Cardiac photon counting CT and its application in studying interactions between Alzheimer's and heart disease

心脏光子计数CT及其在研究阿尔茨海默病与心脏病相互作用中的应用

• 批准号: 10094804
• 负责人: CRISTIAN T BADEA
• 金额: $ 187.31万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10094804
• 关键词: 3-Dimensional; Address; Adoption; Affect; Aging; Algorithms; Alleles; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease risk; Animal Experiments; Animal Model; Apolipoprotein E; Arterial Fatty Streak; Atherosclerosis; Base of the Brain; Behavior; Behavior assessment; Biological Markers; Brain; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Characteristics; Clinical; Cognitive; Data; Development; Diet; Dimensions; Disease Marker; Dose; Environmental Impact; Epidemiology; Exercise; Exposure to; Fatty acid glycerol esters; Foundations; Generations; Genes; Genetic; Genetic Models; Genetic Risk; Genotype; Heart Diseases; Human; Image; Imaging Device; Immune response; Impaired cognition; Intervention; Link; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Methodology; Methods; Modeling; Monitor; Morphologic artifacts; Mouse Strains; Mus; Myocardial perfusion; NOS2A gene; Names; Nitric Oxide Synthase; Noise; Outcome; Oxidation-Reduction; Pathologic; Performance; Phenotype; Photons; Physiologic Monitoring; Pre-Clinical Model; Process; Protein Isoforms; Protocols documentation; Research; Resolution; Risk; Risk Factors; Role; Scanning; System; Technology; Testing; Time; X-Ray Computed Tomography; base; behavioral study; cardiac plaque; cardiovascular risk factor; combat; computerized data processing; data acquisition; deep learning; detector; environmental stressor; exercise intervention; exercise regimen; heart function; heart imaging; human subject; imaging modality; improved; in vivo; insight; learning strategy; magnetic resonance imaging biomarker; mouse model; non-invasive imaging; novel; photon-counting detector; pre-clinical; preclinical imaging; preclinical study; predictive modeling; prototype; reconstruction; resilience; response; sedentary lifestyle; simulation; spectral distortion; sugar; tool

PROJECT SUMMARY/ABSTRACT Aging is accompanied by increasing vulnerability to cardiovascular disease (CVD) and Alzheimer’s disease (AD). The ongoing rise in both AD and CVD has been ascribed to the increasing adoption of a Western sedentary lifestyle accompanied by a diet rich in fats and sugars. To understand the links between AD and CVD in human subjects, non-invasive imaging methods such X-ray computed tomography (CT) and magnetic resonance (MR) are essential. Cardiac CT is one of the most powerful applications of these methodologies at both clinical and preclinical levels, but it is currently limited by its low contrast resolution. Our primary objective in this proposal is to improve the current status of cardiac CT based on photon counting detector technology and demonstrate its capabilities in preclinical studies focused on studying the interaction between CVD and AD. Our central hypothesis is that cardiac photon counting CT will provide low dose spectral characterization of atherosclerotic plaques together with cardiac function, while enabling longitudinal monitoring of interventions such as exercise. We will pursue three specific aims. In specific aim 1, we will develop the theoretical foundation and GPU optimized tools for reconstruction of cardiac 5D (3D + Time + Energy) photon counting CT data. We will incorporate deep learning solutions to overcome fundamental barriers to the advancement of this technology: regularization to deal with image noise associated with photon binning, robust material decomposition to combat spectral distortion, and automated cardiac function and plaque analysis to handle data dimensionality. During the second specific aim, we will characterize the performance of our novel cardiac photon counting CT imaging using simulations, phantoms and animal experiments to show its benefits for atherosclerotic plaque characterization and cardiac function estimation. Finally, in specific aim 3 we will investigate if cardiovascular risk impacts brain phenotypes in animal models of genetic risk for AD. CVD and AD share a genetic link via the ApoE gene and its isomorphic allele 4 (APOE4). We will use APOE3/HN and APOE4/HN mouse strains that express the corresponding specific targeted-replacement human APOE allele, on a humanized Nitric Oxide Synthase 2 (denoted here as HN) background. Using these models, we will first assess the impact of a high fat, high sugar diet on cardiovascular phenotypes (atherosclerotic plaque size, numbers; cardiac function measured with CT) and how these genetic differences are reflected in behavior and brain MR based biomarkers compared with control mice in the same background. Finally, we will also investigate the potential to rescue these phenotypes using exercise as the intervention. The impact of the proposed research will validate the usage of photon counting CT technology to enhance routine cardiac CT imaging applications. Our project will enable new powerful integrative approaches to examine the impact of environmental stressors to alter APOE genotype- specific vulnerability, or resilience to CVD and AD.

项目总结/摘要 衰老伴随着对心血管疾病（CVD）和阿尔茨海默病（AD）的易感性增加。 AD和CVD的持续上升归因于越来越多的西方久坐不动的人 生活方式伴随着富含脂肪和糖的饮食。了解人类AD和CVD之间的联系 受试者，非侵入性成像方法，如X射线计算机断层扫描（CT）和磁共振（MR） 是必不可少的。心脏CT是这些方法在临床和医学上最有力的应用之一。 临床前水平，但目前受到其低对比度分辨率的限制。我们提出这个建议的主要目的 旨在改善基于光子计数探测器技术的心脏CT的现状， 其在临床前研究方面的能力主要集中在研究CVD和AD之间的相互作用。我们的中央 假设心脏光子计数CT将提供动脉粥样硬化低剂量光谱表征 斑块与心脏功能一起，同时能够纵向监测干预措施，如运动。 我们将追求三个具体目标。在具体目标1中，我们将开发理论基础和GPU 用于重建心脏5D（3D +时间+能量）光子计数CT数据的优化工具。我们将 结合深度学习解决方案，克服技术进步的根本障碍： 正则化处理图像噪声与光子面元相关，鲁棒的材料分解打击 频谱失真，以及自动心脏功能和斑块分析，以处理数据维度。期间 第二个具体目标，我们将描述我们的新型心脏光子计数CT成像的性能 通过模拟、实体模型和动物实验来显示其对动脉粥样硬化斑块的益处 表征和心脏功能估计。最后，在具体目标3中，我们将研究心血管 风险影响AD遗传风险动物模型中的大脑表型。CVD和AD通过以下途径共享遗传联系： ApoE基因及其同形等位基因4（APOE 4）。我们将使用APOE 3/HN和APOE 4/HN小鼠品系， 在人源化一氧化氮上表达相应的特异性靶向置换人APOE等位基因， 合成酶2（在此表示为HN）背景。使用这些模型，我们将首先评估高脂肪， 高糖饮食对心血管表型的影响（动脉粥样硬化斑块大小、数量;测量的心功能 以及这些遗传差异如何反映在行为和大脑MR生物标志物中， 在相同的背景下与对照小鼠进行比较。最后，我们还将研究拯救这些 使用运动作为干预的表型。拟议研究的影响将验证 光子计数CT技术增强常规心脏CT成像应用。我们的项目将使新的 强有力的综合方法来检查环境应激改变APOE基因型的影响- 具体的脆弱性，或对心血管疾病和AD的适应能力。