Background: The heart's contractions are triggered by action potential and calcium waves wich propagate through the cardiac muscle at high speeds. Imaging the contracting tissue as well as the electrophysiological wave phenomena simultaneously has remained a challenge, in parts because it lacked the numerical methods to process the corresponding imaging data. For instance, in the past, almost all optical mapping studies were performed with contraction-inhibited hearts uncoupled with pharmacological excitation-contraction uncoupling substances. As a consequence, there are very few studies in which optical imaging and structural imaging, such as ultrasound, is combined to measure the heart's electrophysiology and mechanics simultaneously.
Aims: Here, we introduce a high-resolution ex vivo imaging system which comprises panoramic optical mapping and high-speed 4D ultrasound imaging. We use the system to study the electromechanics of isolated hearts at high spatial and temporal resolutions.
Methods: The optical system comprises up to 24 high-speed cameras with which we image action potential and/or calcium waves on the entire contracting heart surface. We use three-dimensional multi-view motion tracking and ratiometric imaging to compensate motion artifacts and measure action potential waves as well as strain across the surface of isolated hearts placed inside a custom-designed soccer ball-shaped imaging chamber. The chamber facilitates even illumination with pulsed excitation light and imaging in a panoramic fashion. While generating three-dimensional reconstructions of the entire deforming ventricular surface with corresponding high-resolution voltage-sensitive optical measurements, we cross-register the superficial optical data with three-dimensional ultrasound data using cross-registration calibration targets.
Results: With our setup, we can image action potential and calcium waves as well as ventricular deformation mechanics at unprecedented resolutions during sinus rhythm, paced rhythms as well as during tachyarrhythmias.
Conclusion: Our imaging setup defines a new state-of-the-art in the field, and can be used to study the heart's electromechanical dynamics during health and disease.