Real-Time, Transcranial Monitoring of Safe Blood-Brain Barrier Opening in Non-Human Primates

PLoS One

Tobias Teichert¹  Vincent Ferrera¹  Matthew Downs²  Elisa E. Konofagou²  Fabrice Marquet²  Shih-Ying Wu²  Shutao Wang²  Yao-Sheng Tung²  Cherry Chen² 

[1] Department of Neuroscience, Columbia University, New York, New York, United States of America;Departments of Biomedical Engineering, Columbia University, New York, New York, United States of America

关键词: Sonication;    Drug delivery;    Monkeys;    Magnetic resonance imaging;    Skull;    Ultrasound imaging;    Acoustics;    Cavitation;   

DOI  :  10.1371/journal.pone.0084310

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

The delivery of drugs to specific neural targets faces two fundamental problems: (1) most drugs do not cross the blood-brain barrier, and (2) those that do, spread to the entire brain. To date, there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier (BBB) opening using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500-kHz spherical transducer ultrasound setup for targeted BBB opening in the non-human primate that does not require simultaneous MRI monitoring. So far, however, the targeting accuracy that can be achieved with this system has not been quantified systematically. In this paper, the accuracy of this system was tested by targeting caudate nucleus and putamen of the basal ganglia in two macaque monkeys. The average lateral targeting error of the system was ∼2.5 mm while the axial targeting error, i.e., along the ultrasound path, was ∼1.5 mm. We have also developed a real-time treatment monitoring technique based on cavitation spectral analysis. This technique also allowed for delineation of a safe and reliable acoustic parameter window for BBB opening. In summary, the targeting accuracy of the system was deemed to be suitable to reliably open the BBB in specific sub-structures of the basal ganglia even in the absence of MRI-based verification of opening volume and position. This establishes the method and the system as a potentially highly useful tool for brain drug delivery.

【 授权许可】

CC BY