Small volume blood-brain barrier opening in macaques with a 1 MHz ultrasound phased array.

Autor: Manuel TJ; Vanderbilt University, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA., Sigona MK; Vanderbilt University, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA., Phipps MA; Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA., Kusunose J; Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA., Luo H; Vanderbilt University, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA., Yang PF; Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA., Newton AT; Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA., Gore JC; Vanderbilt University, Nashville, TN, USA; Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA., Grissom W; Vanderbilt University, Nashville, TN, USA; Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA., Chen LM; Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA., Caskey CF; Vanderbilt University, Nashville, TN, USA; Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Nashville, TN, USA. Electronic address: charles.f.caskey@vumc.org.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2023 Nov; Vol. 363, pp. 707-720. Date of Electronic Publication: 2023 Oct 17.
DOI: 10.1016/j.jconrel.2023.10.015
Abstrakt: The use of focused ultrasound to open the blood-brain barrier (BBB) has the potential to deliver drugs to specific regions of the brain. The size of the BBB opening and ability to localize the opening determines the spatial extent and is a limiting factor in many applications of BBB opening where targeting a small brain region is desired. Here we evaluate the performance of a system designed for small opening volumes and highlight the unique challenges associated with pushing the spatial precision of this technique. To achieve small volume openings in cortical regions of the macaque brain, we tested a custom 1 MHz array transducer integrated into a magnetic resonance image-guided focused ultrasound system. Using real-time cavitation monitoring, we demonstrated twelve instances of single sonication, small volume BBB opening with average volumes of 59 ± 37 mm 3 and 184 ± 2 mm 3 in cortical and subcortical targets, respectively. We found high correlation between subject-specific acoustic simulations and observed openings when incorporating grey matter segmentation (R 2  = 0.8577), and the threshold for BBB opening based on simulations was 0.53 MPa. Analysis of MRI-based safety assessment and cavitation signals indicate a safe pressure range for 1 MHz BBB opening and suggest that our system can be used to deliver drugs and gene therapy to small brain regions.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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