The road ahead to successful BBB opening and drug-delivery with focused ultrasound.

ABSTRACT

This review delves into the innovative technology of Blood-Brain Barrier (BBB) opening with low-intensity focused ultrasound in combination with microbubbles (LIFU-MB), a promising therapeutic modality aimed at enhancing drug delivery to the central nervous system (CNS). The BBB's selective permeability, while crucial for neuroprotection, significantly hampers the efficacy of pharmacological treatments for CNS disorders. LIFU-MB emerges as a non-invasive and localized method to transiently increase BBB permeability, facilitating the delivery of therapeutic molecules. Here, we review the procedural stages of LIFU-MB interventions, including planning and preparation, sonication, evaluation, and delivery, highlighting the technological diversity and methodological challenges encountered in current clinical applications. With an emphasis on safety and efficacy, we discuss the crucial aspects of ultrasound delivery, microbubble administration, acoustic feedback monitoring and assessment of BBB permeability. Finally, we explore the critical choices for effective BBB opening with LIFU-MB, focusing on selecting therapeutic agents, optimizing delivery methods, and timing for delivery. Overcoming existing barriers to integrate this technology into clinical practice could potentially revolutionize CNS drug delivery and treatment paradigms in the near future.