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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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Experimental timelines for standard infusion, bolus and microbubble clearance experiments conducted in this study. (a) A representative timeline of a standard infusion experiment, where the infusion is started prior to FUS to allow for an initial build-up of bubble volume in circulation and is continued throughout FUS in the treatment of sequential points. (b) In contrast, a representative timeline of a bolus experiment demonstrates the immediate start of FUS after bolus injection. During sonication, non-treatment periods were included to observe the effects of bubble clearance. (c) To further elucidate the differences in bubble clearance between bolus and infusion experiments, a clearance experiment protocol simulates a bolus injection with a pre-infusion period and the stoppage of infusion at the onset of FUS. Again, the inclusion of non-treatment periods within the treatment plan prolongs FUS, allowing for bubble clearance. All three experiment protocols finish with T2 and T1 pre and post contrast MR image collection.