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

构建经过病理学验证的阿尔茨海默病神经影像工具

基本信息

批准号：
10390478
负责人：
Jean Augustinack
金额：
$ 47.25万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10390478
关键词：
Aging Alzheimer&apos s Disease Anatomy Atlases Autopsy Behavioral Biological Biological Markers Cell Death Clinical Clinical Research Computer software Data Data Set Dementia Diagnosis Diagnostic tests Disease Early Diagnosis Encapsulated Ensure Evaluation Future Genetic Genotype Goals Histologic Histology Human Image Intervention Label Lipofuscin Magnetic Resonance Imaging Manuals Maps Measures Memory Memory impairment Methods Modeling Motion Neurofibrillary Tangles Neurons Oligodendroglia Participant Pathogenesis Pathologic Pathology Population Positron-Emission Tomography Property ROC Curve Research Personnel Resolution Role Senile Plaques Sensitivity and Specificity Silver Staining Specific qualifier value Specificity Staging Structure Symptoms Testing Therapeutic Intervention Tissues Validation Work aging brain apolipoprotein E-4 cohort contrast imaging density early detection biomarkers entorhinal cortex ex vivo imaging healthy aging high risk histological stains hyperphosphorylated tau imaging biomarker improved in vivo neuroimaging novel pre-clinical quantitative imaging resilience specific biomarkers tau Proteins tau-1 tool ultra high resolution

项目摘要

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.

内嗅皮层是阿尔茨海默病的发病中心。这是早期皮质神经元缠结--过度磷酸化的tau蛋白--出现，最终导致细胞死亡。一旦tau病理学超过EC中的健康神经元，从健康衰老到痴呆的进展成为不可避免的。然而，尽管内嗅皮层在引发记忆障碍中起主要作用，内嗅皮层的生物标志物是大的和一维的替代物，其不能解释内嗅皮层的生物标志物。最早的tau病理在这个关键的结构。某些欧共体次区域（即ELr）受到严重打击，神经纤维缠结，即使在轻微的情况下，和其他洞穴晚得多。准确的，组织病理学- 内嗅皮层的有效成像生物标志物是识别关键的关键步骤， AD发病机制和开发新的临床干预措施来阻止AD进展。该项目的目标是为FreeSurfer生成内嗅子区域分割，作为这样一种生物标志物。这将通过多项高分辨率组织病理学定义标准，并适用于其他体内数据集。目前，没有任何包裹软件将内嗅包裹和死后成像提供了良好的分辨率，并允许直接病理学的验证。目的1是开发一种新的神经成像工具，分割八个EC FreeSurfer中的子区域。目的2是在相同病例中验证组织学中的EC亚区，建立神经元和病理学图谱。目标3是将EC子区域分割工具应用于在3 T和7 T下，在现有结构图像中的体内对照、MCI和AD受试者，描述了生物标志物。将新分割与现有生物标志物进行比较将确保特异性、灵敏度和可靠性。我们还将获得一种新型的高分辨率650 µm各向同性健康体内受试者的MRI数据集，以推动临床研究的上级分辨率。的目的是开发一种病理学验证的工具，为临床研究人员提供将行为和临床测量的定量成像。其他体内队列的未来应用将改变从健康老龄化到痴呆症进展的具体特征，既提高了我们检测AD的准确性，也提高了对AD的生物学理解。疾病的病理影响，这将是至关重要的发展治疗干预措施。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Quantitative and histologically validated measures of the entorhinal subfields in ex vivo MRI.

DOI：
10.1093/braincomms/fcac074
发表时间：
2022
期刊：
Brain communications
影响因子：
4.8
作者：
通讯作者：

The prosubiculum in the human hippocampus: A rostrocaudal, feature-driven, and systematic approach.

人类海马体中的前臂：一种特征驱动的、系统性的吻尾方法。

DOI：
10.1002/cne.25604
发表时间：
2024
期刊：
The Journal of comparative neurology
影响因子：
0
作者：
Rosenblum,EmmaW;Williams,EmilyM;Champion,SamanthaN;Frosch,MatthewP;Augustinack,JeanC
通讯作者：
Augustinack,JeanC

Stereology neuron counts correlate with deep learning estimates in the human hippocampal subregions.

DOI：
10.1038/s41598-023-32903-y
发表时间：
2023-04-11
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Oltmer, Jan;Rosenblum, Emma W. W.;Williams, Emily M. M.;Roy, Jessica;Llamas-Rodriguez, Josue;Perosa, Valentina;Champion, Samantha N. N.;Frosch, Matthew P. P.;Augustinack, Jean C. C.
通讯作者：
Augustinack, Jean C. C.

Pentad: A reproducible cytoarchitectonic protocol and its application to parcellation of the human hippocampus.