SUMMARY

Microbubble-enhanced focused ultrasound (MB-FUS) is an emerging technology especially for drug delivery in the brain as it enables non-invasive, reversible, and targeted physical opening of the blood-brain barrier (BBB). MB dynamics (i.e., radius changes) during FUS excitation is believed to play a key role in the efficacy and safety of this procedure. Thus, reproducible tuning of the MB dynamics to an effective strength while avoiding collapse of MB became essential. Number of past studies have proposed algorithms to control MB dynamics in the brain. However, a robust method that adapts to the highly non-linear bubble oscillation and dynamic environment in the brain is yet to be developed.
The overall objective of the project is to design and evaluate control methods to monitor and attain desired dynamics of both bubble clouds and single microbubble in the brain. Specific aims of the project are 1) to design a control algorithm to control MB cloud in the brain and assess the performance in healthy brain; 2) to assess efficacy of designed algorithm in therapy, specifically with anti-PD1 delivery and immunotherapy in glioblastoma (GBM); 3) to further refine control methods for controlling single microbubble’s radius using acoustic methods and theory; 4) to apply the algorithm in the brain and assess our abilities to induce different BBB phenotypes linked to promoted MB dynamics.
By bridging the MB dynamics with their biological responses, this work will not only refine our understanding on the role of MB dynamics during MB-FUS technology, but also support the development of novel therapeutic strategies against brain diseases (e.g., brain cancer immunotherapy). Furthermore, in combining MB-FUS treatments with existing therapeutic strategies, the ability to control the MB dynamics will ultimately support their safe application in humans along with the widespread application of this technology.