Because glioblastoma deeply infiltrates brain tissue, surgery is of limited efficacy. The tumor inevitably recurs, with the result that patients with glioblastoma have a life expectancy of only 14 months. There are therapies that might prove effective, but the blood-brain barrier, designed to protect the brain from harmful substances, also keeps them out. A world-renowned expert in focused ultrasound, Richard Price has received two National Institutes of Health RO1 awards to make the blood-brain barrier selectively permeable. Price is the Lawrence R. Quarles Professor in the Department of Biomedical Engineering at the University of VIrginia. R01EB030744The first award would deliver gene-therapy agents that alter the genome of specific blood-brain barrier cells, thus affecting its porosity. The award's Public Health Relevance Statement reads, "The blood-brain barrier is a specialized feature of brain capillaries that protects brain tissue from harmful substances that may be present in blood. Dysfunction of this barrier contributes to many brain pathologies; therefore, the development of minimally-invasive approaches capable of modulating genes in the blood-brain barrier would represent a powerful technology. To this end, in this proposal, we will develop a therapeutic approach that uses MR image-guidance and focused ultrasound energy to deliver gene-therapy agents that modulate the genome of the blood-brain barrier with high spatial precision." R01EB030409The second award would use focused ultrasound to temporarily open the blood-brain barrier to a controlled-release nanoparticle formulation that has the potential to control tumor growth, block infiltration and improve survival. The award's Public Health Relevance Statement reads, "Chemotherapy is often ineffective when treating primary brain tumors because the interface between the bloodstream and the brain, which is called the blood-brain barrier, is not permeable to drugs in the bloodstream. Further, even those drugs that are delivered across the blood-brain barrier do not penetrate tissue effectively. In this proposal, we are testing whether the combination of an MR image-guided drug delivery approach that uses focused ultrasound to temporarily open the blood-brain barrier and a controlled- release nanoparticle formulation that penetrates brain tumor tissue can be used to effectively primary brain tumors."