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.

Differences Between Left and Right Ventricular Chamber Geometry Affect Cardiac Vulnerability to Electric Shocks

“…Note that the agreement between experiment and simulation regarding the shock-end transmembrane potential distribution is expected to be only qualitative because of depth averaging in the optical signal 26 -28 (ie, agreement only with regard to the pattern of shock-induced positive and negative polarization and not with respect to polarization magnitude). As demonstrated previously, depth averaging results in a significantly diminished optical signal magnitude 27,28 (for instance, optical signal maximum positive and negative polarization in the field of view is 27.8 and Ϫ66.9 mV for the RVϪ shock of 8V/cm, 50%APD and 13 and Ϫ51.26 mV for an LVϪ shock of 8V/cm, 50%APD, both shown in Figure 3A, versus 280 and Ϫ110 mV for the RVϪ shock of 6.4V/cm, 51%APD and 160 and Ϫ140 mV for the LVϪ shock of 6.4V/cm, 51%APD, both presented in Figure 3B). …”

Optical Imaging of the Heart

“…48,87,88 Furthermore, optical mapping presented evidence for 3D nature of ventricular reentry, which is sustained by scroll waves. 86,89 Despite the success of dynamic optical imaging of wavefronts and phase singularities during arrhythmias, there is still no agreement on the mechanisms that induce and sustain ventricular and atrial fibrillation. 90 Two competing dominant theories are being tested: the so-called "mother rotor" [91][92][93] and "break-up" 94 -98 hypotheses.…”

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

“…Complex filament orientation and filament bending is present in Figure 2A, right (filament shown in black with the ventricles rotated relative to the left-hand images). Thus, the interaction of 3D, rather than 1D, photon scattering, and the complex filament orientations associated with the anatomy of the organ itself, explains the large shift in phase singularity location between the V opt and V m maps, which is significantly larger than shifts of just 0.57 ± 0.16mm found by Bray & Wikswo, in their 1D scattering study (9). The shift in the positions of optically-recorded phase singularities, as found here, could have important implications for protocols which use the optical mapping technique to accurately localize phase singularities (14,15).…”

“…The studies described above had limited applicability because they ignored lateral scattering in planes parallel to the epicardium, where both excitation light intensity and fluorescent emission are strongest and thus likely to contribute to signal distortion. The landmark study by Hyatt et al was the first to analyze, for simplified model geometries, the optical signal distortion effects due to 3D photon scattering in cardiac tissue (9). The authors simulated the global movement and diffusion of fluorescent photons within a slab of ventricular tissue through an analytical solution to the 3D steady-state photon diffusion equation.…”