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 nonhuman 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.