3D Imaging of electrical activity in myocardial tissue

心肌组织电活动的 3D 成像

• 批准号: 6741448
• 负责人: Arkady M PERTSOV
• 金额: $ 55.43万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6741448
• 关键词: bioimaging /biomedical imaging; cardiac myocytes; fluorescent dye /probe; heart electrical activity; heart imaging /visualization /scanning; image enhancement; light scattering; mathematical model; myocardium; optical tomography; technology /technique development; three dimensional imaging /topography; ventricular fibrillation

DESCRIPTION (provided by applicant): Understanding the mechanisms that underlie abnormalities of electrical conduction in the heart is the key to the development of effective antiarrhythmic therapies. During the last decade, significant progress has been made in imaging electrical excitation waves in the heart using voltage-sensitive fluorescent dyes. However, until recently imaging using voltage-sensitive dyes was limited primarily to the epicardial surface. The goal of the proposed study is to develop a technology that would enable optical imaging of electrical excitation throughout the myocardial wall. Specifically, this technology should image the filaments, or organizing centers of vortex-like electrical activity. These are widely believed to be responsible for the initiation and maintenance of ventricular fibrillation, and the filaments are a key to their behavior. To address the technical challenges of this novel technology we propose a coordinated project involving the research groups of Dr. A. Pertsov (PI) from the Department of Pharmacology, SUNY Upstate Medical University, who pioneered the three-dimensional imaging of vortex-like excitation in chemical excitable systems and in the heart; Dr. D. Boas at the Harvard Medical School and the Massachusetts General Hospital NMR Center, an expert in optical tomography; Dr. L. Loew at the Center for Biomedical Imaging Technology, University of Connecticut Health Center (Co-PI), a leader in the development of voltage-sensitive probes and optical imaging; and the group of Dr. D. Weitz at the Department of Physics, Harvard University (Co-PI), renowned for their expertise in optical imaging and multiple-scattering media. The specific aims of the project are: 1) to create realistic computer models for reconstructing 2D optical images from 3D distributions of the transmembrane potential in myocardial tissue (forward problem), 2) to apply diffusive optical tomography to 3D reconstruction of the actual electrical activation in the heart (inverse problem); 3) to design, synthesize and test in myocardial tissues a family of near-infrared voltage-sensitive dyes optimized for 3D imaging of electrical activation in the heart; 4) to explore two-photon fluorescence and second-harmonic generation for 3D imaging of electrical activity in cardiac myocytes and tissues at subcellular and sub-millimeter scales. Successful completion of this project will break ground for a new technology, the 3D imaging of electrical activation in the heart.

描述（由申请人提供）：了解心脏电传导异常的机制是开发有效抗心律失常治疗的关键。在过去的十年中，在使用电压敏感荧光染料成像心脏中的电激发波方面取得了重大进展。然而，直到最近，使用电压敏感染料的成像主要限于心外膜表面。这项研究的目的是开发一种技术，使整个心肌壁的电激发的光学成像。具体来说，这项技术应该成像细丝，或组织中心的漩涡状电活动。这些被广泛认为是引起和维持心室颤动的原因，而细丝是它们行为的关键。 为了解决这一新技术的技术挑战，我们提出了一个协调项目，涉及A。纽约州立大学上州医科大学药理学系的Pertsov博士（PI），他是化学可兴奋系统和心脏中涡旋样兴奋的三维成像的先驱;波阿斯是哈佛医学院和马萨诸塞州综合医院核磁共振中心的光学断层扫描专家; Loew博士是康涅狄格大学健康中心生物医学成像技术中心（Co-PI）的负责人，该中心是电压敏感探针和光学成像的领导者; Weitz博士在哈佛大学物理系（Co-PI）工作，他们在光学成像和多重散射介质方面的专业知识闻名。 本课题的具体目标是：1）建立真实的计算机模型，用于从心肌组织跨膜电位的三维分布重建二维光学图像（正问题），2）将扩散光学层析成像应用于心脏中的实际电激活的3D重建（逆问题）; 3）设计、合成和在心肌组织中测试一系列近红外电压敏感染料，其被优化用于心脏中电激活的3D成像; 4）探索双光子荧光和二次谐波产生技术在亚细胞和亚毫米尺度上对心肌细胞和组织的电活动进行三维成像。该项目的成功完成将为一项新技术开辟道路，即心脏电激活的3D成像。