Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review

Abstract

Optical techniques for recording and manipulating cellular electrophysiology have advanced rapidly in just a few decades. These developments allow for the analysis of cardiac cellular dynamics at multiple scales while largely overcoming the drawbacks associated with the use of electrodes. The recent advent of optogenetics opens up new possibilities for regional and tissue-level electrophysiological control and hold promise for future novel clinical applications. This article, which emerged from the international NOTICE workshop in 20181, reviews the state-of-the-art optical techniques used for cardiac electrophysiological research and the underlying biophysics. The design and performance of optical reporters and optogenetic actuators are reviewed along with limitations of current probes. The physics of light interaction with cardiac tissue is detailed and associated challenges with the use of optical sensors and actuators are presented. Case studies include the use of fluorescence recovery after photobleaching and super-resolution microscopy to explore the micro-structure of cardiac cells and a review of two photon and light sheet technologies applied to cardiac tissue. The emergence of cardiac optogenetics is reviewed and the current work exploring the potential clinical use of optogenetics is also described. Approaches which combine optogenetic manipulation and optical voltage measurement are discussed, in terms of platforms that allow real-time manipulation of whole heart electrophysiology in open and closed-loop systems to study optimal ways to terminate spiral arrhythmias. The design and operation of optics-based approaches that allow high-throughput cardiac electrophysiological assays is presented. Finally, emerging techniques of photo-acoustic imaging and stress sensors are described along with strategies for future development and establishment of these techniques in mainstream electrophysiological research.

Portable low-cost macroscopic mapping system for all-optical cardiac electrophysiology

“… 44 Detailed experimental descriptions and adherence to standard experimental approaches are viewed as a way toward easier comparison of findings obtained by different laboratories. Yet, the complexity of experiments in cardiac electrophysiology, as an evolving field, using a variety of experimental models, variety of configurations and reagents, and with the adoption of new technologies, e.g., innovative optical tools, 3 often prevents comprehensive analysis and consideration of all aspects that may impact the results.…”

“…The system can be used in culture medium at elevated temperature (Figs. [3][4][5] for potential long-term recordings of activity in human iPSC-CMs. As suggested in Fig.…”

Portable low-cost macroscopic mapping system for all-optical cardiac electrophysiology

“…Detailed experimental descriptions and adherence to standard experimental approaches are viewed as a way towards easier comparison of findings obtained by different laboratories. Yet, the complexity of experiments in cardiac electrophysiology, as an evolving field, using a variety of experimental models, variety of configurations and reagents, and with the adoption of new technologies, e.g., novel optical tools 3 , often prevents comprehensive analysis and consideration of all aspects that may impact the results.…”

“…Functional optical mapping of cardiac electrophysiology has become indispensable in the quantification of arrhythmia emergence and mechanisms, including in recently more widely used human induced stem-cell derived cardiomyocytes, iPSC-CMs [1][2][3] . Microscope-based optical mapping in cultured cells using fluorescent dyes for voltage and calcium yields acceptable signalto-noise ratio (SNR) due to the optimized high-NA optics 4 .…”

Phenomenological analysis of simple ion channel block in large populations of uncoupled cardiomyocytes

“…The action potential duration (APD) and its change under drug action (∆ APD) are, therefore, primary biomarkers used to guide the design of anti-arrythmic drugs and quantify their pharmacodynamics (Corrias et al, 2010). Novel optics-based techniques in cardiac electrophysiology have now made it possible to design high-throughput systems capable of measuring APD and other secondary AP waveform biomarkers at rates of up to 200 cells/hr (Warren et al, 2010;Lachaud et al, 2018;Müllenbroich et al, 2021). In our recent study (Lachaud et al, 2022), AP characteristics of nearly 500 uncoupled cardiomyocytes were measured using voltage-sensitive fluorescent dyes.…”