Extracorporeal Acute Cardiac Pacing by a Multi-Frequency High Intensity Focused Ultrasound: A Study of the Dominant Mechanisms in-Vivo and in-Silico

Extracorporeal acute cardiac pacing by high intensity focused ultrasound (HIFU) could be a disruptive technology in the field of cardiology, which may benefit congestive heart failure patients. Clinical application of this new cardiac pacing modality may allow to perform preoperative screening of patients prior to Cardiac Resynchronization Therapy; when today no noninvasive optimization method is available and 20-40% of implantation operations fail. In the study of the dominant mechanisms of HIFU pacing, we employed a multi frequency HIFU for pacing whole anesthetized rats. Our in-vivo observations allowed to define cavitation as the dominant ultrasound tissue interaction mechanism and membrane currents as the dominant cellular level mechanism. Herein, we present a mathematical model for testing the hypothesis that intermembrane cavitation may produce premature action potentials in model LV cardiomyocytes via membrane capacitance modulation. Our small animal in-silico modelling results accurately reconstructed our in-vivo results, our human model in-silico results predict that the threshold insonation patterns that were applied in rats would be suitable for cardiac pacing in humans without membrane disruption.