Fourier Light-Field Interrogation of Congenital Heart Disease in vivo

先天性心脏病体内傅立叶光场询问

• 批准号: 2225990
• 负责人: Shu Jia
• 金额: $ 60万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2225990&HistoricalAwards=false
• 关键词: Fourier; Light; Field; Interrogation; Congenital

Congenital heart diseases (CHDs) are the most common type of birth defect and impact about 1% of the population worldwide. Hypoplastic left heart syndrome (HLHS) is the most dangerous form and the most common cause of death in infants with CHDs. Improved imaging technologies are needed to understand HLHS mechanisms and better achieve early diagnosis and intervention. This project will develop a novel light-field imaging method capable of assessing heart size, structure, and function in living animal models of HLHS. Results obtained leveraging this method are expected to reveal the pathways leading to HLHS and ultimately advance biotechnology for the benefit of patients with heart disease. To broaden the educational impacts of the work, the investigators will (1) prioritize and recruit women and minority undergraduate and graduate students to work on this project through on-campus or online resources, (2) integrate research and education by organizing an Atlanta international school on biophotonics and advanced optical microscopy, (3) develop innovative teaching and learning methods to enhance problem-based education and improve the public scientific literacy, and (4) engage underrepresented and veteran groups in STEM by enhancing school-lab interactions and through a summer camp on biophotonics. These efforts will impact the training of next-generation imaging engineers and professionals and promote the cross-fertilization of research and education from diverse disciplines.The goal of this project is to develop and deploy an integrative light-field functional screen platform, termed instant multi-color Fourier light-field microscopy (iFLFM), for simultaneous, all-optical assessment of heart morphology and function in order to identify causal genes of heart disease. The iFLFM system will be applied to monitor, in vivo, HLHS development in novel frog models of the disease. The Research Plan is developed under three aims: (1) Design, construct, and validate iFLFM to enable fast, volumetric, and simultaneous multi-color structural and dynamic imaging at the tissue and organ levels, which will form for basis for the instrumental platform for the proposed interrogation of embryonic frog hearts in vivo; (2) Validate iFLFM for in vivo observation of cardiac morphology and functions using control and Ets1-knockdown frog embryos, which will enable snapshot 3D and multi-parametric assessment and documentation of cardiac conditions and defects, confirm the influence of Ets1 as a causal gene for HLHS, and ready the basic architecture, assays, and processing for the proposed functional screen of other candidate genes; and (3) Advance the iFLFM platform for the functional screen of mutant embryonic frog hearts to identify causal genes for HLHS, which will reveal and document anatomical and functional variations and defects upon genetic mutations and identify mutations that lead to HLHS-like phenotype.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

先天性心脏病（CHD）是最常见的出生缺陷类型，影响全球约1%的人口。左心发育不良综合征（HLHS）是最危险的形式，也是婴儿CHD最常见的死亡原因。需要改进的成像技术来了解HLHS机制，更好地实现早期诊断和干预。该项目将开发一种新的光场成像方法，能够评估HLHS活体动物模型的心脏大小，结构和功能。利用这种方法获得的结果有望揭示导致HLHS的途径，并最终推进生物技术，使心脏病患者受益。为了扩大这项工作的教育影响，研究人员将（1）优先考虑并招募女性和少数民族本科生和研究生通过校园或在线资源参与该项目，（2）通过组织亚特兰大国际学校来整合研究和教育生物光子学和先进光学显微镜，（三）发展创新的教与学方法，加强以问题为本的教育，提高公众的科学素养，以及（4）通过加强学校与实验室的互动和生物光子学夏令营，让STEM中代表性不足的群体和退伍军人群体参与进来。这些努力将影响下一代成像工程师和专业人员的培训，并促进来自不同学科的研究和教育的交叉施肥。该项目的目标是开发和部署一个集成的光场功能屏幕平台，称为即时多色傅立叶光场显微镜（iFLFM），心脏形态和功能的全光学评估，以确定心脏病的致病基因。iFLFM系统将被应用于监测，在体内，HLHS的发展，在新的青蛙模型的疾病。本研究计划主要有三个目标：（1）设计、构建和验证iFLFM，使其能够在组织和器官水平上实现快速、立体和同步的多色结构和动态成像，这将为拟议的青蛙胚胎心脏活体询问的仪器平台奠定基础;（2）使用对照和Ets 1敲除的青蛙胚胎进行心脏形态和功能的体内观察，这将使得能够对心脏状况和缺陷进行快照3D和多参数评估和记录，确定Ets 1作为HLHS致病基因的影响，并为其他候选基因的功能筛选做好基础结构、检测和处理准备;以及（3）推进iFLFM平台用于突变胚胎蛙心的功能筛选，以鉴定HLHS的致病基因，这将揭示和记录基因突变后的解剖和功能变异和缺陷，并识别导致HLHS的突变-该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。