Real-Time Passive Acoustic Mapping With Enhanced Spatial Resolution in Neuronavigation-Guided Focused Ultrasound for Blood-Brain Barrier Opening.

Passive acoustic mapping (PAM) provides the spatial information of acoustic energy emitted from microbubbles during focused ultrasound (FUS), which can be used for safety and efficacy monitoring of blood-brain barrier (BBB) opening. In our previous work with a neuronavigation-guided FUS system, only part of the cavitation signal could be monitored in real time due to the computational burden although full-burst analysis is required to detect transient and stochastic cavitation activity. In addition, the spatial resolution of PAM can be limited for a small-aperture receiving array transducer. For full-burst real-time PAM with enhanced resolution, we developed a parallel processing scheme for coherence-factor-based PAM (CF-PAM) and implemented it onto the neuronavigation-guided FUS system using a co-axial phased-array imaging transducer. Simulation and in-vitro human skull studies were conducted for the performance evaluation of the proposed method in terms of spatial resolution and processing speed. We also carried out real-time cavitation mapping during BBB opening in non-human primates (NHPs). CF-PAM with the proposed processing scheme provided better resolution than that of traditional time-exposure-acoustics PAM with a higher processing speed than that of eigenspace-based robust Capon beamformer, which facilitated the full-burst PAM with the integration time of 10 ms at a rate of 2 Hz. In vivo feasibility of PAM with the co-axial imaging transducer was also demonstrated in two NHPs, showing the advantages of using real-time B-mode and full-burst PAM for accurate targeting and safe treatment monitoring. This full-burst PAM with enhanced resolution will facilitate the clinical translation of online cavitation monitoring for safe and efficient BBB opening.