Hyperspectral Mapping of Cardiac Excitation and Contraction Dynamics

项目概要/摘要 这是一项探索性研究的R21提案，旨在建立一种新的体内 标测技术将改变心脏机械和电激活波的临床研究。 动态机械心脏收缩是双向耦合到与动态心脏收缩相关的复杂活动。 电激励收缩和兴奋动力学行为的紊乱，以及解离 在它们的时空耦合中，是许多异常情况的基础，包括致命的心力衰竭和心律失常。 我们的长期目标是开发一种范式转换的方法来研究高度耦合和动态的 电和机械活动的心脏在体内;这个建议的中心前提是， 能够分辨机械和电活动的时空映射对于 了解心脏健康和疾病的机制。关于分离动力学模式的信息 收缩波和兴奋波的相互作用将能够确定它们在心脏中的单独作用和协同作用。 疾病因此，本提案的总体目标是证明新的无标记光子学的可行性 一种用于对机械和电相关活动的时空模式进行成像的方法， 多参数洞察机制的动态兴奋和收缩性。我们的发展将是 基于短波红外（SWIR; ~1-2.5 µm）光范围内的心脏电影格式成像， 相对低的血液吸收和散射，并且最近已经提出用于深层组织和 体内研究。我们建议在这里使用绵羊心脏作为平台模型来测试一般假设， 无标记的高光谱短波红外光成像将同时表征分离的动力学性质， 与电和机械心脏活动相关的因素。该启动项目的具体目标是 目的1：证明细胞的固有高光谱SWIR光成像之间的分离性， 电和收缩相关活动。在这里，我们将确定SWIR范围内的波长， 吸光度水平对细胞中的动作电位或收缩是特异性的。目标2：确定 SWIR光成像对膜电流对细胞动作电位调制的不同敏感性 监管部门高光谱吸光度的时间过程与作用之间的相关性 电势和收缩将使得能够对成像进行生理学解释。目的3：在血液中演示 灌流的离体绵羊心脏的表面反射率之间的关系， 电波和机械波的传播。这里我们将优化新的映射方法， 未来的体内临床应用。例如，可预见的新的基于光子的方法将是安全的， 提供实时和准确的标测，用于指导消融以终止临床心律失常。总的来说， 这些目标的实现将导致一种全新的、无标记的成像模式，用于体内映射， 心脏的同时动态电功能和机械功能。

PROJECT SUMMARY/ABSTRACT This is an R21 proposal for an exploratory research aiming to establish the initial steps toward a novel in vivo mapping technology to transform the clinical study of mechanical and electrical activation waves in the heart. The dynamic mechanical cardiac contraction is two-way coupled to the complex activity associated with dynamic electrical excitations. Disorders in the contraction and excitation dynamical actions, as well as the dissociation in their spatiotemporal coupling, underlie many abnormal conditions, including fatal heart failure and arrhythmias. Our long term goal is to develop a paradigm-shifting approach for studying the highly coupled and dynamic electrical and mechanical activities in the heart in vivo; the central premise of this proposal is that a simultaneous spatiotemporal mapping capable of resolving the mechanical and the electrical activities is critical for understanding mechanisms of health and disease in the heart. Information on the separated dynamical patterns of contraction and excitation waves will enable determining their individual and cooperative role in cardiac disease. Thus, the general objective of this proposal is to demonstrate the feasibility of a new label-free photonics approach for imaging the spatiotemporal patterns of mechanical and electrical associated activities to provide multi-parametric insight into mechanisms of dynamical excitation and contractility. Our developments will be based on movie-format imaging of the heart at short-wave infrared (SWIR; ~1-2.5 µm) light range, which has relatively low blood absorbance and scattering, and which has been proposed recently for both deep tissue and in vivo studies. We propose to use here the sheep heart as a platform model to test the general hypothesis that label-free hyperspectral SWIR light imaging will simultaneously characterize the separated dynamical nature of factors associated with electrical and mechanical cardiac activity. The specific aims in this launching project are as follows: Aim 1: To demonstrate the separability between intrinsic hyperspectral SWIR light imaging of cellular electrical and contraction associated activities. Here we will identify wavelengths in the SWIR range whose absorbance level is specific to the action potential or the contraction in the cell. Aim 2: To determine the differential sensitivity of SWIR light imaging to modulations of the cellular action potential by membrane currents regulators. The correlation between the time-course of the hyperspectral light absorbance and the action potential and contraction will enable a physiological interpretation of the imaging. Aim 3: To demonstrate in blood perfused isolated sheep hearts the relationship between surface reflectance of specific SWIR light bands and propagation of electrical and mechanical associated waves. Here we will optimize the new mapping method for future in vivo clinical application. For example, the foreseen new photonic-based approach will be safe and provide real-time and accurate mapping for guidance of ablation to terminate arrhythmias in the clinic. Overall, accomplishment of the aims will lead to an entirely new, label-free imaging modality for in vivo mapping of simultaneous dynamic electrical and mechanical function of the heart.