Sonication Tuning in Focused Ultrasound Multi-Target Brain Tumor Therapy

Focused ultrasound (FUS) combined with microbubbles has emerged as an effective technique for enhancing drug delivery across the stringent blood-brain barrier (BBB). However, tuning up FUS-sonicating parameters that lead to the desired uniform drug distribution at the target spots remains a challenge due to underlying biophysiological complexity, particularly in multi-target scenarios. Here, we propose a novel system model that characterizes the relationship between external actuating signals and therapeutic responses within a Multiple-Input Multiple-Output (MIMO) framework. We observe the drug delivery pathway as a communication channel, where transvascular and intratumoral pharmacokinetics introduce effects equivalent to channel distortion and interference, further leading to non-uniform drug distribution and unintended accumulation in healthy tissues. To mitigate these effects, we develop an equivalent channel matrix and exploit a known concept of precoding scheme with the aim to optimize sonication parameters in a way to ensure uniform and effective drug delivery across all targeted regions. We numerically demonstrate our approach using available preclinical data on low-intensity FUS-mediated chemotherapy for brain tumors.