Fourier Light-Field Interrogation of Congenital Heart Disease in vivo

点击翻译按钮获取中文摘要

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.