Single Cell Imaging of the Heart

描述（由申请人提供）：我们目前对心脏生物学和功能的理解大部分来自于分离的心脏制剂、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善心脏病的治疗，需要在跳动的心脏中进行体内细胞水平成像的新方法。我们最近开发了这样的新技术（Nature comm 2012;3:10 . 54），采用了独特的稳定器设置、门控算法和新的成像报告。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募集（Nature 2012;487:325-9; Science 2013; 339,161 -6）和单细胞水平的药物作用（Nature Commun 2013;4:1504）。本应用程序的目标是推进这种尖端的体内成像技术，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志物，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。

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.