title: Pharmacokinetic analysis and drug delivery efficiency of the focused ultrasound-induced blood-brain barrier opening in non-human primates.
abstract: Focused Ultrasound (FUS) in conjunction with systemically administered microbubbles has been shown to open the Blood-Brain Barrier (BBB) locally, non-invasively and reversibly in rodents and non-human primates (NHP), suggesting the immense potential of this technique. The objective of this study entailed the investigation of the physiologic changes in the brain following the FUS-induced BBB opening and their relationship with the underlying anatomy.
  
  
  
  Pharmacokinetic analysis was implemented in NHP's that received FUS at various acoustic pressures. Relaxivity mapping enabled the robust quantitative detection of the BBB opening as well as grey and white matter segmentation. Drug delivery efficiency was measured for pre-clinical validation of the technique.
  
  
  
  Based on our results, the opening volume and the amount of the gadolinium delivered were found mostly contained in the grey matter, while FUS-induced permeability and drug concentration varied depending upon the underlying brain inhomogeneity, and increased with the acoustic pressure.
  
  
  
  Overall, apart from the in vivo protocols for BBB analysis developed here, this study also suggests the important role that FUS can have in efficient drug delivery via localized and transient BBB opening.
authors.affiliation: Department of Biomedical Engineering, Columbia University, Biomedical Engineering, 630 West 168th Street, Physicians and Surgeons 19-418, Manhattan, NY 10032, United States.
authors.forename: Gesthimani
authors.initials: G
authors.lastname: Samiotaki
authors.affiliation: Department of Biomedical Engineering, Columbia University, Biomedical Engineering, 630 West 168th Street, Physicians and Surgeons 19-418, Manhattan, NY 10032, United States. Electronic address: mek2204@columbia.edu.
authors.forename: Maria Eleni
authors.initials: ME
authors.lastname: Karakatsani
authors.affiliation: Department of Biomedical Engineering, Columbia University, Biomedical Engineering, 630 West 168th Street, Physicians and Surgeons 19-418, Manhattan, NY 10032, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Buch
authors.affiliation: Department of Biomedical Engineering, Columbia University, Biomedical Engineering, 630 West 168th Street, Physicians and Surgeons 19-418, Manhattan, NY 10032, United States.
authors.forename: Stephanos
authors.initials: S
authors.lastname: Papadopoulos
authors.affiliation: Department of Biomedical Engineering, Columbia University, Biomedical Engineering, 630 West 168th Street, Physicians and Surgeons 19-418, Manhattan, NY 10032, United States.
authors.forename: Shih Ying
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Radiology, Columbia University Medical Center, 177 Ft. Washington Ave. Milstein Bldg Room 3-124B, New York, NY 10032, United States.
authors.forename: Sachin
authors.initials: S
authors.lastname: Jambawalikar
authors.affiliation: Department of Biomedical Engineering, Columbia University, Biomedical Engineering, 630 West 168th Street, Physicians and Surgeons 19-418, Manhattan, NY 10032, United States; Department of Radiology, Columbia University Medical Center, 177 Ft. Washington Ave. Milstein Bldg Room 3-124B, New York, NY 10032, United States.
authors.forename: Elisa E
authors.initials: EE
authors.lastname: Konofagou
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D003287:Contrast Media / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D007089:Image Enhancement / Q000379:methods*; D008253:Macaca mulatta; D008297:Male; D045423:Microbubbles; D023421:Models, Animal; D014465:Ultrasonics / Q000379:methods*
chemical_list: D003287:Contrast Media; C064925:gadodiamide; D019786:Gadolinium DTPA
keywords: BBB opening; Concentration mapping; Focused ultrasound; Pharmacokinetics; Relaxometry