Hyperspectral Mapping of Cardiac Excitation and Contraction Dynamics

项目摘要/摘要 这是一项探索性研究的R21提案，旨在建立通向体内新奇的初步步骤 标测技术改变了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的与动态相关的复杂活动 电刺激。收缩和兴奋动力学行为中的无序以及解离 在它们的时空耦合中，导致了许多异常情况，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研究高度耦合和动态的 心脏在活体内的电和机械活动；这一提议的中心前提是同时 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。关于分离的动力学模式的信息 收缩波和兴奋波将能够确定它们在心脏中的单独和协同作用 疾病。因此，本提案的总体目标是论证一种新的无标签光子学的可行性 用于成像机械和电气相关活动的时空模式以提供 动态兴奋和收缩机制的多参数洞察。我们的发展将是 基于短波红外(SWIR；~1-2.5微米)光范围内心脏的电影格式成像，它具有 相对较低的血液吸收和散射，这是最近提出的，对于深层组织和 活体研究。我们建议在这里使用羊心作为平台模型来检验一般假设 无标记高光谱SWIR光成像将同时表征分离的动力学性质 与心脏电活动和机械活动相关的因素。这个启动项目的具体目标是 具体内容如下：目标1：论证细胞固有高光谱SWIR光成像的可分性 与电和收缩相关的活动。在这里，我们将识别SWIR范围内的波长 吸光度水平与细胞的动作电位或收缩有关。目标2：确定 SWIR光成像对膜电流调制细胞动作电位的微分敏感性 监管者。高光谱光吸光度的时程与作用的相关性 电势和收缩将使对成像的生理解释成为可能。目标3：用鲜血证明 灌流离体羊心脏特定SWIR光带表面反射率与心脏的关系 电波和机械波的传播。在这里，我们将优化新的映射方法以 未来在体内的临床应用。例如，预见到的基于光子的新方法将是安全的和 为临床指导消融终止心律失常提供实时、准确的标测。总的来说， 这些目标的实现将带来一种全新的、无标记的成像方式，用于活体标测 心脏同时具有动态的电和机械功能。

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.