Single Cell Imaging of the Heart

心脏的单细胞成像

基本信息

批准号：
9049540
负责人：
RALPH WEISSLEDER, MD, PHD
金额：
$ 43.45万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-15 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9049540
关键词：
Algorithms BODIPY Biological Biological Models Biology Biosensor Cardiac Cardiac Myocytes Cardiotoxicity Cell model Cell physiology Cells Cereals Clinical Complex Computing Methodologies Cyclosporine Data Dimensions Drug Kinetics Drug effect disorder Fluorochrome Four-dimensional Goals Healed Health Heart Heart Diseases Hour Image Image Analysis Imaging technology Immune response In Vitro Individual Infarction Injectable Injury Intervention Ischemia Label Link Magnetic Resonance Imaging Maps Measurable Measurement Measures Membrane Potentials Methods Mitochondria Modeling Molecular Analysis Myocardial Ischemia Natural regeneration Nature Organ Organism Pharmaceutical Preparations Pharmacodynamics Physiological Physiology Preparation Protocols documentation Reporter Resolution Science Structure Techniques Testing Therapeutic Effect Therapeutic Intervention Three-Dimensional Image Time Tissue imaging Tissues Toxic effect Treatment Failure Treatment Protocols Ultrasonography Workload analog base cardiac pacing cardiovascular visualization cellular imaging chemotherapy clinically relevant data modeling drug distribution falls healing heart imaging image reconstruction improved in vitro Model in vivo in vivo imaging inhibitor/antagonist insight mathematical model microscopic imaging new technology novel novel strategies novel therapeutics pharmacodynamic model repaired respiratory response response biomarker sensor tool

项目摘要

DESCRIPTION (provided by applicant): Much of our current understanding of cardiac biology and function is derived from isolated heart preparations, whole organ level imaging, in vitro model systems and/or static endpoint analyses. In order to uncover fundamental biological principles and ultimately improve the treatment of cardiac diseases, new approaches for in vivo cellular level imaging in the beating heart are needed. We have recently developed such new technology (Nature Commun 2012;3:1054) employing a unique stabilizer setup, gating algorithm and new imaging reporters. This technological advance has allowed us to quantitate the contractile cycle of single cardiomyocytes, recruitment of host cells during complex healing mechanism following infarction (Nature 2012;487:325-9; Science 2013;339, 161-6) and drug action at the single cell level (Nature Commun 2013;4:1504). The goal of this application is to advance this cutting-edge in vivo imaging technology and to apply it to quantitative measurements of pharmacological intervention in the heart. Namely, we will develop and validate cardiac response markers, synthesize and test putative cardioprotective drugs and develop quantitative algorithms for image analysis. We anticipate that the new technology will have considerable applications in expanding our understanding of cardiac biology, and ultimately clinically translatable therapeutic intervention.

描述（由申请人提供）：我们当前对心脏生物学和功能的大部分理解来自孤立的心脏制剂，整个器官水平成像，体外模型系统和/或静态端点分析。为了发现基本的生物学原理并最终改善了心脏病的治疗方法，需要在跳动心脏中进行体内细胞水平成像的新方法。我们最近采用了独特的稳定器设置，门控算法和新成像记者开发了这种新技术（Nature Commun 2012; 3：1054）。这一技术进步使我们能够定量单个心肌细胞的收缩周期，在梗塞后复杂的愈合机制中募集宿主细胞的募集（Nature 2012; 487：325-9; Science 2013; 339，161-6）以及在单细胞水平上的药物作用（Nature Commun Commun Commun 2013; 4：1504）。该应用的目的是推进这种尖端的体内成像技术，并将其应用于心脏中药理干预的定量测量。也就是说，我们将开发和验证心脏反应标记，合成和测试推定的心脏保护药物，并开发用于图像分析的定量算法。我们预计，这项新技术将在扩展我们对心脏生物学的理解以及最终在临床上可以翻译的治疗干预措施方面具有相当大的应用。