Neuroimaging and Vascular Core

神经影像和血管核心

• 批准号: 10592222
• 负责人: ANDRE OBENAUS
• 金额: $ 88.49万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592222
• 关键词: 3-Dimensional; Age; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease model; Alzheimer’s disease biomarker; Animal Model; Bioinformatics; Biological Markers; Blood Vessels; Brain; Brain region; Cellularity; Cerebrovascular system; Clinical; Communities; Complex; Data; Data Set; Development; Diagnosis; Diet; Diffusion; Dimensions; Disease; Disease model; Educational workshop; Environmental Risk Factor; Evaluation; Exhibits; Functional Magnetic Resonance Imaging; Genetic; Genomics; Goals; Human; Image; Imaging Techniques; Individual; International; Knowledge Portal; Label; Lead; Link; Literature; Magnetic Resonance Imaging; Mainstreaming; Measures; Metabolic; Modeling; Monitor; Mouse Strains; Multiomic Data; Mus; Nature; Neurobiology; Onset of illness; Pathology; Perfusion; Phenotype; Physiological; Postdoctoral Fellow; Predisposition; RNA; Reproducibility; Research; Research Personnel; Rest; Rodent Model; Scanning; Sex Differences; Standardization; Structure; Students; Tissues; Translating; age group; base; biomarker development; biomarker signature; clinical diagnosis; clinically relevant; computerized data processing; data management; functional genomics; human disease; human model; imaging approach; imaging biomarker; imaging modality; innovation; insight; interest; magnetic resonance imaging biomarker; microbiome; model development; mouse model; multimodality; multiple omics; neuroimaging; neuroimaging marker; neurovascular; novel; predictive marker; programs; sex; spectroscopic imaging; symposium; treatment response

ABSTRACT Clinical neuroimaging of Alzheimer’s Disease (AD) subjects is a critical aspect of understanding disease onset, progression, and response to therapies. The UCI MODEL-AD team is developing new mouse models of AD that more readily recapitulate the human disease. As new mouse models are generated by the Disease Model Development and Phenotyping Project (DMP), the Neuroimaging and Neurovascular Core (NIVC) will undertake a compendium of imaging modalities to deeply phenotype these mice using clinically relevant, magnetic resonance imaging (MRI) sequences to probe structure, tissue cellularity, and physiological functions in an age, sex and diet dependent manner. The NIVC will also undertake a novel vessel-painting approach that labels the cerebrovasculature. The goals of the NIVC are to significantly increase our structural and functional understanding of how the MODEL AD mouse brain responds to genetic perturbations reminiscent of human AD and to link these discoveries to clinical AD imaging. To accomplish these goals, we will undertake four Aims. Aim 1 is to determine deep MRI and vascular phenotypes for DMP base-platform mice and high-interest models. This Aim will use standardized (Alzheimer’s Disease Neuroimaging Initiative; ADNI-derived) and innovative multimodal MRI techniques to describe structural, vascular, structural/functional connectivity, and metabolic signatures in emerging AD mouse models. Aim 2 is to facilitate biomarker development by integrating MRI with histopathological and multi-omic data. Here, NIVC data will be merged with DMP and Functional Genomics Bioinformatics Data Management Core (FGBDMC) data to identify biomarker signatures on neuroimaging data that provides insights on the underlying AD neurobiology. Aim 3 will validate potential MRI biomarkers emerging from recent human AD studies, which include spectroscopic imaging and quantitative susceptibility mapping. Aim 4 is to disseminate MODEL-AD neuroimaging and vascular findings to the larger international AD community and to provide entry to new researchers interested in AD. In summary, the NIVC will: 1) innovate new imaging approaches for phenotyping mouse models and make these data publicly available for AD researchers, 2) collaborate with human and mouse neuroimaging groups to pursue evaluation of potential predictive markers that could guide early clinical diagnosis of AD, 3) educate the scientific (students, postdocs, new researchers) and the broader public community about AD, and, 4) translate the NIVC findings to provide new directions for neuroimaging approaches to aid diagnosis and monitor treatment response of human AD.

抽象的 阿尔茨海默氏病（AD）受试者的临床神经影像学是了解疾病发作的关键方面， 进展和对疗法的反应。 UCI Model-AD团队正在开发新的AD鼠标模型 更容易概括人类疾病。由于疾病模型生成了新的小鼠模型 开发和表型项目（DMP），神经影像学和神经血管核心（NIVC）将进行 成像方式的汇编，以深层表型，使用临床相关的磁性 共振成像（MRI）序列，以探测一个年龄的探针结构，组织细胞和生理功能， 性别和饮食依赖的方式。 NIVC还将采用一种新型的船只拍印方法，将其标记为 脑血管管。 NIVC的目标是显着提高我们的结构和功能 了解模型AD小鼠脑对遗传扰动的反应如何让人联想到人类AD 并将这些发现与临床广告成像联系起来。为了实现这些目标，我们将实现四个目标。 目的1是确定DMP碱基平台小鼠和高息模型的深MRI和血管表型。 该目标将使用标准化（阿尔茨海默氏病神经影像倡议； ADNI衍生）和创新 多模式MRI技术来描述结构，血管，结构/功能连通性和代谢 新兴AD鼠标模型中的签名。目标2是通过将MRI与 组织病理学和多OMIC数据。在这里，NIVC数据将与DMP和功能基因组合并 生物信息学数据管理核心（FGBDMC）数据以识别有关神经影像学数据的生物标志物签名 这提供了有关基础AD神经生物学的见解。 AIM 3将验证潜在的MRI生物标志物出现 从最近的人类广告研究中，其中包括光谱成像和定量敏感性映射。 AIM 4是向更大的国际广告传播Model-AD神经影像学和血管发现 社区并为对AD感兴趣的新研究人员提供入门。总而言之，NIVC将：1）创新 表型鼠标模型的新成像方法，并使这些数据公开用于AD 研究人员，2）与人类和小鼠神经影像群合作，以追求潜在的评估 可以指导AD早期临床诊断的预测标记，3）教育科学（学生，博士后， 新研究人员）和广泛的公共社区，以及4）转换NIVC的发现以提供 神经影像学方法的新方向有助于诊断和监测人类AD的治疗反应。