Single Cell Imaging of the Heart

心脏的单细胞成像

• 批准号: 9265709
• 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
• 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/9265709
• 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 Modelings; Drug effect disorder; Fluorochrome; Four-dimensional; Goals; 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; Myocardial Ischemia; Natural regeneration; Nature; Organ; Organism; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Physiological; Physiology; Preparation; Protocols documentation; Recruitment Activity; Reporter; Resolution; Science; Structure; Techniques; Testing; Therapeutic Effect; Therapeutic Intervention; Three-Dimensional Image; Time; Tissue imaging; Toxic effect; Treatment Failure; Treatment Protocols; Ultrasonography; Workload; analog; base; cardiac pacing; cardiovascular visualization; cellular imaging; chemotherapy; clinically relevant; clinically translatable; data modeling; drug distribution; falls; healing; heart imaging; image reconstruction; improved; in vitro Model; in vivo; in vivo imaging; inhibitor/antagonist; insight; intravital imaging; mathematical model; microscopic imaging; molecular imaging; new technology; novel; novel strategies; novel therapeutics; public health relevance; repaired; response; response biomarker; sensor; tool

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(申请人提供)：我们目前对心脏生物学和功能的大部分了解来自于离体心准备、全器官水平成像、体外模型系统和/或静态终点分析。为了揭示基本的生物学原理并最终改进心脏疾病的治疗，需要在跳动的心脏中进行活体细胞水平成像的新方法。我们最近开发了这样的新技术(自然通讯2012；3：1054)，采用了独特的稳定器设置、门控算法和新的成像记者。这一技术进步使我们能够量化单个心肌细胞的收缩周期、梗死后复杂愈合机制中宿主细胞的招募(Nature 2012；487：325-9；Science 2013；339,161-6)以及单细胞水平的药物作用(Nature Commun 2013；4：1504)。这项应用的目标是推进这一尖端的活体成像技术，并将其应用于心脏药物干预的定量测量。也就是说，我们将开发和验证心脏反应标记物，合成和测试假定的心脏保护药物，并开发用于图像分析的定量算法。我们预计，这项新技术将在扩大我们对心脏生物学的理解方面有相当大的应用，并最终在临床上可翻译的治疗干预。

项目成果

Design of a Microfluidic Chip for Magnetic-Activated Sorting of One-Bead-One-Compound Libraries.

用于一珠一化合物文库磁激活分选的微流控芯片的设计。

• DOI: 10.1021/acscombsci.5b00180
• 发表时间: 2016
• 期刊: ACS combinatorial science
• 作者: Cho,Choi-Fong;Lee,Kyungheon;Speranza,Maria-Carmela;Bononi,FernandaC;Viapiano,MarianoS;Luyt,LeonardG;Weissleder,Ralph;Chiocca,EAntonio;Lee,Hakho;Lawler,SeanE
• 通讯作者: Lawler,SeanE