Three-Dimensional Transcranial Ultrasound Imaging of Microbubble Clouds Using a Sparse Hemispherical Array

There is an increasing interest in bubble-mediated focused ultrasound (FUS) interventions in the brain. However, current technology lacks the ability to spatially monitor the interaction of the microbubbles with the applied acoustic field, something which is critical for safe clinical translation of these treatments. Passive acoustic mapping could offer a means for spatially monitoring microbubble emissions that relate to bubble activity and associated bioeffects. In this study, a hemispherical receiver array was integrated within an existing transcranial therapy array to create a device capable of both delivering therapy and monitoring the process via passive imaging of bubble clouds. A 128-element receiver array was constructed and characterized for varying bubble concentrations and source spacings. Initial in vivo feasibility testing was performed. The system was found to be capable of monitoring bubble emissions down to single bubble events through an ex vivo human skull. The lateral resolution of the system was found to be between 1.25 and 2 mm and the axial resolution between 2 and 3.5 mm, comparable to the resolution of MRI-based temperature monitoring during thermal FUS treatments in the brain. The results of initial in vivo experiments show that bubble activity can be mapped starting at pressure levels below the threshold for blood-brain barrier disruption. This study presents a feasible solution for imaging bubble activity during cavitation-mediated FUS treatments in the brain.