Real-time, transcranial monitoring of safe blood-brain barrier opening in non-human primates

The delivery of drugs to specific neural targets faces two fundamental problems: most drugs do not cross the blood-brain barrier and those that do spread to all parts of the brain. To date there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier disruption using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500 kHz spherical transducer ultrasound setup for use in the non-human primate. Here, we tested the accuracy of the system by targeting the caudate nucleus of the basal ganglia in two macaque monkeys. Our results show that average in-plane error of the system is on the order of 2 mm and targeting error in depth, i.e., along the ultrasound path, is even smaller averaging 1.2 mm. We have also developed a real-time treatment monitoring based on backscattered emissions spectral analyses. This technique helped us determining a safe and reliable acoustic parameters window for BBB opening.