Hyperspectral Mapping of Cardiac Excitation and Contraction Dynamics

心脏兴奋和收缩动力学的高光谱图

• 批准号: 10038100
• 负责人: JUSTUS M ANUMONWO
• 金额: $ 24.5万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10038100
• 关键词: Ablation; Action Potentials; Adult; Advanced Development; Affect; Arrhythmia; Blood; Cardiac; Cardiomyopathies; Cell physiology; Cells; Clinic; Clinical; Clinical Research; Complex; Coupled; Coupling; Data; Dependence; Development; Disease; Dissociation; Dyes; Fluorescence; Fluorescent Dyes; Frequencies; Future; Generations; Goals; Gold; Health; Heart; Heart Atrium; Heart Diseases; Heart failure; Image; Image Analysis; Individual; Ion Channel; Isoproterenol; Label; Light; Lighting; Link; Maps; Measurement; Mechanics; Membrane; Membrane Potentials; Methods; Microscopic; Modeling; Monitor; Motion; Muscle Cells; Myopathy; Nature; Nifedipine; Optics; Pattern; Pharmacology; Phase; Physiological; Process; Property; Research; Role; Series; Sheep; Short Waves; Signal Transduction; Spectrum Analysis; Structure; Surface; Technology; Testing; Tetrodotoxin; Time; Tissues; Toxic effect; Visual; base; blebbistatin; cellular imaging; clinical application; clinically relevant; dosage; electrical property; heart function; heart imaging; imaging approach; imaging modality; imaging probe; in vivo; insight; mechanical properties; movie; novel; patch clamp; photonics; spatiotemporal; spectrograph; spectroscopic survey; transmission process; voltage; voltage/patch clamp

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.

项目概要/摘要 这是一项探索性研究的 R21 提案，旨在为实现新型体内 绘图技术改变了心脏机械和电激活波的临床研究。 动态机械心脏收缩与动态心脏收缩相关的复杂活动是双向耦合的。 收缩和兴奋动力作用以及解离的紊乱。 在它们的时空耦合中，它们是许多异常状况的基础，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方法来研究高度耦合和动态的 心脏体内的电和机械活动是同时进行的； 能够解析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。 收缩波和激励波的研究将能够确定它们在心脏中的个体和协作作用 因此，该提案的总体目标是证明新的无标记光子学的可行性。 对机械和电气相关活动的时空模式进行成像的方法，以提供 我们的发展将是对动态激发和收缩机制的多参数洞察。 基于短波红外（SWIR；~1-2.5 µm）光范围内的心脏电影格式成像， 相对较低的血液吸收和散射，最近被提出用于深层组织和 我们建议在这里使用绵羊心脏作为平台模型来检验以下一般假设： 无标记高光谱短波红外光成像将同时表征分离的动力学性质 该启动项目的具体目标是与心脏电活动和机械活动相关的因素。 目标 1：证明细胞固有高光谱 SWIR 光成像之间的分离 在这里，我们将识别 SWIR 范围内的波长。 吸光度水平特定于细胞内的动作电位或收缩。 SWIR 光成像对膜电流对细胞动作电位调节的不同敏感性 高光谱光吸光度的时间过程与作用之间的相关性。 目标 3：在血液中进行演示。 灌注离体羊心脏特定短波红外光带的表面反射率与 在这里，我们将优化新的映射方法。 例如，未来的体内临床应用，预计新的基于光子的方法将是安全且有效的。 为临床上终止心律失常的消融指导提供实时、准确的绘图。 这些目标的实现将带来一种全新的、无标记的体内成像模式 心脏的同步动态电和机械功能。