title: Real-time, transcranial monitoring of safe blood-brain barrier opening in non-human primates.
abstract: 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.
authors: Departments of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors: Fabrice
authors: F
authors: Marquet
authors: Department of Neuroscience, Columbia University, New York, New York, United States of America.
authors: Tobias
authors: T
authors: Teichert
authors: Departments of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors: Shih-Ying
authors: SY
authors: Wu
authors: Departments of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors: Yao-Sheng
authors: YS
authors: Tung
authors: Departments of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors: Matthew
authors: M
authors: Downs
authors: Departments of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors: Shutao
authors: S
authors: Wang
authors: Departments of Biomedical Engineering, Columbia University, New York, New York, United States of America.
authors: Cherry
authors: C
authors: Chen
authors: Department of Neuroscience, Columbia University, New York, New York, United States of America.
authors: Vincent
authors: V
authors: Ferrera
authors: Departments of Biomedical Engineering, Columbia University, New York, New York, United States of America ; Department of Radiology, Columbia University, New York, New York, United States of America.
authors: Elisa E
authors: EE
authors: Konofagou
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000000981:diagnostic imaging*; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging*; D003287:Contrast Media / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D000882:Haplorhini; D006801:Humans; D008297:Male; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods*
chemical_list: D003287:Contrast Media