Synthesis of voltage-sensitive optical signals: application to panoramic optical mapping

Abstract

Fluorescent photon scattering is known to distort optical recordings of cardiac transmembrane potentials; however, this process is not well quantified, hampering interpretation of experimental data. This study presents a novel model, which accurately synthesizes fluorescent recordings over the irregular geometry of the rabbit ventricles. Using the model, the study aims to provide quantification of fluorescent signal distortion for different optical characteristics of the preparation and of the surrounding medium. A bi-domain representation of electrical activity is combined with finite element solutions to the photon diffusion equation simulating both the excitation and emission processes, along with physically realistic boundary conditions at the epicardium, which allow simulation of different experimental setups. We demonstrate that distortion in the optical signal as a result of fluorescent photon scattering is truly a three-dimensional phenomenon and depends critically upon the geometry of the preparation, the scattering properties of the tissue, the direction of wavefront propagation, and the specifics of the experimental setup. Importantly, we show that in an anatomically accurate model of ventricular geometry and fiber orientation, the morphology of the optical signal does not provide reliable information regarding the intramural direction of wavefront propagation. These findings underscore the potential of the new model in interpreting experimental data.

FIGURE 1

(A) Distribution of Φ_illum throughout the three-dimensional volume of the ventricles due to uniform epicardial illumination, showing the attenuation of the signal with depth into the myocardial wall. Locations of the slices through the ventricles are shown to be: apex-base (left) and anterior-posterior (right). The dashed-line in the apex-base slice refers to the position of the anterior-posterior slice; the dashed-line in the anterior-posterior slice refers to the position of the apex-base slice. (B) Plot of Φ_illum at each node point against the minimum geometric distance (r_min) of that point from the epicardium, along with a monoexponential decay function with δ = 0.57 mm.

FIGURE 2

V_m activation maps after apical (top) and endocardial (bottom) stimulation. Arrows in transmural views indicate the direction of wavefront propagation. Crosses mark the epicardial node from which the action potentials in Fig. 3 were recorded. Locations of the slices through the ventricles are apex-base (left) and anterior-posterior (right) as shown in Fig. 1.

FIGURE 3

Epicardial transmembrane electrical activity (V_m) and fluorescent optical signal (V_opt) after apical (top) and endocardial (bottom) stimulus. (A) V_m and V_opt action potentials taken from epicardial node marked in Fig. 2, with the upstroke region highlighted in B. (C) Surface distribution of V_m (left) and V_opt (right) 50 ms after apical stimulation (top) and 6 ms after endocardial stimulation (bottom), including transmural views. Locations of the slices through the ventricles for the V_m images are apex-base (right) and anterior-posterior (left) as shown in Fig. 1.

FIGURE 4

Variation of τ_opt with R_eff for apical (solid line, circles) and endocardial (dashed line, squares) stimulation protocols for the partial current boundary condition. Zero boundary condition solutions are also shown for the corresponding cases (solid line for apical, dashed line for endocardial stimulation).

FIGURE 5

Variation of τ_opt as the scattering properties of the tissue are varied. The penetration depth δ_eff (defined as ) during illumination and emission is varied individually for both apical and endocardial stimulation protocols. Panel A plots τ_opt vs. δ_eff during illumination and emission for apical stimulation; B shows the same for endocardial stimulation.