Inverse estimation of cardiac activation times via gradient-based optimization

Computational modeling may provide a quantitative framework for integrating multiscale data to gain insight into mechanisms of heart disease, identify and test pharmacological and electrical therapy and interventions, and support clinical decisions. Patient-specific computational cardiac models can help guide such procedures, and cardiac inverse modeling is a promising alternative to adequately personalize these models. Indeed, full cardiac inverse modeling is currently becoming computationally feasible; however, fundamental work to assess the feasibility of emerging techniques is still needed. In this study, we use a partial differential equation-constrained optimal control approach to numerically investigate the identifiability of an initial activation sequence from synthetic (partial) observations of the extracellular potential using the bidomain approximation and 2D representations of cardiac tissue. Our results demonstrate that activation times and duration of several stimuli can be recovered even with high levels of noise, that it is sufficient to sample the observations at the electrocardiogram-relevant sampling frequency of 1 kHz, and that spatial resolutions that are coarser than the standard in electrophysiological simulations can be used. The optimization of activation times is still effective when synthetic data are generated with a different cell membrane kinetics model than optimized for. The findings thus indicate that the presented approach has potential for finding activation sequences from clinical data modalities, as an extension to existing cardiac imaging approaches.