After cancer and heart disease, neurodegenerative diseases, such as Alzheimer's, Parkinson's, multiple sclerosis (MS), amythrophic lateral sclerosis (ALS), and neurological diseases take more lives each year than any other illness. Although great progress has been made in recent years toward understanding of central nervous system (CNS) diseases, few effective treatments and no cures are currently available. This is mainly because the blood-brain barrier (BBB) limits the delivery of the vast majority of systemically-administered drugs available to treat those diseases. The underlying hypothesis of this study is that delivery of therapeutic molecules is safe and effective through the blood-brain barrier (BBB) using Focused Ultrasound (FUS) in large animals in vivo. Our preliminary results have shown that the FUS technique can induce BBB opening entirely noninvasively, selectively and be monitored with MRI at sub-millimeter resolution in vivo. The specific aims are therefore to: 1) build a MRcompatible system for FUS targeting and monitoring in the MRI system; 2) test and demonstrate delivery of neurotrophic factors to the hippocampus and putamen of monkeys; 3) test and demonstrate delivery of inhibitors to the visual cortex of monkeys; and 4) assess the safety of the FUS method in monkeys.
In vivo imaging of sterile microglial activation in rat brain after disrupting the blood-brain barrier with pulsed focused ultrasound: [18F]DPA-714 PET study
