CAREER: Ultrasound-induced drug delivery through the blood-brain barrier

Columbia University, New York NY

Investigators

Abstract

CBET-0644713 Konofagou The project will determine the range of intensities, frequencies and other parameters of focused ultrasound (FUS) that can be used to temporarily (i.e. reversibly) open the blood brain barrier (BBB) without concomitant thermal or mechanical damage to neurons and endothelial and other tissues. The preliminary work of the PI has demonstrated that via focused ultrasound (FUS) one can open the BBB in a controlled manner. The project will explore the possibilities under which the BBB can open reversibly, noninvasively, and with regional selectivity using FUS. The specific aims are: 1) understand transcranial ultrasound propagation and induced biological effects through an in-depth theoretical analysis; 2) Investigate the mechanisms under which FUS induces reversible BBB opening in hippocampal cells in vitro; and 3) Characterize the FUS method for optimized drug delivery in wildtype and Alzheimer's-disease affected mice. The project addresses very challenging topic-reversibly opening BBB and combines mathematical models to predict the localization of FUS and in vitro and in vivo experiments. The project utilizes ultrasound energy to temporarily open the blood brain barrier without damaging any tissue. Such modality would have a broad impact for treatments of central nervous system (CNS) diseases. The educational aims include introduction of a new course based on therapeutic use of ultrasound and ultrasound/tissue interaction and use of industrial internship at a graduate level.