Voltage- sensitive fluorescence imaging on the heart surface

Optical methods provide a rather precise insight into cardiac electrical activity. Voltage- sensitive dyes like di 4-ANEPPS convert the electric signal into a fluorescent signal that can be measured by standard optical methods. A realistic picture of the dynamic patterns that govern electrical activity in the human heart can be obtained only with thick tissue preparations, from large animals. We measure the fluorescence signal of an approximately 2.5 times; 2.5 cm area on the surface of 8 mm thick porcine right ventricle preparations with a fast CCD camera at low magnification, and perform advanced simulations of the macroscopic dynamic features involved. To extract meaningful qualitative and quantitative data from these signals, details of the conversion from electrical to optical signal have to be known, and the problem of the 2D surface signal originating from a 3D distribution below has to be addressed. We compare experiment to simulation results applying a composite model based on both electrical and optical tissue properties. The model predicts optical action potential upstroke morphology, involving optical point spread functions and simplified Beeler- Reuter kinetics for the electrical wave propagation. Optical point spread functions have been calculated from scattering and absorption properties applying diffusion models and Monte- Carlo simulations. First of all, the forward problem has been solved for uniform light illumination and simulations have been compared to experiments. Furthermore, we also address the question of the inverse problem and provide an analysis of the limitations for this approach.