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.

项目摘要/摘要 这是R21的提议，旨在建立迈向小说中的小说的初始步骤 映射技术转化了心脏中机械和电激活波的临床研究。 动态机械心脏收缩与动态相关的复杂活性双向耦合 电兴奋。收缩和兴奋动态动作中的疾病以及解离 在其时空耦合中，基于许多异常情况，包括致命的心力衰竭和心律不齐。 我们的长期目标是开发一种范式转移方法来研究高度耦合和动态的方法 体内心脏中的电和机械活动；该提议的主要前提是简单 能够解决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。有关单独动态模式的信息 收缩和兴奋的波将使他们的个体和合作在心脏中的作用 疾病。这是该提议的一般目标是证明新的无标签光子学的可行性 成像机械和电气相关活动的时空模式以提供的方法 多参数洞察动态兴奋和收缩力的机制。我们的发展将是 基于短波感染（SWIR; 〜1-2.5 µm）光范围的电影形式成像 相关的低血液吸收和散射，最近已提出了深层组织和 体内研究。我们建议在这里使用绵羊心作为平台模型，以检验一个普遍的假设 无标签的高光谱SWIR光成像将简单地表征分离的动态性质 与电和机械心脏活性相关的因素。这个启动项目的具体目标是 如下所示：目标1：证明细胞内在的高光谱SWIR光成像之间的分离 电和收缩相关的活动。在这里，我们将确定SWIR范围内的波长 吸光度水平特定于动作电位或细胞中的合同。目标2：确定 SWIR光成像对膜电流调制电位的差异灵敏度 监管机构。高光谱光吸收的时间顺序与动作之间的相关性 潜在和收缩将使成像的物理解释。目标3：在血液中表现出来 灌注孤立的绵羊心，特定的Swir光带的表面反射率与 电和机械相关波的传播。在这里，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，并且 提供实时和准确的映射，以指导消融以终止诊所的心律失常。全面的， 实现目标将导致一种全新的，无标签的成像方式，用于体内映射 心脏的同时动态电和机械功能。