title: Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring.
abstract: Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.
authors.forename: Shih-Ying
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.
authors.forename: Carlos Sierra
authors.initials: CS
authors.lastname: Sanchez
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.
authors.forename: Gesthimani
authors.initials: G
authors.lastname: Samiotaki
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.|Department of Neuroscience, Columbia University, New York, New York, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Buch
authors.affiliation: Department of Neuroscience, Columbia University, New York, New York, USA.
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Ferrera
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York, USA.|Department of Radiology, Columbia University, New York, New York, USA.
authors.forename: Elisa E
authors.initials: EE
authors.lastname: Konofagou
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D005682:Gadolinium / Q000493:pharmacokinetics / Q000494:pharmacology; D066128:Gray Matter / Q000098:blood supply* / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D000069453:Ultrasonic Waves
chemical_list: D005682:Gadolinium