Key result
Photon scattering decreases the mutual information of optical voltage and calcium signals by 23% compared to unscattered signals during simulated ventricular fibrillation.
Photon scattering in optical mapping experiments artificially amplifies the measured dissociation between membrane voltage and intracellular calcium during ventricular fibrillation.
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Scattering correction is essential for optical mapping of VF; leaves open the true magnitude of voltage-calcium dissociation in intact hearts.
Recent optical mapping studies of cardiac tissue suggest that membrane voltage (V(m)) and intracellular calcium concentrations (Ca) become dissociated during ventricular fibrillation (VF), generating a proarrhythmic substrate. However, experimental methods used in these studies may accentuate measured dissociation due to differences in fluorescent emission wavelengths of optical voltage/calcium (V(opt)/Ca(opt)) signals. Here, we simulate dual voltage-calcium optical mapping experiments using a monodomain-Luo-Rudy ventricular-tissue model coupled to a photon-diffusion model. Dissociation of both electrical, V(m)/Ca, and optical, V(opt)/Ca(opt), signals is quantified by calculating mutual information (MI) for VF and rapid pacing protocols. We find that photon scattering decreases MI of V(opt)/Ca(opt) signals by 23% compared to unscattered V(m)/Ca signals during VF. Scattering effects are amplified by increasing wavelength separation between fluorescent voltage/calcium signals and respective measurement-location misalignment. In contrast, photon scattering does not affect MI during rapid pacing, but high calcium dye affinity can decrease MI by attenuating alternans in Ca(opt) but not in V(opt). We conclude that some dissociation exists between voltage and calcium at the cellular level during VF, but MI differences are amplified by current optical mapping methods.
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Bishop et al. (2011) studied Ventricular fibrillation. Photon scattering in dual voltage-calcium optical mapping vs. Unscattered signals was evaluated on Dissociation of electrical and optical signals quantified by mutual information (MI) (23% decrease in MI). Photon scattering decreases the mutual information of optical voltage and calcium signals by 23% compared to unscattered signals during simulated ventricular fibrillation.
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