Depth-resolved imaging of myocardial excitation

描述(申请人提供)：了解心脏电传导异常的机制是开发有效的抗心律失常疗法的关键。在过去的十年里，使用电压敏感的荧光染料对心脏中的电激发波进行成像的研究取得了重大进展。然而，直到最近，使用电压敏感染料的成像主要局限于心外膜表面。因此，心肌壁内电活动可视化工具的设计可能会对该领域产生重大影响。这项研究的最终目标是开发一种新的光学成像技术，用于检测隐藏在心肌壁内的心律失常来源。这项新技术将把扩散光学断层扫描的方法与心脏电过程及其特征的特定知识结合起来。迈向我们主要目标的第一大步将是创建一系列现实的特定于组织和特定于染料的计算机模型，用于从心肌组织中跨膜电位的3D分布重建光学图像(正问题)。使用这种方法，称为虚拟光学成像(VOI)，我们将创建一个网络可访问的库，其中包含主要类型的激活模式的光学签名。正问题的求解将为反问题的求解提供关键要素--从光信号中重建跨膜电位的三维分布。该项目的具体目标是：1)基于对光吸收和散射的直接测量，开发一个真实的光在心肌组织中传输的模型。2)将光传输模型与电波传播模型进行耦合。这一组合将预测正常传播和三维折返活动期间依赖于电压的光学信号。3)开发和验证用于成像壁内兴奋源的实验技术和去卷积算法，包括产生径向传播的激发的异位焦点和心肌组织中3D折返活动的组织中心--卷曲波丝。该项目的成功完成将大大提高人们解释光学记录的能力，并最终使深度分辨探测器能够对最致命的心律失常背后的壁内源进行成像。

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 that uses voltage-sensitive dyes was limited primarily to the epicardial surface. Therefore the design of tools for visualization of electrical activity inside the myocardial wall is likely to have a major impact on the field. The ultimate goal of the proposed studies is to develop a new optical imaging technology for detecting sources of arrhythmia hidden inside the myocardial wall. The new technology will combine methods of diffusive optical tomography with specific knowledge of electrical processes in the heart and their characteristics. The first major step towards our main objective will be to create a family of realistic tissue-specific and dye-specific computer models for reconstructing optical images from 3D distributions of the transmembrane potential in myocardial tissue (forward problem). Using this methodology, termed below virtual optical imaging (VOI), we will create a web-accessible library containing the optical signatures of major types of activation patterns. The solution of the forward problem will provide key elements for solving the inverse problem - reconstructing 3D distributions of the transmembrane potential from optical signals. The specific aims of the project are: 1) To develop a realistic model of light transport in myocardial tissue based on direct measurements of light absorption and scattering. 2) To couple the light transport model to a model of electrical wave propagation. The combination will predict voltage-dependent optical signals during normal propagation and 3-dimensional reentrant activity. 3) To develop and validate experimental techniques and deconvolution algorithms for imaging intramural sources of excitation including ectopic foci producing radial spread of excitation, and scroll wave filaments - the organizing centers of 3D reentrant activity in myocardial tissue. Successful completion of the project should significantly improve ones ability to interpret optical recordings and will ultimately enable depth-resolving detectors for imaging the intramural sources underlying the most lethal arrhythmias.