Neuroimaging and Vascular Core

神经影像和血管核心

• 批准号: 10708163
• 负责人: ANDRE OBENAUS
• 金额: $ 86.74万
• 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/10708163
• 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; Collaborations; 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; Individual; International; Knowledge Portal; Label; Lead; Link; Literature; Magnetic Resonance Imaging; Mainstreaming; Maps; Measures; Metabolic; Modeling; Monitor; Mouse Strains; Multiomic Data; Mus; Nature; Neurobiology; Onset of illness; Paint; Pathology; Perfusion; Phenotype; Physiological; Postdoctoral Fellow; Predisposition; RNA; Reproducibility; Research; Research Personnel; Rest; Rodent Model; Scanning; Sex Differences; Standardization; Structure; Students; Techniques; Tissues; Translating; age group; base; biomarker development; biomarker identification; biomarker signature; clinical diagnosis; clinically relevant; computerized data processing; data management; efficacy evaluation; functional genomics; human disease; human model; imaging approach; 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 阿尔茨海默病 (AD) 受试者的临床神经影像学是了解疾病发作的一个重要方面， UCI MODEL-AD 团队正在开发新的 AD 小鼠模型。 随着疾病模型产生新的小鼠模型，可以更容易地重现人类疾病。 开发和表型项目（DMP）、神经影像和神经血管核心（NIVC）将承担 使用临床相关的磁力对这些小鼠进行深入表型的成像方式概要 磁共振成像 (MRI) 序列可探测某个年龄的结构、组织细胞结构和生理功能， NIVC 还将采用一种新颖的容器涂漆方法来标记性别和饮食依赖方式。 NIVC 的目标是显着增强我们的结构和功能。 了解 MODEL AD 小鼠大脑如何响应类似于人类 AD 的遗传扰动 并将这些发现与临床 AD 成像联系起来。为了实现这些目标，我们将实现四个目标。 目标 1 是确定 DMP 基础平台小鼠和高兴趣模型的深层 MRI 和血管表型。 该目标将使用标准化（阿尔茨海默病神经影像计划；ADNI 衍生）和创新 多模态 MRI 技术描述结构、血管、结构/功能连接和代谢 目标 2 是通过将 MRI 与 MRI 相结合来促进生物标志物的开发。 此处，NIVC 数据将与 DMP 和功能基因组学合并。 生物信息学数据管理核心 (FGBDMC) 数据，用于识别神经影像数据上的生物标志物签名 目标 3 将提供有关 AD 神经生物学基础的见解，将验证新兴的潜在生物标志物 MRI。 来自最近的人类 AD 研究，其中包括光谱成像和定量磁化率绘图。 目标 4 是将 MODEL-AD 神经影像和血管研究结果传播到更大的国际 AD NIVC 将：1）创新。 用于小鼠模型表型分析的新成像方法，并将这些数据公开用于 AD 研究人员，2) 与人类和小鼠神经影像小组合作，对潜力进行评估 可以指导 AD 早期临床诊断的预测标记，3) 教育科学界人士（学生、博士后、 新研究人员）和更广泛的关于 AD 的公共社区，以及 4）转化 NIVC 的研究结果以提供 神经影像学方法帮助诊断和监测人类 AD 治疗反应的新方向。