Advances in Focused Ultrasound for the Treatment of Brain Tumors

Abstract

Employing the full arsenal of therapeutics to treat brain tumors is limited by the relative impermeability of the blood-brain and blood-tumor barriers. In physiologic states, the blood-brain barrier serves a protective role by passively and actively excluding neurotoxic compounds; however, this functionality limits the penetrance of therapeutics into the tumor microenvironment. Focused ultrasound technology provides a method for overcoming the blood-brain and blood-tumor barriers through ultrasound frequency to transiently permeabilize or disrupt these barriers. Concomitant delivery of therapeutics has allowed for previously impermeable agents to reach the tumor microenvironment. This review details the advances in focused ultrasound in both preclinical models and clinical studies, with a focus on its safety profile. We then turn towards future directions in focused ultrasound-mediated therapies for brain tumors.

Keywords: blood–brain barrier; blood–tumor barrier; chemotherapy; glioma; immunotherapy; microbubble-enhanced focused ultrasound.

Figure 1

MB-FUS-mediated BBB disruption for therapy delivery. Normal vasculature consists of astrocytic endfeet surrounding endothelial cells linked by junctional complexes. MB-FUS disrupts these interactions to allow for passage of therapeutics into the tumor microenvironment. Arrows represent areas of disruption in the BBB. Created with BioRender.com.

Figure 2

Commercially available MB-FUS modalities. Exablate uses a fixed, hemispheric transducer which is separated from the patient by a layer of degassed water. The NaviFUS is a portable ultrasound transducer which allows for slightly more flexibility in treating various tumor localizations. Lastly, the Sonocloud-1 has an implantable transducer which connects to external equipment. This allows for a highly reproducible dose to be delivered to the TME over multiple treatments.