Histotripsy cardiac therapy system integrated with real-time motion correction.

Histotripsy has shown promise in non-invasive cardiac therapy for neonatal and fetal applications. However, for cardiac applications in general, and especially in the adult heart, cardiac and respiratory motion may affect treatment accuracy and efficacy. In this article, we describe a histotripsy-mediated cardiac therapy system integrated with a fast motion tracking algorithm and treatment monitoring using ultrasound imaging. Motion tracking is performed by diamond search block matching in real-time ultrasound images using a reference image of the moving target, refined by Kalman filtering. As proof of feasibility, this algorithm was configured to track 2-D target motion and then electronically adjust the focus of a 1-MHz annular therapy array to correct for axial motion. This integrated motion tracking system is capable of sub-millimeter accuracy for displacements of 0-15 mm and velocities of 0-80 mm/s, with a maximum error less than 3 mm. Tissue phantom tests indicated that treatment efficiency and lesion size using motion tracking over displacements of 0-15 mm and velocities of 0-42 mm/s are comparable to those achieved when treating stationary targets. In vivo validation was conducted in an open-chest canine model, where the system provided 24 min of motion-corrected histotripsy therapy in the live beating heart, generating a targeted lesion on the atrial septum. Based on this proof of feasibility and the natural extension of these techniques to three dimensions, we anticipate a full motion correction system would be feasible and beneficial for non-invasive cardiac therapy.