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. 2021 May 27;26(11):6975–6991. doi: 10.1038/s41380-021-01129-7

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — A Schematic detail of the sonication procedure, indicating that the transducer sonicates a large area of the mouse brain during each treatment. B Schematic of the movement pattern of the transducer (black arrow). The start and end points are specified, and the transducer was scanned over the area in a raster grid pattern. A typical whole brain sonication used a 5 × 6 spot sonication pattern, covering virtually all of the cerebrum. Each mouse was rotated 180° for subsequent treatments. C To highlight the specificity of the sonication process, less than half of the brain was scanned using a 2 × 6 spot sonication path. The illustration shows a mouse brain following such a SUS^+MB sonication to regionally open the BBB, with Evans blue extravasation visualizing this scanning pattern. D The brain from (C) cut coronally in 1 mm sections, with the Evans blue staining showing that ultrasound penetrated through the entirety of the brain. E Representative temperature versus time plot for the sonication using a gray matter mimetic. Note the temperature rise beginning at ~40 s of the elapsed time (red arrow), and the rapid decline after the 6 s sonication ended (black arrow). F Average temperature change (ΔT °C) measured at the skull and with gray matter mimetic 6 s after sonication (n = 6, mean ± SD).