Transcranial spatial and temporal assessment of microbubble dynamics for brain therapies

Abstract

Harnessing ultrasound/microbubble interactions in the brain may make possible a number of therapeutic ultrasound applications, such as targeted drug delivery, sonothrombolysis, and cavitation-enhanced ablation. However, methods to guide these emerging therapies are presently lacking. Here, we integrated a linear US imaging transducer with a clinical transcranial MRI-guided focused ultrasound (MRgFUS) system and evaluated passive cavitation imaging to monitor microbubble-enhanced sonications. A nonhuman primate skull filled with brain-mimicking phantom was used for the experiments. First, we sonicated the phantom over a range of powers (20–60 W) to induce cavitation-enhanced heating. Using transcranial passive cavitation mapping and MR thermometry, we assessed the ability of the integrated system to simultaneously visualize temperature changes and microbubble activity. In another experiment, we traversed the phantom with a 2 mm channel through which microbubbles could flow and applied burst sonications (5 W) to generate stable and inertial cavitation. In the first experiment, cavitation activity and heating were colocalized. In the second, the location of the cavitation activity was coincident with the targeted location in the channel within the expected resolution of the passive imaging. We conclude that combined MR/ultrasound imaging can provide comprehensive guidance to simultaneously localize and quantify both acoustic cavitation activity and heating.