The use of TRA focusing of ultrasound to improve the effectiveness of convection-enhanced delivery of drugs to the brain.

The goal of this project was to develop an acoustic system for accurate focusing ultrasound to selected sites in the brain to improve convection enhanced delivery (CED) of drugs. CED is a promising method of drug delivery to the brain for the treatment of several disorders, including glioblastoma multiforme, a high-grade glioma that presents an especially poor prognosis for patients. CED bypasses the blood-brain barrier by infusing compounds through a needle directly into brain parenchyma or brain tumor. CED has been tested extensively in animals and humans to deliver a variety of agents including small molecules, proteins, chemotherapeutics, and viral vectors. The current challenge in CED therapy is to enhance the penetration of infused drugs into the brain while maintaining control over the spatial distribution of the infusate. Our studies confirmed that the use of TRA focusing of ultrasound technology may meet this challenge. In collaboration with Cornell University we developed a technology to enhance the delivery of therapeutics to targeted regions in the brain based on TRA principles (see Figure 2). This project also addresses the most vexing issue facing practitioners of CED therapy – how to control the distribution of infused drugs to optimize therapeutic benefits and improve patient outcomes.

TRA reverberator coupled to rodent skull and needle-hydrophone inserted into rodent caudate. The upper insert shows the acoustic pressure along the needle path. The bottom insert shows the enhancement of drug delivery due to TRA focused ultrasound sonication.