A novel near-infrared voltage-sensitive dye reveals the action potential wavefront orientation at increased depths of cardiac tissue

Recently, novel near-infrared (NIR) voltage-sensitive dyes were developed for imaging electrical activity in blood-perfused hearts and for tomographic applications. However, their usefulness for conventional surface mapping is unclear. The spectral shift to the NIR range significantly increases the penetration depth of light into the tissue, thus increasing the intramural volume contributing to the optical action potential (OAP). Here, we characterize both computationally and experimentally the effect of increased penetration depth on the OAP upstroke, the OAP component most sensitive to optical scattering and absorption, and the activation maps. Optical imaging of cardiac electrical activity was performed in isolated rat hearts (n = 3D5) paced from the LV mid free wall. We used the NIR dye JPW-6033 (excitation at 660 nm, acquisition at > 695 nm). The conventional dye DI-4-ANEPPS (excitation at 532 nm, acquisition at 700 DF50nm) was used for comparison. To simulate OAP we utilized a hybrid model that couples light transport equations with the model of electrical propagation. As expected, the switch from DI-4-ANEPPS to JPW-6033 significantly increased the upstroke duration: from 3.95 plusmn 0.69 ms to 5.39 plusmn 0.82 ms, respectively. However, activation maps were largely unaffected. The correlation between the shape of the optical upstroke, and the averaged subsurface wave front orientation was also preserved. The computer simulations are in excellent agreement with the experimental data. In conclusion, our analysis suggests that despite significant increase in upstroke duration, the novel NIR dyes can be a useful alternative to conventional dyes in surface mapping applications.