Synthesis of Voltage-Sensitive Fluorescence Signals from Three-Dimensional Myocardial Activation Patterns

Abstract

Voltage-sensitive fluorescent dyes are commonly used to measure cardiac electrical activity. Recent studies indicate, however, that optical action potentials (OAPs) recorded from the myocardial surface originate from a widely distributed volume beneath the surface and may contain useful information regarding intramural activation. The first step toward obtaining this information is to predict OAPs from known patterns of three-dimensional (3-D) electrical activity. To achieve this goal, we developed a two-stage model in which the output of a 3-D ionic model of electrical excitation serves as the input to an optical model of light scattering and absorption inside heart tissue. The two-stage model permits unique optical signatures to be obtained for given 3-D patterns of electrical activity for direct comparison with experimental data, thus yielding information about intramural electrical activity. To illustrate applications of the model, we simulated surface fluorescence signals produced by 3-D electrical activity during epicardial and endocardial pacing. We discovered that OAP upstroke morphology was highly sensitive to the transmural component of wave front velocity and could be used to predict wave front orientation with respect to the surface. These findings demonstrate the potential of the model for obtaining useful 3-D information about intramural propagation.

Photon scattering effects in optical mapping of propagation and arrhythmogenesis in the heart

“…This distortion in V opt upstroke depends sensitively upon the optical properties of the tissue (scattering and absorption coefficients), as well as on optical parameters associated with the particular experimental set-up (for example, the refractive index of the medium surrounding the heart). However, although V opt action potential upstrokes were prolonged with respect to those of V m , the specific dependence of V opt upstroke morphology upon intramural wavefront propagation direction, as found by Hyatt et al (10,11), was not documented in our study.…”

Depth-resolved optical imaging of transmural electrical propagation in perfused heart

“…Further, we assume that relative changes in quantum efficiency are greater than changes in the extinction coefficient (consistent with transmission measurements [5]), such that p x,m (r,t) ≈ ε x (r)c(r)η(r,t), and further that p x,m (r,t) ∝ V(r,t), or p x,m (r,t) = wV(r,t) where w is a scaling constant [30,31]. We also assume that the spectral shift in emission light (the underlying mechanism causing the change in η m ) is not sufficient to change the average tissue optical properties experienced by the detected emission light.…”

“…The poorer sensitivity to the deepest layers is also clear from the reconstruction of the electrical model data. Nevertheless, the direction of propagation, as well as a measure of the propagation speed can be determined from these images: By evaluating the gradient of the wavefront signal in these Z-T plots, we estimate that the velocities of transmural propagation for epi-and endo-cardial stimulation to be +45 and −51cm/s respectively which, while higher than in our electrical simulation, are within a physiologically reasonable range [31].…”

Construction and validation of anisotropic and orthotropic ventricular geometries for quantitative predictive cardiac electrophysiology

“…Figure 5c depicts a so-called V F Ã-map, where V F Ã is the fractional level at which the optical upstroke reaches a maximal derivative. As shown in previous studies [54,57,61], V F Ã can be used to infer the average subsurface wavefront orientation shown in figure 5d. The subsurface angle is positive for waves propagating away from the epircardial surface and negative for waves propagating towards the epicardium.…”