Empirical Model of Focused Ultrasound-Mediated Treatment for Chemotherapy Delivery to Brain Tumors

Abstract

Focused ultrasound (FUS) has emerged as a transformative technique for enhancing drug delivery to brain tumors by temporarily and locally disrupting the blood-brain barrier (BBB). Despite significant progress in both pre-clinical and clinical research, a major challenge remains: the absence of a model that connects the properties of drug particles and FUS sonication parameters to therapeutic effectiveness. In this study, we introduce a novel empirical model that integrates key factors, including drug pharmacodynamics, microbubble kinetics for BBB disruption, intrabrain ultrasound signal propagation, and skull-thickness variations. The model defines a new sonication parameter that encapsulates ultrasound signal characteristics and predicts the concentration of therapeutic agents internalized or bound to DNA with an accuracy exceeding 82%. By employing data from previous pre-clinical studies, this model facilitates the development of precise sonication protocols tailored for clinical applications. These advancements represent a significant step toward personalized FUS-mediated treatments, bridging the gap between experimental research and patient-centered therapies.