Glioblastoma multiforme (GBM) has a 5-year survival rate of only 12%, due primarily to the inability of chemotherapeutic drugs to cross the blood brain barrier (BBB). The goal of this proposal is to improve GBM therapy by coupling MR-guided BBB opening via focused ultrasound (FUS) and microbubbles (MBs) with drug-loaded nanoparticles that efficiently penetrate brain tissue. Here, we will first define FUS pressure thresholds for safe and reversible BBB opening to an MR contrast agent (gadolinium) in invasive intracranial brain tumors. Next, we will determine optimal conditions for delivering brain penetrating nanoparticle (BPN) formulations. Once completed, these studies will have provided the foundation for future studies in which therapeutic BPNs are delivered across the BBB to inhibit tumor growth and improve animal survival.