皮质神经原纤维 缠结-过度磷酸化的tau-出现，最终导致细胞死亡。曾经的陶氏病理 超过EC中的健康神经元，从健康衰老到痴呆的进展是不可避免的。 然而，尽管内嗅皮层启动记忆损伤的主要作用，目前的成像 内嗅皮层的生物标志物是大的一维替代物，无法解释 这一关键结构中最早的tau病理。某些欧共体次区域(即ELR)受到 神经原纤维缠绕，即使在轻度病例中也是如此，其他病例则在很长时间后才塌陷。准确的，组织病理学上的- 经过验证的内嗅觉皮质成像生物标志物是识别关键的关键步骤 阿尔茨海默病的发病机制和开发新的临床干预措施来阻止AD的进展。 这个项目的目标是生成一个内嗅子区域分割，用于自由浏览 作为这样的生物标记物。这将在组织病理学上以高分辨率由多个 标准，并适用于其他体内数据集。目前，还没有分割软件细分和 内嗅觉分离和尸检成像提供了极好的分辨率，并允许直接 病理上的确认。目标1是开发一种新的神经成像工具来分割八个EC 自由冲浪中的子区域。目标2是在相同的病例中验证EC亚区的组织学和 建立神经和病理档案。目标3是将欧共体分区工具应用于In 在3T和7T的现有结构图像中测试VIVO对照、MCI和AD受试者 描述的生物标志物。将新的分段与现有的生物标记物进行比较将确保 体内试验的特异性、敏感性和可靠性。我们还将获得一种新的高分辨率650微米各向同性 健康活体受试者的MRI数据集，推动临床研究的优越分辨率。这个 AIMS开发了一种经过病理验证的工具，将为临床研究人员提供联系的能力 行为和临床测量的定量成像。未来对其他活体队列的应用 将改变从健康老龄化到痴呆症进展的具体特征，提供 这既提高了我们检测AD的能力的准确性，也改善了对AD的生物学理解 疾病的病理影响，这将是制定治疗干预措施的关键。

Entorhinal cortex is ground zero for Alzheimer’s disease. This is where the early cortical neurofibrillary tangles – hyperphosphorylated tau – appear, which ultimately leads to cell death. Once tau pathology exceeds healthy neurons in EC, the progression from healthy aging to dementia becomes inevitable. However, despite the primary role of entorhinal cortex initiating memory impairment, current imaging biomarkers of entorhinal cortex are large and unidimensional surrogates that fail to account for the earliest tau pathology within this critical structure. Certain EC subregions (i.e. ELr) are hit hard by neurofibrillary tangles, even in mild cases and others cave much later. An accurate, histopathologically- validated imaging biomarker of the entorhinal cortex is an essential step towards identifying key mechanisms of AD pathogenesis and developing novel clinical interventions to stop AD progression. The objective of this project is to generate an entorhinal subregions segmentation for FreeSurfer to serve as such a biomarker. This will be histopathologically-defined at a high resolution by multiple criteria and applicable to other in vivo datasets. Currently, no parcellation software segments an entorhinal parcellation and post mortem imaging affords excellent resolution and allows for direct validation of the pathology. Aim 1 is to develop a novel neuroimaging tool that segments the eight EC subregions in FreeSurfer. Aim 2 is to validate the EC subregions in histology in same cases and establish neuronal and pathology profiles. Aim 3 is to apply the EC subregion segmentation tool to in vivo controls, MCI, and AD subjects in existing structural images at 3T and 7T to test against previously described biomarkers. Comparing the new segmentation against existing biomarkers will ensure specificity, sensitivity and reliability in vivo. We will also acquire a novel high resolution 650 µm isotropic MRI dataset in healthy in vivo subjects to push forward a superior resolution for clinical research. The aims develop a pathologically validated tool that will provide clinical researchers the ability to relate quantitative imaging with behavioral and clinical measures. Future application to other in vivo cohorts will transform the specific characterization of the progression from healthy aging to dementia, providing both increased accuracy in our ability to detect AD, as well as improved biological understanding of the pathological effects of the disease that will be critical in developing therapeutic interventions.