Examination of optical depth effects on fluorescence imaging of cardiac propagation

Abstract

Optical mapping with voltage-sensitive dyes provides a high-resolution technique to observe cardiac electrodynamic behavior. Although most studies assume that the fluorescent signal is emitted from the surface layer of cells, the effects of signal attenuation with depth on signal interpretation are still unclear. This simulation study examines the effects of a depth-weighted signal on epicardial activation patterns and filament localization. We simulated filament behavior using a detailed cardiac model, and compared the signal obtained from the top (epicardial) layer of the spatial domain with the calculated weighted signal. General observations included a prolongation of the action upstroke duration, early upstroke initiation, and reduction in signal amplitude in the weighted signal. A shallow filament was found to produce a dual-humped action potential morphology consistent with previously reported observations. Simulated scroll wave breakup exhibited effects such as the false appearance of graded potentials, apparent supramaximal conduction velocities, and a spatially blurred signal with the local amplitude dependent upon the immediate subepicardial activity; the combination of these effects produced a corresponding change in the accuracy of filament localization. Our results indicate that the depth-dependent optical signal has significant consequences on the interpretation of epicardial activation dynamics.

FIGURE 1

(a, Left) A three-dimensional intramural scroll wave and associated filament (black line) at t = 400 ms; double arrow shows longitudinal fiber direction, spatial units are in cm. (Right) Cross-section AA′ showing the position of the scroll wave and associated singularity (unfilled circle, with the subsequent singularity trajectory from t = 400–580 ms shown as a white line), and the two recording locations on the epicardium (1 and 2). Time traces at point (1) are shown in b; time traces at point (2) are shown in c. u₀ drawn as dashed line, drawn as solid line. Panels on the right are insets of an interval from t = 400–580 ms indicated with a box in the left panels.

FIGURE 2

Time-space plots of u from the epicardial surface. (a) Top layer of nodes. Solid white lines show average slope of activation. (b) Weighted average. (c) Difference between a and b. Epicardial breakthroughs labeled as EB, additional secondary depolarizations labeled as AD. Initial transient of 50 ms not shown.

FIGURE 3

Snapshots of the temporal development of the depth-weighted and top layer signals. (Top panels) (green) and u₀ (blue) signals as a function of x. (Bottom panels) Corresponding scroll wave cross-section, with the filament trajectory overlaid as white line. Figure shows wave traversing a above and b below the core, as traced out by the white line.

FIGURE 4

Snapshots of the temporal development of the depth-weighted and epicardial signals for an L-shaped filament. (a) Three-dimensional tissue slab with filament in black. Arrow shows the orientation of the filament as seen from the z = 0 plane. u shown on bounding surfaces. (b) Snapshot of u₀ and and epicardial signals: u₀ (left), (middle), and − u₀ (right). Trajectory of the filament on the bounding surfaces in a and b shown as a white line. (c) Epicardial activation 4-ms isochrone map of for the area outlined in a, showing the linear core of the scroll wave. Arrow is the same as that shown in a. (d) Traces of (green) and u₀ (blue) as a function of time at the locations numbered in c. Red circles indicate the presence of additional peaks in .

FIGURE 5

Comparison of and u₀ signals during spiral wave breakup. Regions of interest are colored to highlight details. (a) Diminished magnitude; (b) apparent supramaximal conduction velocity in u₀, arrow shows direction of propagation; (c) epicardial breakthrough; and (d) subepicardial graded potentials in arrow shows direction of subepicardial propagation.

FIGURE 6

Illustration of phase singularity localization as a function of (x,y,t) during a 20-ms segment of fibrillatory activity in the MBR model. Trajectories from u₀ and shown in blue and green, respectively. The singularities are labeled with numbers.