Abstract
Cardiac conduction maturation is an important and integral component of heart development. Optical mapping with voltage-sensitive dyes allows sensitive measurements of electrophysiological signals over the entire heart. However, accurate measurements of conduction velocity during early cardiac development is typically hindered by low signal-to-noise ratio (SNR) measurements of action potentials. Here, we present a novel image processing approach based on least squares optimizations, which enables high-resolution, low-noise conduction velocity mapping of smaller tubular hearts. First, the action potential trace measured at each pixel is fit to a curve consisting of two cumulative normal distribution functions. Then, the activation time at each pixel is determined based on the fit, and the spatial gradient of activation time is determined with a two-dimensional (2D) linear fit over a square-shaped window. The size of the window is adaptively enlarged until the gradients can be determined within a preset precision. Finally, the conduction velocity is calculated based on the activation time gradient, and further corrected for three-dimensional (3D) geometry that can be obtained by optical coherence tomography (OCT). We validated the approach using published activation potential traces based on computer simulations. We further validated the method by adding artificially generated noise to the signal to simulate various SNR conditions using a curved simulated image (digital phantom) that resembles a tubular heart. This method proved to be robust, even at very low SNR conditions (SNR = 2-5). We also established an empirical equation to estimate the maximum conduction velocity that can be accurately measured under different conditions (e.g. sampling rate, SNR, and pixel size). Finally, we demonstrated high-resolution conduction velocity maps of the quail embryonic heart at a looping stage of development.
Highlights
Cardiac electrophysiology has contributed directly to our understanding of heart diseases in the adult [1, 2]
Cardiac conduction system development starts at heart looping stages, when the tubular heart undergoes rapid structure changes including the formation of the primitive chambers and the emergence of cardiac cushions [14, 15]
4.1 Measuring activation time with a least squares fitting algorithm the function we used (Fig. 1) resembled a cardiac action potential, we could not properly validate goodness of fit with the actual action potential traces obtained from our optical mapping (OM) experiments, since we could not obtain noise-free signals
Summary
Cardiac electrophysiology has contributed directly to our understanding of heart diseases (e.g. arrhythmias) in the adult [1, 2]. Cardiac electrophysiology has become an integral part of understanding cardiac conduction system development and cardiac development in general [3,4,5,6,7,8,9,10,11,12]. The malformation of the conduction system during development often leads to congenital heart diseases [3, 13]. Cardiac conduction system development starts at heart looping stages, when the tubular heart undergoes rapid structure changes including the formation of the primitive chambers and the emergence of cardiac cushions (precursors for cardiac valves) [14, 15]. The conduction pattern undergoes drastic changes, including a rapid increase of conduction velocity in the primitive atrial and ventricular region [16, 17]. The conduction velocity in the atrioventricular junction (AVJ) remains relatively unchanged and significantly slower than either the atrial or
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