Histotripsy pulse-reflection for 3D image forming and bubble cloud localization in transcranial applications

Here, we present results from experiments using histotripsy pulses scattered off the surface of the skull, as well as bubble clouds generated within, to reconstruct 3D images of the exterior skull surface and localize bubbles within. These capabilities have the potential to provide image coregistration and real-time ultrasound monitoring for transcranial histotripsy treatment, without the need for MRI guidance. Histotripsy pulses were delivered to an ex vivo human skullcap mounted centrally within a 500 kHz, 256-element histotripsy transducer with transmit-receive capable elements. Straight-line ray tracing approximations based on the times-of-flight of the emitted pulses and the known geometry of the array were used to calculate points on the skull surface and to localize bubble clouds generated within. Using these methods, we were able to accurately locate and orient the skull within the array and generate a 3D map of its surface for coregistration with an a priori 3D scan. The points calculated based on the pulse-reflection from the skull were found to be within 1.25 mm of the surface measured in the a priori 3D scan. Using these signals, the calculated centroid of the generated bubble clouds was likewise found to be within 500 um of the measured focal point of the array through the skull.