Monitoring and Delivery of Transcranial Therapy Using Dual-mode Ultrasound

Abstract: Transcranial focused ultrasound (tFUS) is gaining increased attention as a noninvasive tool for a number of therapies, e.g. essential tremor, neuromodulation, tumor ablation, etc. In addition, recent results demonstrating the feasibility tFUS-mediated blood brain barrier opening promise to extend the therapeutic applications of tFUS to a myriad of conditions and diseases of the brain. The majority of the published work employ MRI for monitoring and, in some applications, control of tFUS exposure or its bioeffects. While this imaging modality has proved to be essential to advancing tFUS applications so far, the precise delivery of localized tFUS still faces major challenges due to the uncertainties of wave propagation through the skull. This could present a major barrier towards the widespread safe and ef?cacious use of FUS in transcranial therapies. The long-term objective is to develop a real-time system for monitoring and delivering transcranial FUS therapies in patients using dual-mode ultrasound (DMUA) systems. DMUAs are capable of operating in both therapy and imaging modes in real-time allowing for immediate feedback on tFUS-tissue interactions at the target as well as the intervening and surrounding tissues, including the scalp and skull. We propose to develop real-time refocusing algorithms to improve the safety and ef?cacy of tFUS therapy of targeted structures within the brain. We present preliminary data demonstrating the feasibility of refocusing and propose to extend our results to wideband tFUS application. This approach maximizes the bandwidth of the imaging/therapy pulses to improve the localization and heating ef?ciency at the target while minimizing exposure to the skull. The DMUA approach is uniquely capable of providing this kind of feedback due to the inherent registration between the imaging and therapeutic coordinate systems. In addition to the multiband adaptive refocusing method, we propose to develop imaging methods to characterize the quality of tFUS in vivo and ex vivo at the target and critical points on the skull. This includes the development of a quantitative method to estimate the heating rate. This quantitative measurement will provide speci?c feedback for assessing the improvement due to adaptive refocusing. Finally, we propose to test and validate the refocusing and heating rate estimation method in vivo rat model of chronic temporal lobe epilepsy.