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. 2020 Oct 6;10:16546. doi: 10.1038/s41598-020-73312-9

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© The Author(s) 2020

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Enhancement rate dynamics with FUS treatment during microbubble systemic clearance. (a–c) Systemic bolus injections of microbubble solutions with FUS treatment commencing immediately after injection. Representative MR images of FUS treated brains at points in the frontal cortex post (a) 3.3 µl/kg/min bolus and (b) 6.8 μl/kg/min bolus injections. (c) Plots of enhancement rate versus time post start of FUS treatment corresponding to images in (a,b). (d–f) Infusion clearance experiments where microbubbles were infused briefly and FUS treatment began immediately after infusion was stopped. Representative MR images of FUS treated brains at points in (d) hippocampus and (e) frontal cortex. (f) Plots of enhancement rate versus time after the start of FUS treatment corresponding to images in (d,e). *Average microbubble dosage rates are calculated as total volume of microbubble agent delivered over total treatment time. Points treated in frontal cortex are shown in blue, and rostral hippocampus in red. For each animal (represented by each trace in the plots) the total quantity of microbubbles delivered (in μl of equivalent undiluted agent) per kg is given. Dividing by total duration of FUS treatment yields a nominal bubble agent dose delivery per treatment time, permitting comparison to other experiments in this study. WL and WW of images have been adjusted as stated in “Methods” section.